Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as GSK1349572 (dolutegravir), GSK1349572 (Cohort I), GSK1349572 QD x 5 days, Dolutegravir
GSK1349572 · 52 trials · 11 indications
To Compare the proportion of participants with HIV-1 virologic suppression at 28 weeks of HIV treatment by arm.
Participants with HIV-1 RNA \>= 50 c/mL were evaluated. Virologic outcome was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the Week 48 Window. The analysis was done using the modified Snapshot algorithm.
Number of participants with plasma HIV 1 RNA \>=50 c/mL were evaluated using FDA snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA \>=50 c/mL were termed as subjects with virologic failure. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
Participants were classified as "HIV-1 RNA \<50 c/mL" using an ITT-E missing = Failure analysis. Participants were classified as 'HIV-1 RNA \< 50 c/mL' if the last viral load within the Week 24 visit window was \<50/c/mL, regardless of the ART regimen they were on at the time of viral load assessment (in other words switch from DTG plus 3TC fixed-dose combination \[FDC\] to another ART was not penalized) and as HIV-1 RNA \>= 50 c/mL in all other cases (i.e. last viral load within Week 24 visit window \>= 50 c/mL, on study but having missing viral load data at Week 24, discontinued early from study due to lost to follow-up (LFU), withdrew consent or any other reason). Confidence intervals (CI) were calculated based on the Exact Clopper-Pearson method. Percentage of participants with plasma HIV-1 RNA \< 50 c/mL based on ITT-E missing = Failure analysis at Week 24 are presented.
Percentage of participants with plasma HIV-1 RNA \<50 c/mL was assessed at Week 48 according to the Food and Drug Administration (FDA) snapshot algorithm.
Percentage of participants with virologic failure (plasma HIV-1 RNA \>=50 c/mL) was evaluated using FDA snapshot algorithm at Week 48. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest. Intent-to-treat exposed (ITT-E) Population comprises of all randomized participants who received at least one dose of study treatment either DTG + 3TC or TBR. Participants were assessed according to the treatment to which the participant was randomized. Any participant receiving a treatment randomization number was considered to be randomized.
Percentage of participants with HIV-1 RNA\<50 c/mL was obtained using Food and Drug Administration (FDA) Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel (CMH) weights. Intent-To-Treat Exposed (ITT-E) Population was used which comprised of all randomized participants who received at least one dose of study treatment. Percentage values are rounded to the nearest whole digit.
Percentage of participants with plasma HIV 1 RNA \< 50 c/mL at Week 48 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to demonstrate the non-inferior antiviral activity of switching to DTG+RPV once daily compared to continuation of CAR over 48 weeks in HIV-1 infected antiretroviral therapy (ART)-experienced participants. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest. Plasma samples were collected for quantitative analysis of HIV-1 RNA.
Plasma samples were collected for quantitative analysis of HIV-1 RNA. The percentage of participants with plasma HIV-1 RNA \<50 copies/milliliter was assessed at Week 48 using the snapshot algorithm in the DTG arm. Response was assessed using a modified FDA Snapshot algorithm in which participants were not penalized for any single protocol allowed background therapy substitution even if occurs after the first trial visit. In this approach participants with HIV-1 RNA \>=50 copies/milliliter are considered as non-responders. Participants without HIV-1 RNA data at Week 48 (due to missing data or discontinuation of investigational product \[IP\] prior to visit window) are also considered as non-responders, as well as participants with anti-retroviral (ART) substitutions were not permitted. Study drug (i.e. DTG or EFV) was not allowed to be substituted.
Blood samples were collected at indicated timepoints for Pharmacokinetic (PK) analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
Blood samples were collected for analysis of hemoglobin. Any abnormality was graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Number of participants (Pregnant Women) with maximum severity of post-Baseline emergent toxicities with respect to hemoglobin has been presented.
Blood samples were collected for the analysis of chemistry parameters including ALT and AST.
Blood samples were collected for the analysis of chemistry parameters including ALT and AST. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Blood samples were collected for the analysis of chemistry parameters including Bilirubin and Creatinine.
Blood samples were collected for the analysis of chemistry parameters including Bilirubin and Creatinine. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Blood samples were collected for the analysis of hematology parameters including hemoglobin.
Blood samples were collected for the analysis of hematology parameters including hemoglobin. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Blood samples were collected for the analysis of hematology parameters including leukocytes and platelets.
Blood samples were collected for the analysis of hematology parameters including leukocytes and platelets. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment. Number of participants (pregnant women) who discontinued the treatment due to adverse events have been presented.
Data for participants (pregnant women) demonstrated congenital malformations was reported.
Number of participants (pregnant women) with adverse events (AE) as per severity grades were presented. Grade 1 is mild, grade 2 is moderate, grade 3 is severe or medically significant but not immediately life-threatening and grade 4 is life-threatening consequences; urgent intervention required.
Percentage of participants with plasma HIV 1 RNA \<50 c/mL at Week 48 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to demonstrate the non-inferior activity of DTG plus 2 NRTI's compared to LPV/RTV plus 2 NRTI's. Analysis was performed on Intent-to-treat exposed (ITT-E) Population, which comprised of all randomized participants who received at least one dose of study medication. Percentage values are rounded off.
Percentage of participants with plasma human immunodeficiency virus type 1(HIV-1) ribonucleic acid (RNA) \<50 copies per milliliter (c/mL) were assessed at Week 48 using the Snapshot algorithm. Analysis was performed using a stratified analysis with Cochran-Mantel-Haenszel (CMH) weights, adjusting for Baseline plasma HIV-1 RNA ( =\<vs. \>100,000 c/mL) and CD4+ cell count (=\<350 cells per millimeter cube (cells/mm\^3) or \>350 cells/mm\^3). Intent-to-Treat Exposed (ITT-E) Population comprised of all randomized participants who received at least one dose of study medication. Percentage values are rounded off.
Cerebrospinal fluid (CSF) is a clear, colorless bodily fluid produced in the choroid plexus of the brain. The CFS samples were collected at the Week 2 and Week 16 visits, within 1 hour of plasma pharmacokinetic (PK) sampling. The ratio (presented as a percentage) of CSF DTG concentration over paired plasma total DTG concentration (RCSF\_plasma) was calculated at the Week 2 and Week 16 visits.
Total plasma DTG concentrations were calculated at the Week 2 and Week 16 visits.
Unbound (free, not bound to cellular proteins) plasma DTG concentrations were calculated at the Week 2 and Week 16 visits.
The unbound fraction of DTG in plasma (presented as a percentage of unbound \[i.e., free DTG not bound to cellular proteins\] DTG plasma concentration over paired plasma total DTG concentration) was calculated at the Week 2 and Week 16 visits.
CSF is a clear, colorless bodily fluid produced in the choroid plexus of the brain. The CFS samples were collected at the Week 2 and Week 16 visits, within 1 hour of plasma PK sampling. DTG concentration in CSF were calculated at the Week 2 and Week 16 visits.
Mean change from Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 8 was calculated as the Day 8 value minus the Baseline value. The last observation was carried forward if a participant had missed the Day 8 visit. The Baseline observation was carried forward if a participant had discontinued the treatment before Day 8. Blood samples for assessment of HIV-1 RNA levels were collected at Baseline and Day 8.
The number of participants who had viral load \<50 copies/mL at Week 24 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI \[due to missing data/discontinuation of investigational product prior to the visit window\]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the VOI analysis window.
The number of participants who had viral load \<50 copies/mL at Week 48 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI \[due to missing data/discontinuation of investigational product prior to the visit window\]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the VOI analysis window.
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury.
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. AE/SAE severity was graded according to the DAIDS grading scale. The DAIDS displays events as Grades 1-4 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, potentially life threatening.
The severity of clinical chemistry toxicities was graded according to the DAIDS toxicity scale. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity.
The severity of hematology toxicities was graded according to the DAIDS. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity.
The percentage of participants with plasma HIV-1 RNA \<50 c/mL at Week 48 was assessed. Plasma samples were collected for the quantitative assessment of HIV-1 RNA based on the Missing, Switch, or Discontinuation equals Failure (MSDF) algorithm,as codified by the Food and Drug Administration's Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigationl product prior to the visit window) as non-responders, as well as participants who switched their concomitant antiretroviral therapy (ART) in certain scenarios. Since changes in ART were not permitted in this protocol, all such participants who changed ART were to be considered non-responders. Otherwise, virologic success or failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the visit of interest window.
The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) \<50 c/mL at Week 48 was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the randomized phase of the study.
Percentage of participants with plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) with \<50 c/mL was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) snapshot algorithm. The algorithm treats all participants without HIV-1 RNA data as non-responders, as well as participants who switch their concomitant Antiretroviral Therapy (ART) prior to Week 48 as follows: background ART substitutions not permitted per study; background ART substitutions permitted per study unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure will be determined by the last available HIV-1 RNA assessment while the subject was on-treatment. Intent-to-Treat Exposed (ITT-E) Population comprised all randomized participants who received at least one dose of study medication.
There were eight participants with no data at week 48: one LTFU, one protocol deviation (M184V at screening), two investigator decision (1 lung cancer, 1 M184V mutation detected in plasma RNA population genotyping at transient rebound, suppressed with dolutegravir/lamivudine not fulfilling criteria for virologic withdrawal), one consent withdrawal and three withdrawals for AEs. It was pre-specified to report all participants who discontinued with last available HIV-1 RNA ≥50 copies/mL in "Number of Participants with HIV-1 RNA ≥50 copies/mL" category at week 48.
The number of participants who acheived Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) \<400 c/mL or at least 0.7 log10 c/mL below their Baseline value at Day 11 was assessed. The last observation was carried forward if a participant had missed the Day 11 visit. The Baseline observation was carried forward if a participant had discontinued the treatment before Day 11. Blood samples for assessment of HIV-1 RNA levels were collected at Baseline and Day 11.
Plasma samples were collected for quantitative HIV-1 RNA analysis at Week 16. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (\<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason. Data are reported per the Week 16 report. In later cuts of the data, the Week 16 values may have changed (because of the nature of the TLOVR algorithm).ITT-E Population included all randomized participants who received at least one dose of study medication
Change from Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) was calculated as the Day 11 value minus the Baseline value. Blood samples for the measurement of HIV-1 RNA levels were obtained throughout the treatment period (Day 1 to Day 11).
AUC is defined as the area under the GSK1349572 concentration-time curve as a measure of drug exposure. AUC(0-inf) is defined as the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time. AUC(0-24) is defined as the area under the concentration-time curve from time zero (pre-dose) to24 hours. Blood samples for pharmacokinetic (PK) analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Cmax is defined as the maximum observed plasma concentration, and C24 is defined as the concentration at 24 hours post dose. Blood samples for PK analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration. From the plasma concentration-time curve, Cmax was determined by standard non-compartmental analysis using WinNonlin Pro 4.1 or higher.
tmax is defined as the time to the maximum obsevered plasma concentration. Absorption lag time is defined as the time taken for a drug to appear in the systemic circulation following administration. tlag was estimated based on PK sampling times of 0 (pre-dose), 0.5, 1, 1.5, 2 3, 4, 6, 8, 12, and 24 hours post-dose. Blood samples for PK analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration. From the plasma concentration-time curve, tmax was determined by standard non-compartmental analysis using WinNonlin Pro 4.1 or higher.
The terminal half-life (t1/2) of GSK1349572 is defined as the time required for the plasma concentration of GSK1349572 to reach half of its original concentration. Blood samples for PK analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
The CL/F is defined as the apparent total clearance of the drug from plasma after oral administration. Blood samples for PK analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
AUC is defined as the area under the GSK1349572 concentration-time curve as a measure of drug exposure. AUC(0-tau) is defined as the area under the concentration-time curve over the dosing interval. Blood samples for PK analysis of GSK1349572 were obtained on Day 10at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
C0 is defined as the pre-dose concentration. Ctau is defined as the concentration at the end of the dosing interval. Cmin is defined as the minimum observed concentration during one dosing interval. Cmax is defined as the maximum obsevered plasma concentration. Blood samples for PK analysis of GSK1349572 were obtained on Day 10 at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
tmax is defined as the time to the maximum obsevered plasma concentration. Blood samples for PK analysis of GSK1349572 were obtained on Day 10 at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration. From the plasma concentration-time curve, tmax was determined by standard non-compartmental analysis using WinNonlin Pro 4.1 or higher.
The terminal half-life (t1/2) of GSK1349572 is defined as the time required for the plasma concentration of GSK1349572 to reach half of its original concentration. Blood samples for PK analysis of GSK1349572 were obtained on Day 10 at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
The CL/F is defined as the apparent total clearance of the drug from plasma after oral administration. Blood samples for PK analysis of GSK1349572 were obtained on Day 10 at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Concomitant medications received during the study period are presented by generic term. Only those concomitant medications that were received by at least two participants are presented. "Multiple ingredient" is the term used in the statistical package for items that contain more than one active ingredient.
Blood pressure measurement included systolic blood pressure (SBP) and diastolic BP (DBP). Change in the mean blood pressure from Baseline was calculated as the post-Baseline value minus the Baseline value. Data are presented for change from Baseline at Day 1 (2 hours post dose \[hrs\]), Day 4 (1 hr pre-dose), Day 7 (1 hr pre-dose), and Day 10 (1 hr pre-dose and 2 hrs post dose).
Heart rate is the measure of heart beats per minute (bpm). Change in the mean heart rate from Baseline was calculated as the post-Baseline value minus the Baseline value. Data are presented for change from Baseline at Day 1 (2 hours post dose \[hrs\]), Day 4 (1 hr pre-dose), Day 7 (1 hr pre-dose), and Day 10 (1 hr pre-dose and 2 hrs post dose).
A 12-lead electrocardiogram (ECG) was performed by qualified personnel at the site after the participant had rested for at least 5 minutes in a semi-recumbent or supine position. If a QTc measurement of \>=500 milliseconds (msec) was noted on a scheduled or unscheduled ECG, two additional ECGs were to be obtained within 5 minutes to confirm the abnormality. The number of participants with abnormal clinically significant (CS) and not clinically significant (NCS) ECG findings are presented here. The site determined if an ECG finding is significant or not. ECGs were obtained at Screening, Day 1 (pre-dose \[twice\] and then 1.0, 1.5, and 2.0 hours \[hrs\] post dose), Day 4 (pre-dose), Day 7 (pre-dose), Day 10 (pre-dose and then 1.0, 1.5, and 2.0 hrs post dose), Day 11 (prior to the 24 hr PK sample \[pre lab\]), and Follow-up.
Clinical laboratory toxicities were graded according to the National Institutes of Allergy and Infectious Diseases (NIAID), Division of Acquired Immunodeficiency Syndrome (DAIDS). Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented only for Grade 3 and Grade 4 laboratory abnormalities. Clinical laboratory abnormalities included: increased glucose, lipase, decreased platelets, and triglycerides.
Blood samples were collected at indicated time points to study the pharmacokinetic (PK) profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of monolayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 1.
Blood samples were collected at given time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted conditions in Periods 1 and 2 of Part 2.
Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of monolayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 1.
Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2.
Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of monolayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 1.
Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2.
Blood samples will be collected at pre-dose and at specific post-dose time points for calculating AUC \[0- infinity\]
Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax
Serial blood samples for pharmacokinetic (PK) analysis of DTG will be collected. From the plasma concentration-time data, the PK parameters will be determined.
Serial blood samples for PK analysis of DTG will be collected. From the plasma concentration-time data, the PK parameters will be determined.
Serial blood samples for PK analysis of 3TC will be collected. From the plasma concentration-time data, the PK parameters will be determined.
Serial blood samples for PK analysis of 3TC will be collected. From the plasma concentration-time data, the PK parameters will be determined.
PK parameters will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC \[0-Infinity\]), maximum observed concentration (Cmax) and apparent oral clearance (CL/F)
PK parameters will include AUC (0-Infinity), Cmax and CL/F
PK parameters will include AUC (0-Infinity), Cmax and CL/F
Plasma PK parameters for DTG include steady state area under the concentration-time curve over the dosing interval (AUC (0-tau)), maximum observed concentration (Cmax), concentration at the end of the dosing interval (Ctau), apparent clearance following oral dosing (CL/F) and terminal phase half-life (t1/2) , following DTG 50 mg q24h administration with and without DCV 60mg q24h
Plasma DCV steady state AUC(0-tau), Cmax, Ctau, CL/F and t1/2 following administration of DCV 60 mg q24h with and without DTG 50 mg q24h
PK parameters will include: Steady state plasma DTG concentration at the end of the dosing interval (Ctau), maximum concentration (Cmax), area under the time-concentration curve over the dosing interval \[AUC(0-tau)\], apparent clearance following oral dosing (CL/F), terminal phase half life (t1/2), concentration at time zero (C0) and minimum concentration (Cmin)
To evaluate the single dose PK of DTG, area under the concentration-time curve from time zero to last time of quantifiable concentration (AUC \[0-t\]) and area under the concentration-time curve from time zero extrapolated to infinite time (AUC (0-infinity) will be assessed with DTG given alone and when given with Calcium Carbonate (co-administered in fed or fasted state or 2 hours (hrs) separation, fasted) or Ferrous Fumarate (co-administered in fed or fasted state or 2 hrs separation, fasted)
To evaluate the single dose PK of DTG, maximum observed concentration (Cmax) and concentration at 24 hours post-dose (C24) will be assessed with DTG given alone and when given with Calcium Carbonate (co-administered in fed or fasted state or 2 hrs separation, fasted) or Ferrous Fumarate (co-administered in fed or fasted state or 2 hrs separation, fasted)
Plasma PK samples will be collected pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post- dose.
Samples will be collected at predose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose
Steady state total and R-methadone PK measure: AUC (0-t), Cmax and Ct.
Samples will be collected at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 10 and 21
Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC(0-tau)), Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax), Pre-dose (trough) concentration at the end of the dosing interval (Ctau)
steady state, AUC(0-t), Cmax, tmax, and Ctau
steady state, AUC(0-tau), Cmax, tmax, and Ctau
AUC(0-tau), Cmax, tmax, and Ctau
Samples will be collected at predose and 1, 2, 3, 4, 8, 12 and 24 hours post dose
Plasma GSK1349572 PK parameters: AUC(0-24), Cmax, and C24, and dose-normalized AUC(0-24), Cmax, and C24 following single dose administration of 100mg and 50mg.
Plasma GSK1349572 PK parameters: AUC(0-24), Cmax, and C24, and dose-normalized AUC(0-24), Cmax, and C24 following single dose administration of 100mg and 50mg.
Plasma GSK1349572 PK parameters: AUC(0-24), Cmax, and C24, and dose-normalized AUC(0-24), Cmax, and C24 following single dose administration of 100mg and 50mg.
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
| Arm | Type | Description |
|---|---|---|
| Arm 1: DTG 50 mg/ 3TC 300mg (Dovato®) twice daily (BID) | EXPERIMENTAL | Arm 1: DTG 50mg/3TC 300 mg fixed-dose-combination (FDC) tablet (Dovato®) twice daily during TB therapy and for 2 weeks after, then DTG 50mg/3TC 300 mg FDC tablet (Dovato®) once daily to week 52 |
| Arm 2: DTG 50 mg/ 3TC 300mg (Dovato®) once daily (QD) in the morning with DTG 50 mg in the evening | EXPERIMENTAL | Arm 2: DTG 50mg/300mg FDC tablet plus DTG 50mg at night during TB treatment and for 2 weeks after, then DTG 50 mg/ 3TC 300 mg FDC tablet (Dovato®) once daily to week 52 |
| Arm 3: Standard of Care 3-drug ART (DTG+ TDF/3TC) plus DTG 50mg in the evening. | ACTIVE_COMPARATOR | Arm 3: Local Standard of Care 3-drug ART (DTG 50mg + TDF/3TC) plus DTG 50 mg at night during TB treatment and for 2 weeks after, then DTG 50 mg + TDF/3TC FDC tablet once daily to week 52 |
| DTG/3TC | EXPERIMENTAL | Participants will receive FDC of DTG/3TC once daily until Week 96. |
| BIC/FTC/TAF | ACTIVE_COMPARATOR | Participants will receive BIC/FTC/TAF once daily until Week 96. |
| Participants Receiving Dolutegravir/Lamivudine (DTG/3TC) Fixed-dose combination (FDC) | EXPERIMENTAL | Participants living with HIV switched from Bictegravir/Emtricitabine/Tenofovir alafenamide (BIC/FTC/TAF) on Day 1 and received once daily dose of DTG/3TC FDC for 96 weeks. At Week 96, all participants switched to locally available DTG/3TC FDC or local standard of care (SOC) Antiretroviral Therapy (ART). |
| Participants Receiving DTG/3TC Fixed Dose Combination (FDC) | EXPERIMENTAL | - |
| Participants Receiving CAB + RPV LA | EXPERIMENTAL | - |
| Participants receiving DTG/3TC FDC | EXPERIMENTAL | Eligible participants will be randomized to receive 50 milligrams (mg)/300 mg DTG/3TC FDC therapy from Day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase. |
| Participants receiving CAR | ACTIVE_COMPARATOR | Eligible participants will continue to receive CAR from Day 1 up to 52 weeks. |
| Participants receiving Dolutegravir + Lamivudine FDC | EXPERIMENTAL | Participants will receive DTG 50mg and 3TC 300 mg FDC tablet orally once daily (OD) with or without food |
| DTG/3TC FDC | EXPERIMENTAL | Participants received dolutegravir/lamivudine (DTG/3TC) (50/300 mg) Fixed Dose Combination (FDC) tablets orally once daily. |
| DTG + 3TC 50 mg/300 mg | EXPERIMENTAL | Participants will receive a single tablet of a two-drug regimen of DTG 50 mg + 3TC 300 mg once daily from Day 1 through Week 200 (Early and Late Switch Phase). |
| TAF based regimen (TBR) | ACTIVE_COMPARATOR | Participants will continue their TBR from Day 1 to Week 148 (Early Switch Phase), and eligible participants will switch to DTG + 3TC once daily from Week 148 to 200 (Late Switch Phase). |
| DTG + 3TC (50 mg+300 mg) | EXPERIMENTAL | Eligible participants will receive one 50 mg tablet of DTG plus one overencapsulated 300 mg 3TC tablet orally once daily upto 96 weeks; thereafter will receive DTG plus 3TC tablet upto Week 148 and will continue to receive this schedule until (i) DTG and 3TC are both locally approved for use as part of a dual regimen, and the single entities of DTG and 3TC are available to patients (e.g. through public health services), or (ii) the DTG/3TC FDC tablet, if required by local regulations, is available, , or (iii) the participant no longer derives clinical benefit, or (iv) the participant meets a protocol defined reason for discontinuation, or (v) development of the DTG plus 3TC dual regimen is terminated. |
| DTG + TDF/FTC FDC (50 mg+300/200 mg) | ACTIVE_COMPARATOR | Eligible participants will receive one 50 mg tablet of DTG plus one overencapsulated TDF/ FTC FDC (300/200 mg) tablet orally once daily upto 96 weeks; thereafter will receive DTG plus TDF/FTC FDC tablets upto Week 148 (open-label randomised phase). |
| DTG + 3TC (50 mg+300 mg | EXPERIMENTAL | Eligible participants will receive one 50 mg tablet of DTG plus one overencapsulated 300 mg 3TC tablet orally once daily upto 96 weeks; thereafter will receive DTG plus 3TC tablet upto Week 148 and will continue to receive this schedule until (i) DTG and 3TC are both locally approved for use as part of a dual regimen, and the single entities of DTG and 3TC are available to patients (e.g. through public health services), or (ii) the DTG/3TC FDC tablet, if required by local regulations, is available, , or (iii) the participant no longer derives clinical benefit, or (iv) the participant meets a protocol defined reason for discontinuation, or (v) development of the DTG plus 3TC dual regimen is terminated. |
| Current antiretroviral regimen (CAR) | ACTIVE_COMPARATOR | Participants continued to receive their current antiretroviral regimen (two nucleoside reverse transcriptase inhibitor \[NRTIs\] + a third agent). A third agent included either an: integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). CAR was administered according to the approved labeling in an open-label fashion up to Week 52 during early switch phase. At Week 52, participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) \<50 copies per milliliter (c/mL), switched to DTG 50 mg + RPV 25 mg once daily and were followed-up through the Late Switch Phase, at Week 148 and through the Continuation Phase, after Week 148. |
| DTG + RPV | EXPERIMENTAL | Participants received DTG 50 milligrams (mg) + RPV 25 mg together once daily at approximately the same time, with a meal, in an open-label fashion up to Week 52 during early switch phase. Participants continued to receive DTG 50 mg + RPV 25 mg up to Week 148 during the Late Switch Phase. Participants who successfully completed 148 weeks of treatment were given the opportunity to continue to receive DTG + RPV once daily in the Continuation Phase (after Week 148). |
| Dolutegravir | EXPERIMENTAL | Twice-daily DTG 50 mg plus dual NRTI during RIF-containing TB treatment (isoniazid, RIF, pyrazinamide and ethambutol standard doses by the NTP under program conditions or acceptable alternative RIF-containing regimens) and for 2 weeks following discontinuation of TB treatment, then once-daily DTG 50 mg with the same NRTI through Week 52 |
| Efavirenz | ACTIVE_COMPARATOR | Once-daily EFV 600 mg plus dual NRTI through Week 52 along with TB treatment including isoniazid, RIF, pyrazinamide and ethambutol standard doses by the NTP under program conditions. |
| DTG/ABC/3TC | EXPERIMENTAL | All subjects will be administered DTG 50 milligrams (mg)/ABC 600 mg/3TC 300 mg FDC tablet once daily, with or without food. |
| DTG arm | EXPERIMENTAL | Subjects will receive one oral tablet of 50 mg DTG once daily plus two NRTIs selected by the investigator |
| LPV/RTV arm | ACTIVE_COMPARATOR | Subjects will receive four oral tablets of200/50 mg LPV/RTV once daily or two oral tablets of 200/50 mg LPV/RTV twice daily plus two NRTIs selected by the investigator |
| DTG/ABC/3TC FDC | EXPERIMENTAL | As per the randomization schedule subjects will be administered with DTG/ABC/3TC (50mg/600mg/300mg) FDC tablet OD up to Week 48 and if continued if applicable in the Continuation Phase. DTG/ABC/3TC FDC may be administered with or without food |
| ATV +RTV +TDF/FTC FDC | ACTIVE_COMPARATOR | As per the randomization schedule subjects will be administered with ATV (300mg capsule) +RTV (100mg tablet) + TDF/FTC (300mg/200mg tablet) FDC OD up to Week 48. ATV+RTV+ TDF/FTC FDC must be taken with food |
| Dolutegravir 50mg Once Daily | EXPERIMENTAL | All subjects will receive 50mg dolutegravir once daily in combination with background antiretroviral therapy consisting of one abacavir/lamivudine fixed dose combination tablet once daily |
| Dolutegravir (N=~394): | EXPERIMENTAL | Dolutegravir 50mg once daily + abacavir/lamivudine as the fixed-dose combination once daily + Atripla placebo once daily |
| Atripla (N=~394): | ACTIVE_COMPARATOR | Atripla once daily + Dolutegravir placebo once daily + abacavir/lamivudine as the fixed-dose combination placebo once daily |
| GSK1349572 + Raltegravir Placebo | EXPERIMENTAL | Subjects will receive GSK1349572 50mg once daily plus raltegravir placebo twice daily. |
| Raltegravir + GSK1349572 Placebo | ACTIVE_COMPARATOR | Subjects will receive raltegravir 400mg twice daily plus GSK1349572 placebo once daily. |
| GSK1349572 (N=~394) | EXPERIMENTAL | GSK1349572 50mg once daily + raltegravir placebo twice daily + NRTI background therapy once daily |
| raltegravir (N=~394) | ACTIVE_COMPARATOR | raltegravir 400mg twice daily + GSK1349572 placebo once daily + NRTI background therapy once daily |
| Dovato (Dolutegravir+lamivudine) | EXPERIMENTAL | Treatment: Dolutegravir 50 mg/Lamivudine 300 mg, one film coated-tablet once daily during 96 weeks |
| GSK1349572 Cohort I | EXPERIMENTAL | Single Arm, Cohort I |
| GSK1349572 Cohort II | EXPERIMENTAL | Single Arm, Cohort II |
| 10 mg GSK1349572 | EXPERIMENTAL | subjects will receive GSK1349572 10mg once daily blinded to dose |
| 25mg GSK1349572 | EXPERIMENTAL | subjects will receive GSK1349572 25mg once daily blinded to dose |
| 50mg GSK1349572 | EXPERIMENTAL | subjects will receive GSK1349572 50mg once daily blinded to dose |
| efavirenz control | OTHER | efavirenz will serve as the internal control arm |
| Treatment A | EXPERIMENTAL | GSK1349572 2 mg or placebo every 24 hours for 10 days. Screening visit up to 30 days prior to first dose and follow-up for 11 days after last dose. |
| Treatment B | EXPERIMENTAL | GSK1349572 10 mg or placebo every 24 hours for 10 days. Screening visit up to 30 days prior to first dose and follow-up for 11 days after last dose. |
| Treatment C | EXPERIMENTAL | GSK1349572 50 mg or placebo every 24 hours for 10 days. Screening visit up to 30 days prior to first dose and follow-up for 11 days after last dose. |
| Dolutegravir(DTG)/Rilpivirine (RPV) | EXPERIMENTAL | - |
| Treatment sequence A/B: Part 1 | EXPERIMENTAL | Eligible subjects will be randomized in sequence A/B and will receive A: DTG 50 milligram (mg) and 3TC 300 mg single entities in Period 1, B: DTG 3TC FDC formulation 1 tablet in Period 2. |
| Treatment sequence B/A: Part 1 | EXPERIMENTAL | Eligible subjects will be randomized in sequence B/A and will receive B: DTG 3TC FDC formulation 1 tablet in Period 1 and A: DTG 50 mg and 3TC 300 mg single entities in Period 2. |
| Subjects receiving high fat meal: Part 1 | EXPERIMENTAL | Eligible subjects will be administered single dose of DTG 3TC FDC formulation 1 tablet with high fat meal in Period 3 to study the effect of food on tablet. |
| Treatment sequence A/C: Part 2 | EXPERIMENTAL | Eligible subjects will be randomized in sequence A/B and will receive A: DTG 50 mg and 3TC 300 mg single entities in Period 1 and C: DTG 3TC FDC formulation 2 tablet in Period 2. |
| Treatment sequence C/A: Part 2 | EXPERIMENTAL | Eligible subjects will be randomized in sequence C/A and will receive C: DTG 3TC FDC formulation 2 tablet in Period 1 and A: DTG 50 milligram (mg) and 3TC 300 mg single entities in Period 2. |
| Subjects receiving high fat meal: Part 2 | EXPERIMENTAL | Eligible subjects will be administered single dose of DTG 3TC FDC formulation 2 tablet with high fat meal in Period 3 to study the effect of food on tablet. |
| SEQUENCE ABCDE | EXPERIMENTAL | Participants will receive treatment A in period 1, treatment B in period 2, treatment C in period 3, treatment D in period 4 and treatment E in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with zero mineral content (ZMC) water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 milliliter (mL) stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 minutes(mins), re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. |
| SEQUENCE BCDEA | EXPERIMENTAL | Participants will receive treatment B in period 1, treatment C in period 2, treatment D in period 3, treatment E in period 4 and treatment A in period 5 (one treatment per period). Where A= EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. |
| SEQUENCE CDEAB | EXPERIMENTAL | Participants will receive treatment C in period 1, treatment D in period 2, treatment E in period 3, treatment A in period 4 and treatment B in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. |
| SEQUENCE DEABC | EXPERIMENTAL | Participants will receive treatment D in period 1, treatment E in period 2, treatment A in period 3, treatment B in period 4 and treatment C in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. |
| SEQUENCE EABCD | EXPERIMENTAL | Participants will receive treatment E in period 1, treatment A in period 2, treatment B in period 3, treatment C in period 4 and treatment D in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. |
| DTG/RPV FDC-DTG plus RPV | EXPERIMENTAL | Subjects will receive a single oral dose of DTG/RPV 50 mg/25 mg FDC tablet in Period 1 under fed state. After a washout period of at least 21 days, subjects will receive a single oral dose of separate tablet formulations of DTG 50 mg and RPV 25 mg together in Period 2 under fed state. |
| DTG plus RPV-DTG/RPV FDC | EXPERIMENTAL | Subjects will receive a single oral dose of separate tablet formulations of DTG 50 mg and RPV 25 mg together in Period 1 under fed state. After a washout period of at least 21 days, subjects will receive a single oral dose of DTG/RPV 50 mg/25 mg FDC tablet in Period 2 under fed state. |
| Treatment Sequence ABC | EXPERIMENTAL | Subject will receive reference treatment DTG 50mg and 3TC 300mg administered as single entity tablets (treatment A) in period 1, experimental Dolutegravir/Lamivudine 50 mg/300 mg FDC tablet (Product Code AA, treatment B) in period 2 and experimental Dolutegravir/Lamivudine 50 mg/300 mg FDC tablet (Product Code AB, treatment C) in period 3 in a fasted state. There will be at least 7 days washout between dosing periods. |
| Treatment Sequence BCA | EXPERIMENTAL | Subject will receive experimental Dolutegravir/Lamivudine 50 mg/300 mg FDC tablet (Product Code AA, treatment B) in period 1 and experimental Dolutegravir/Lamivudine 50 mg/300 mg FDC tablet (Product Code AB, treatment C) in period 2 and reference treatment DTG 50mg and 3TC 300mg administered as single entity tablets (treatment A) in period 3 in a fasted state. There will be at least 7 days washout between dosing periods. |
| Treatment Sequence CAB | EXPERIMENTAL | Subject will receive experimental Dolutegravir/Lamivudine 50 mg/300 mg FDC tablets (Product Code AB, treatment C) in period 1 and reference treatment DTG 50mg and 3TC 300mg administered as single entity tablets (treatment A) in period 2 and experimental Dolutegravir/Lamivudine 50 mg/300 mg FDC tablets (Product Code AA, treatment B) in period 3 in a fasted state. There will be at least 7 days washout between dosing periods. |
| Treatment Sequence ACB | EXPERIMENTAL | Subject will receive reference treatment DTG 50mg and 3TC 300mg administered as single entity tablets (treatment A) in period 1, experimental Dolutegravir/Lamivudine 50 mg/300 mg FDC tablets (Product Code AB, treatment C) in period 2 and experimental Dolutegravir/Lamivudine 50 mg/300 mg FDC tablets (Product Code AA, treatment B) in period 3 in a fasted state. There will be at least 7 days washout between dosing periods. |
| Treatment Sequence BAC | EXPERIMENTAL | Subject will receive experimental Dolutegravir/Lamivudine 50 mg/300 mg FDC tablets (Product Code AA, treatment B) in period 1 and reference treatment DTG 50mg and 3TC 300mg administered as single entity tablets (treatment A) in period 2 and experimental Dolutegravir/Lamivudine 50 mg/300 mg FDC tablets (Product Code AB, treatment C) in period 3 in a fasted state. There will be at least 7 days washout between dosing periods. |
| Treatment Sequence CBA | EXPERIMENTAL | Subject will receive experimental Dolutegravir/Lamivudine 50 mg/300 mg FDC tablets (Product Code AB, treatment C) in period 1 and experimental Dolutegravir/Lamivudine 50 mg/300 mg FDC tablets (Product Code AA, treatment B) in period 2 and reference treatment DTG 50mg and 3TC 300mg administered as single entity tablets (treatment A) in period 3 in a fasted state. There will be at least 7 days washout between dosing periods. |
| Part 1 Cohort 1- Sequence 1 | EXPERIMENTAL | Each subject will receive a single dose of Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet), Treatment B (DTG/RPV 50 mg/25 mg: Product Code AS) and Treatment C (DTG/RPV 50 mg/25 mg: Product Code AM) in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. All treatments will be administered in fed state. |
| Part 1 Cohort 1- Sequence 2 | EXPERIMENTAL | Each subject will receive a single dose of Treatment D (DTG/RPV 50 mg/25 mg: Product Code AQ), Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet) and Treatment B (DTG/RPV 50 mg/25 mg: Product Code AS) in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. All treatments will be administered in fed state. |
| Part 1 Cohort 1- Sequence 3 | EXPERIMENTAL | Each subject will receive a single dose of Treatment B (DTG/RPV 50 mg/25 mg: Product Code AS), Treatment E (DTG/RPV 50 mg/25 mg: Product Code AK) and Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet) in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. All treatments will be administered in fed state. |
| Part 1 Cohort 1- Sequence 4 | EXPERIMENTAL | Each subject will receive a single dose of Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet), Treatment C (DTG/RPV 50 mg/25 mg: Product Code AM) and Treatment D (DTG/RPV 50 mg/25 mg: Product Code AQ) in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. All treatments will be administered in fed state. |
| Part 1 Cohort 1- Sequence 5 | EXPERIMENTAL | Each subject will receive a single dose of Treatment C (DTG/RPV 50 mg/25 mg: Product Code AM), Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet), and Treatment E (DTG/RPV 50 mg/25 mg: Product Code AK) in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. All treatments will be administered in fed state. |
| Part 1 Cohort 1- Sequence 6 | EXPERIMENTAL | Each subject will receive a single dose of Treatment E (DTG/RPV 50 mg/25 mg: Product Code AK), Treatment D (DTG/RPV 50 mg/25 mg: Product Code AQ) and Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet), in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. All treatments will be administered in fed state. |
| Part 2 Cohort 2- Sequence 1 | EXPERIMENTAL | Each subject will receive a single dose of Treatment F (DTG/RPV FDC-1) in fasted state, Treatment F (DTG/RPV FDC-1) in fed state and Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet) in fasted state in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. |
| Part 2 Cohort 2- Sequence 2 | EXPERIMENTAL | Each subject will receive a single dose of Treatment F (DTG/RPV FDC-1) in fed state, Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet) in fasted state and Treatment F (DTG/RPV FDC-1) in fasted state in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. |
| Part 2 Cohort 2- Sequence 3 | EXPERIMENTAL | Each subject will receive a single dose of Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet) in fasted state, Treatment F (DTG/RPV FDC-1) in fasted state and Treatment F (DTG/RPV FDC-1) in fed state in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. |
| Part 2 Cohort 3- Sequence 4 | EXPERIMENTAL | Each subject will receive a single dose of Treatment G (DTG/RPV FDC-2) in fasted state, Treatment G (DTG/RPV FDC-2) in fed state and Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet) in fasted state in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. |
| Part 2 Cohort 3- Sequence 5 | EXPERIMENTAL | Each subject will receive a single dose of Treatment G (DTG/RPV FDC-2) in fed state, Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet) in fasted state and Treatment G (DTG/RPV FDC-2) in fasted state in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. |
| Part 2 Cohort 3- Sequence 6 | EXPERIMENTAL | Each subject will receive a single dose of Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet) in fasted state and Treatment G (DTG/RPV FDC-2) fasted state and Treatment G (DTG/RPV FDC-2) in fed state in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. |
| Part 2 Cohort 4- Sequence 7 | EXPERIMENTAL | Each subject will receive a single dose of Treatment H (DTG/RPV FDC-3) in fasted state, Treatment H (DTG/RPV FDC-3) in fed state and Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet) in fasted state in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. |
| Part 2 Cohort 4- Sequence 8 | EXPERIMENTAL | Each subject will receive a single dose of Treatment H (DTG/RPV FDC-3) in fed state, Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet) in fasted state and Treatment H (DTG/RPV FDC-3) in fasted state in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. |
| Part 2 Cohort 4- Sequence 9 | EXPERIMENTAL | Each subject will receive a single dose of Treatment A (DTG 50 mg tablet plus RPV 25 mg tablet) in fasted state and Treatment H (DTG/RPV FDC-3) fasted state and Treatment H (DTG/RPV FDC-3) in fed state in period 1, period 2 and period 3 respectively with a washout period of \>=9 days between doses of study medication. |
| Sequence 1 | EXPERIMENTAL | Participants will receive the study Treatment A for 5 days (DTG 50mg q24h) in Period 1 followed by a washout period (\>=7days) and Treatment B for 5 days (DCV 60mg q24h) in Period 2 and Treatment C (DCV 60mg q24h + DTG 50mg q24h) for 5 days in Period 3 |
| Sequence 2 | EXPERIMENTAL | Participants will receive the study Treatment B for 5 days (DCV 60mg q24h) in Period 1 followed by a washout period (\>=7days) and Treatment A for 5 days (DTG 50mg q24h) in Period 2 and Treatment C (DCV 60mg q24h + DTG 50mg q24h) for 5 days in Period 3 |
| DTG/CBZ | EXPERIMENTAL | All subjects will be assigned to a single-sequence of three treatment periods without washout. Subjects will receive DTG 50 mg once daily (OD) for 5 days (Period 1), followed by CBZ 100 mg twice daily (BID) for 3 days (days 1-3 of Period 2), CBZ 200 mg BID for 3 days (days 4-6 of Period 2), CBZ 300mg BID for 10 days (days 7-16 of Period 2), followed by DTG 50 mg OD in combination with CBZ 300mg BID for 5 days (Period 3). |
| Cohort 1 | EXPERIMENTAL | Subjects in this cohort will take part in 4 treatment periods with one of the following treatments in each period. Subjects will receive all four treatments (one per period) in a random order. Treatment A = single dose DTG 50 mg fasted. Treatment B = single dose DTG 50 mg + Calcium Carbonate 1200 mg fasted. Treatment C = single dose of DTG 50 mg + Calcium Carbonate 1200 mg fed. Treatment D = single dose DTG 50 mg 2 hours prior to single dose Calcium Carbonate 1200 mg fasted |
| Cohort 2 | EXPERIMENTAL | Subjects in this cohort will take part in 4 treatment periods with one of the following treatments in each period. Subjects will receive all four treatments (one per period) in a random order. Treatment A = single dose DTG 50 mg fasted. Treatment E = single dose DTG 50 mg + Ferrous Fumarate 324 mg fasted. Treatment F = single dose of DTG 50 mg + Ferrous Fumarate 324 mg fed. Treatment G = single dose DTG 50 mg 2 hours prior to single dose Ferrous Fumarate 324 mg fasted |
| Arm 1 | EXPERIMENTAL | 33 subjects will receive a single dose of each of a tablet formulation of dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg in Period 1followed by dolutegravir 50 mg plus EPZICOM (abacavir 600mg/lamivudine 300 mg) in Period 2. Approximately 6 of these subjects will return for a third period where they will receive a single dose of dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg after a high fat breakfast. There will be a screening visit within 30 days prior to first dose and a follow-up visit 7-14 days after the last dose. |
| Arm 2 | EXPERIMENTAL | 33 subjects will receive dolutegravir 50 mg plus EPZICOM (abacavir 600mg/lamivudine 300 mg) in Period 1 followed by a single dose of a tablet formulation of dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg in Period 2. Approximately 6 of these subjects will return for a third period where they will receive a single dose of dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg after a high fat breakfast. There will be a screening visit within 30 days prior to first dose and a follow-up visit 7-14 days after the last dose. |
| Period 1 | OTHER | Subjects will be on individualize stable dose of methdaone for 8 days. |
| Period 2 | OTHER | Subjects will be on individualize stable dose of methadone and open label doses of 50mg Dolutegravir (DTG) every 12 hours for 5 days. |
| Run-In Period | OTHER | Ortho-Cyclen for 21 days. Only for subjects who are not already taking Ortho-Cyclen prior to the study |
| Sequence AB | EXPERIMENTAL | Subjects will take Ortho-Cyclen once a day from Day 1-21 of their menstrual cycle. In addition they will take dolutegravir 50 mg twice a day from Days 1-10 and placebo twice a day from Day 12-21 |
| Sequence BA | EXPERIMENTAL | Subjects will take Ortho-Cyclen once a day from Day 1-21 of their menstrual cycle. In addition they will take placebo twice a day from Days 1-10 and dolutegravir 50 mg twice a day from Day 12-21 |
| Part 1 | EXPERIMENTAL | In Part 1, approximately 12 healthy subjects will receive DTG 50mg q24h for 5 days in Period 1. Subjects will then be administered DTG 50mg q24h in combination with prednisone 60mg for 5 days followed by a 5 day taper (60 mg Days 1-5, 50 mg Day 6, 40 mg Day 7, 30 mg Day 8, 20 mg Day 9 and 10 mg Day 10 - total duration of 10 days) in Period 2. There will be a screening visit 30 days before the first dose and a follow-up visit 7-14 days after the last dose of drug. |
| Part 2 | EXPERIMENTAL | If DTG Cτ is reduced by more than 50% in Part 1, Part 2 will be carried out where a second cohort of subjects will receive DTG 50mg q24h DTG for 5 days in Period 1 followed by DTG 50mg q24h in combination with prednisone 20mg for 5 days followed by a 5 day taper (20 mg Days 1-5, 10 mg Days 6 and 7, 5 mg Days 8-10 - total duration of 10 days) in Period 2. There will be a screening visit 30 days before the first dose and a follow-up visit 7-14 days after the last dose of drug. |
| Single Arm | EXPERIMENTAL | Subjects will be randomized in a three-way crossover design to receive a single dose of each of two different tablet formulations of dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg or dolutegravir 50 mg plus EPZICOM (abacavir 600mg/lamivudine 300 mg). There will be a screening visit within 30 days prior to first dose and a follow-up visit 7-14 days after the last dose. |
| Part 1 Cohort 1 | EXPERIMENTAL | 8 subjects with moderate hepatic impairment defined by a Child-Pugh score of 7 to 9 will receive a single oral dose of GSK1349572 50 mg in the morning followed by 72 hour serial PK sampling. There will be a screening visit within 30 days prior to the dose of study drug and a follow-up visit within 7-10 days after the study drug. |
| Part 1 Cohort 2 | EXPERIMENTAL | 8 healthy subjects matched by gender, age and BMI to the subjects in Cohort 1 will receive a single oral dose of GSK1349572 50 mg in the morning followed by 72 hour serial PK sampling. There will be a screening visit within 30 days prior to the dose of study drug and a follow-up visit within 7-10 days after the study drug. |
| Part 2 Cohort 3 | EXPERIMENTAL | 8 subjects with mild hepatic impairment defined by a Child-Pugh score of 5 to 6 will receive a single oral dose of GSK1349572 50 mg in the morning followed by 72 hour serial PK sampling. There will be a screening visit within 30 days prior to the dose of study drug and a follow-up visit within 7-10 days after the study drug. This cohort will only be done if the AUC from Cohort 1 is greater than or equal to 2 times the AUC from Cohort 2. |
| Part 2 Cohort 4 | EXPERIMENTAL | 8 healthy subjects matched by gender, age and BMI to the subjects in Cohort 3 will receive a single oral dose of GSK1349572 50 mg in the morning followed by 72 hour serial PK sampling. There will be a screening visit within 30 days prior to the dose of study drug and a follow-up visit within 7-10 days after the study drug. This cohort will only be done if the AUC from Cohort 1 is greater than or equal to 2 times the AUC from Cohort 2. |
| Part A | EXPERIMENTAL | Approximately 12 subjects will be enrolled. In the first treatment period, all subjects will receive GSK1349572 50 mg every 24 hours for 5 days. In Period 2, subjects will receive GSK1349572 50 mg every 24 hours in combination with fosamprenavir 700 mg plus ritonavir 100 mg every 12 hours for 10 days. Day 1 of Period 2 will be the day after Day 5 of Period 1. Subjects will have a screening visit within 30 days prior to the first dose of study drug, two treatment periods, and a follow-up visit 7-14 days after the last dose of study drug. |
| Part B | EXPERIMENTAL | Approximately 15 subjects will be enrolled and receive three single doses of GSK1349572 approximately one week apart. One will be the current tablet formulation containing micronized drug substance and 2 will be new tablet versions, one containing unmicronized drug substance and one containing an intermediate particle size drug substance. Subjects will have a screening visit within 30 days prior to the first dose of study drug, three treatment periods, and a follow-up visit 7-14 days after the last dose of study drug. |
| ARM 3 | EXPERIMENTAL | ARM 3: GSK1349572 50mg QD and TPV/RTV 500/200mg BID (Treatment C). |
| Name | Type | Description |
|---|---|---|
| Dolutegravir 50mg Tab | DRUG | Participants will receive Dolutegravir 50mg |
| Dolutegravir/Lamivudine 50 MG-300mg Oral Tablet [DOVATO] | DRUG | Participants will receive Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet \[DOVATO\] |
| Dolutegravir plus Tenofovir disoproxil fumarate (TDF)/ lamivudine (3TC) | DRUG | Participants will receive Dolutegravir plus Tenofovir disoproxil fumarate (TDF)/ lamivudine (3TC) |
| Dolutegravir | DRUG | Dolutegravir will be administered once daily. |
| Lamivudine | DRUG | Lamivudine will be administered once daily. |
| Bictegravir | DRUG | Bictegravir will be administered once daily. |
| Emtricitabine | DRUG | Emtricitabine will be administered once daily. |
| Tenofovir alafenamide | DRUG | Tenofovir alafenamide will be administered once daily. |
| DTG/3TC | DRUG | DTG/3TC FDC was administered once daily. |
| Cabotegravir (CAB) LA | DRUG | CAB LA will be administered as a gluteal intramuscular injection once every 2 months in combination with RPV LA. |
| Rilpivirine (RPV) LA | DRUG | RPV LA will be administered as a gluteal intramuscular injection once every 2 months in combination with CAB LA. |
| DTG/3TC FDC | DRUG | DTG/3TC FDC will be available as white, oval, film-coated tablets at a unit dose strength of 50 mg/300 mg. Participants will take DTG/3TC once daily via oral route. |
| CAR | DRUG | Participants who are randomized to the CAR arm will continue to take the current treatment until Week 52. CAR will include 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted. |
| Dolutegravir + Lamivudine FDC | DRUG | Dolutegravir + Lamivudine FDC is available as white oval film-coated tablets which are packed in high density polyethylene (HDPE) bottles with induction seals and child-resistant closures. Each 60 milliliter (mL) bottle contains 30 tablets |
| DTG + 3TC FDC | DRUG | DTG + 3TC FDC was available as a 50/300 mg tablet to be given orally once daily. |
| DTG + 3TC | DRUG | DTG+3TC is supplied as white, oval, film-coated, fixed dose combination tablet. The tablets will be available in packed high density polyethylene (HDPE) bottles with induction seals and child-resistant closures. |
| TAF based regimen (TBR) | DRUG | Participants will continue to receive their TBR. |
| Dolutegravir (DTG) | DRUG | DTG is available as 50 mg white, round, biconvex, film coated tablet debossed on one side with 'SV 572' and on the other side with '50'. The tablets are packaged into high density polyethylene (HDPE) bottles with induction seals and child resistant closures. Each 45 ml bottle contains 30 tablets and a desiccant. DTG 50 mg tablet will be orally administered once daily with or without food upto 148 weeks. |
| Lamivudine (3TC) | DRUG | Lamivudine is available as swedish orange, 'AA' sized elongated double blind HPMC capsules containing 300 mg lamivudine to visually match overencapsulated TDF/FTC FDC tablet. The capsules are packaged into HDPE bottles with induction seals and child resistant closures. Each 150 mL bottle contains 30 capsules and a desiccant. Overencapsulated 3TC 300 mg tablet will be orally administered once daily with or without food upto 96 weeks. From Week 96 to Week 148, lamivudine will be dispensed as 300 mg white, diamond shaped, scored, film coated tablets debossed with 'GX CJ7' on both sides, packed in over labelled HDPE bottles with child-resistant closures each containing 30 tablets. |
| Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC FDC) | DRUG | Tenofovir disoproxil fumarate and Emtricitabine are available as swedish orange, 'AA' sized elongated double blind HPMC capsules containing 300 mg TDF and 200 mg FTC to visually match overencapsulated 3TC tablet. The capsules are packaged into HDPE bottles with induction seals and child resistant closures. Each 150 mL bottle contains 30 capsules and a desiccant. Overencapsulated tenofovir disoproxil fumarate/emtricitabine tablet will be orally administered once daily with or without food upto 96 weeks. From Week 96 to Week 148, tenofovir disoproxil fumarate/emtricitabine will be dispensed as 300/200 mg white, blue, capsule shaped, film coated tablets debossed with 'GILEAD' on one side and '701' on another side, packed in overlabelled HDPE bottles with polypropylene childresistant closures each containing 30 tablets and a desiccant. |
| DTG 50 mg | DRUG | Participants received one oral tablet of 50 mg DTG daily administered concomitantly with RPV. Each DTG tablet contained 52.62 mg dolutegravir sodium salt, which was equivalent to 50 mg dolutegravir free acid. |
| RPV 25 mg | DRUG | Participants received DTG 50 milligrams (mg) + RPV 25 mg together once daily at approximately the same time, with a meal, in an open-label fashion up to Week 52 during early switch phase. Participants continued to receive DTG 50 mg + RPV 25 mg up to Week 148 during the Late Switch Phase. Participants who successfully completed 148 weeks of treatment were given the opportunity to continue to receive DTG + RPV once daily in the Continuation Phase (after Week 148), one oral tablet of 25 mg RPV daily administered concomitantly with DTG along with a meal. Each RPV tablet contained 27.5 mg of rilpivirine hydrochloride, which was equivalent to 25 mg of RPV. |
| EFV 600 mg | DRUG | EFV is supplied as film-coated capsule-shaped oral tablet containing 600 mg of EFV and must be administered without food |
| DTG 50 mg /ABC 600 mg /3TC 300 mg FDC tablets | DRUG | The DTG 50 mg /ABC 600 mg /3TC 300 mg FDC tablet is a purple, oval, biconvex tablets. The tablet contains 52.6 mg DTG sodium which is equivalent to 50 mg DTG free acid, 702 mg ABC sulphate which is equivalent to 600 mg ABC and 300 mg 3TC. |
| DTG | DRUG | DTG is supplied as 50 mg tablets |
| LPV/RTV | DRUG | LPV/RTV is supplied as the LPV/RTV oral tablet, which contains 200 mg of LPV and 50 mg of RTV |
| Two NRTIs | DRUG | Investigators will choose a dual NRTI background regimen for each subject . In consultation with the medical monitor, 3TC may be added as a third NRTI to a dual-NRTI background regimen in subjects with chronic HBV infection and evidence of HIV resistance to 3TC |
| Dolutegravir/abacavir/lamivudine FDC | DRUG | Dolutegravir/abacavir/lamivudine FDC tablets, 50 mg/600 mg/300 mg |
| Atazanavir | DRUG | Atazanavir capsule 300 mg |
| Ritonavir | DRUG | Ritonavir tablet 100 mg |
| Tenofovir/emtricitabine FDC | DRUG | Tenofovir/emtricitabine FDC tablet 300 mg/200 mg of FTC |
| Atripla | DRUG | Atripla once daily on an empty stomach |
| Abacavir/Lamivudine | DRUG | taken once daily; also known as EPZICOM |
| Abacavir/Lamivudine Placebo | DRUG | matching placebo taken once daily |
| Dolutegravir placebo | DRUG | matching placebo taken once daily |
| Atripla placebo | DRUG | matching placebo taken once daily on an empty stomach |
| GSK1349572 | DRUG | 50mg once daily |
| Raltegravir | DRUG | 400mg twice daily |
| GSK1349572 Placebo | DRUG | Inactive placebo tablet once daily |
| Raltegravir Placebo | DRUG | Inactive placebo tablet twice daily |
| GSK1349572 (dolutegravir) | DRUG | GSK1349572 50 mg taken once daily with or without food |
| ABC/3TC | OTHER | Abacavir/Lamivudine background therapy once daily |
| TDF/FTC | OTHER | Tenofovir/emtricitabine background therapy once daily |
| Dolutegravir 50 MG / Lamivudine 300 MG Oral Tablet [Dovato] | DRUG | change of current antiretroviral treatment to DTG 50 mg/3TC 300 mg QD |
| GSK1349572 (Cohort I) | DRUG | 50 mg once daily |
| GSK1349572 (Cohort II) | DRUG | 50 mg twice daily |
| efavirenz | DRUG | approved therapy for HIV-1 infection, used as an internal study control |
| Placebo | DRUG | Placebo is a tablet with no drug in it. |
| Dolutegravir/Rilpivirine FDC | DRUG | Dolutegravir/Rilpivirine will be administered. |
| Dolutegravir + Lamivudine FDC Formulation 1 | DRUG | Single dose of DTG 50 mg combined with 3TC 300 mg in a FDC formulation 1 tablet will be administered to randomized subjects in treatment periods 1 and 2 (under fasted state) of Part 1 and the first 16 subjects in treatment period 3 (under fed) of Part 1 with 240 mL of room temperature water. \<br\>FDC formulation 1 tablets will be oval, biconvex, white, film coated tablet engraved 'SV H7I' on one face. |
| Dolutegravir + Lamivudine FDC Formulation 2 | DRUG | Single dose of DTG 50 mg combined with 3TC 300 mg in a FDC formulation 2 tablet will be administered to randomized subjects in treatment periods 1 and 2 (under fasted state) and the first 16 subjects in treatment period 3 (under fed) of Part 2 with 240 mL of room temperature water. \<br\>FDC formulation 2 tablets will be oval, biconvex, white, film coated tablet engraved 'SV 13N' on one face. |
| DTG/ABC/3TC FDC DISPERSIBLE TABLET | DRUG | DTG/ABC/3TC FDC dispersible tablet |
| EPZICOM (ABC/3TC) | DRUG | EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with "GS FC2" on one side. |
| TIVICAY (DTG) | DRUG | TIVICAY will be available as white, round, biconvex tablets |
| RPV | DRUG | RPV is provided as a white to off-white, film-coated, round, biconvex tablet containing RPV 25 mg, debossed with TMC on one side and 25 on the other side. Subjects will receive a single oral dose of RPV 25 mg tablet with 240 mL of water. |
| DTG/RPV FDC | DRUG | DTG/RPV FDC is provided as a pink, film coated, oval biconvex tablet containing FDC of DTG 50 mg and RPV 25 mg, debossed with SV J3T on one face. Subjects will receive a single oral dose of DTG/RPV 50 mg/25 mg FDC tablet with 240 mL of water. |
| Dolutegravir 50 mg tablet | DRUG | A white, film-coated, round tablet debossed with SV 572 on one side and 50 on the other side. Single dose of one tablet will be administered with 240 mL of water. |
| Lamivudine 300 mg tablet | DRUG | Gray, diamond-shaped tablet, engraved "GX EJ7" on one side and plain on the other side. Single dose of one tablet will be administered with 240 mL of water. |
| Dolutegravir/Lamivudine 50 mg/300 mg Tablet (Product Code AA) | DRUG | Immediate release oval tablet embossed 'gsk' on one face with white film coat. Single dose of one tablet will be administered with 240 mL of water. |
| Dolutegravir/Lamivudine 50 mg/300 mg Tablet (Product Code AB) | DRUG | Immediate release oval tablet embossed 'gsk' on one face with white film coat. Single dose of one tablet will be administered with 240 mL of water. |
| BMS955176 | DRUG | BMS955176 |
| DTG/RPV 50 mg/25 mg: Product Code AS | DRUG | DTG/RPV will be supplied as a pink, film coated, round biconvex tablet with a unit dose strength of 50 mg DTG and 25 mg RPV to be administered orally |
| DTG/RPV 50 mg/25 mg: Product Code AM | DRUG | DTG/RPV will be supplied as a pink, film coated, oval, biconvex tablet with a unit dose strength of 50 mg DTG and 25 mg RPV to be administered orally |
| DTG/RPV 50 mg/25 mg: Product Code AQ | DRUG | DTG/RPV will be supplied as a pink, film coated, round, biconvex tablet with a unit dose strength of 50 mg DTG and 25 mg RPV to be administered orally |
| DTG/RPV 50 mg/25 mg: Product Code AK | DRUG | DTG/RPV will be supplied as pink, film coated, oval, biconvex tablet with a unit dose strength of 50 mg DTG and 25 mg RPV to be administered orally |
| DTG/RPV 50 mg/25 mg: Product Code AR | DRUG | DTG/RPV will be supplied as a pink, film coated, round, biconvex tablet with a unit dose strength of 50 mg DTG and 25 mg RPV to be administered orally |
| DCV | DRUG | DCV is provided as a plain, green, biconvex, pentagonal film-coated tablet |
| CBZ | DRUG | CBZ will be supplied as 100 mg and 200 mg extended release tablet to be administered orally |
| Dolutegravir 50 mg | DRUG | One tablet ( 50 mg) will be administered orally as a single dose in each period per the random code |
| Calcium Carbonate 1200 mg | DRUG | Two tablets (2 X 600 mg) will be administered orally as a single dose in three out of four periods to Cohort 1 only per the random code. Calcium carbonate will be given in fasted state, fed state and 2 hours before dolutegravir administration. |
| Ferrous Fumarate 324 mg | DRUG | One tablet (324 mg) will be administered orally as a single dose in three out of four periods to Cohort 2 only per the random code. Ferrous fumarate will be given in fasted state, fed state and 2 hours before dolutegravir administration. |
| Dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg | DRUG | Dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg is an experimental fixed dose combination tablet of an experimental integrase inhibitor (dolutegravir) and two FDA approved nucleoside reverse transcriptase inhibitors (abacavir and lamivudine) |
| abacavir 600 mg/lamivudine 300 mg | DRUG | This is an FDA approved fixed dose combination tablet of two nucleoside reverse transcriptase inhibitors |
| BCV | DRUG | 800 mg q8h |
| TVR | DRUG | 750 mg q8h |
| Methadone | DRUG | Methadone is a synthetic opioid used in the treatment of opioid dependence. Subjects will be on individualize stabe dose for 8 days. |
| Ortho-Cyclen | DRUG | Ortho-cyclen is an oral contraceptive. |
| Rlipivirine | DRUG | 25mg q24h |
| GSK1265744 | DRUG | 30mg q24h |
| Prednisone | DRUG | Prednisone is a commonly used corticosteroid used for a variety of medical condiitons |
| Dolutegravir 50 mg oral granules | DRUG | Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV. |
| Rifampin | DRUG | Rifampin is approved by the FDA for the treatment of tuberculosis. |
| Rifabutin | DRUG | Rifabutin is approved by the FDA for the treatment of tuberculosis. |
| Iohexol Injection | DRUG | Iohexol is an FDA approved radiologic contrast medium |
| Para-aminohippurate infusion | DRUG | Para-aminohippurate is an agent to measure effective renal plasma flow. |
| Fosamprenavir | DRUG | Fosamprenavir is a drug in the protease inhibitor class that is approved by the FDA for the treatment of HIV infection. |
Inclusion Criteria: * Documentation of HIV-1 status: HIV-1 infection, documented by any licensed rapid HIV test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to entry and confirmed by a licensed Western blot or a second antibody test by a method other than the ...
GSK1349572 is an investigational small molecule developed by GSK plc (ticker: GSK) for the treatment of human immunodeficiency virus (HIV) infection. It has been studied in Phase 3 clinical trials, including in patients with HIV and co-infections such as herpesviridae and tuberculosis. It is also known as dolutegravir.
GSK1349572 is being developed for the treatment of HIV infection, including HIV-1, and for HIV in patients with co-infections such as herpesviridae and tuberculosis. It is an investigational therapy and has been evaluated in Phase 3 trials in antiretroviral-experienced adults.
GSK1349572 is developed by GSK plc, which trades under the ticker GSK. The company has sponsored clinical trials of the drug in HIV infection and related co-infections.
GSK1349572 is in Phase 3 clinical development. It has completed nine clinical trials, including a Phase 3 study, and is not yet approved. The Phase 3 trial NCT01231516 compared GSK1349572 with raltegravir in antiretroviral-experienced, integrase inhibitor-naive adults.
GSK1349572 has been studied in nine completed clinical trials, including Phase 1 and Phase 3 studies. Key trials include NCT01332565 in healthy Japanese subjects, NCT01231542 evaluating drug interactions with rifampin and rifabutin, NCT01231529 in hepatic impairment, and the Phase 3 trial NCT01231516 in HIV-infected adults.
Yes, GSK1349572 is also known as dolutegravir. Other alternative names include GSK1349572 and MaaloxAdvanced Maximum Strength, GSK1349572 250 mg, GSK1349572 and tenofovir, and GSK1349572 (Cohort I). It is a small molecule developed by GSK plc for HIV infection.