Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Dolutegravir · 16 trials · 6 indications
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 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.
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.
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.
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)
Steady state total and R-methadone PK measure: AUC (0-t), Cmax and Ct.
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
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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. |
| 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 | EXPERIMENTAL | dolutegravir plus background antiretroviral therapy optimised at Day 8 |
| 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 |
| 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. |
| 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. |
| Treatment A | EXPERIMENTAL | Single DTG tablet under fed conditions for a specified period |
| Treatment B | EXPERIMENTAL | Two BMS955176 tablets under fed conditions for a specified period |
| Treatment C | EXPERIMENTAL | Single DTG tablet and Two BMS955176 tablets under fed conditions for a specified period |
| 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 |
| 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. |
| 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 have a screening visit within 30 days prior to the first dose of study drug, five treatment periods containing a single dose of study drug, followed by 48 hours of serial PK collection. In the 5 treatment periods subjects will receive DTG granule formulation 1) directly to mouth; 2) with purified water; 3) with Contrex brand water; and 4) with milk-based infant formula. They will also receive the current 50 mg tablet formulation administered with tap water. These treatments will be administered in a random order. Subjects will check out of the unit on Day 3 after the 48 hour PK sample in each period. Study periods will be separated by at least 5 days. Subjects will have a follow-up visit 5-7 days after last dose of DTG given. |
| Name | Type | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| 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. |
| 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 |
| 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. |
| Methadone | DRUG | Methadone is a synthetic opioid used in the treatment of opioid dependence. Subjects will be on individualize stabe dose for 8 days. |
| 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. |
Inclusion Criteria: * Participants with age \>=18 years (or older, if required by local regulations) at the time of obtaining informed consent. * An individual participant is eligible to participate if they are not pregnant (as confirmed by a negative serum human chorionic gonadotropin (hCG) test a...
Dolutegravir is an investigational small molecule being developed for the treatment of HIV infections, including Human Immunodeficiency Virus I, HIV Infections, and co-infections with Hepatitis and Herpesviridae. It is currently in Phase 3 clinical development.
Dolutegravir is being developed by GSK plc, which trades under the ticker GSK. The company is conducting clinical trials to evaluate the drug's safety and efficacy in treating HIV infections.
Dolutegravir is in Phase 3 clinical development. It is an investigational drug and has not yet been approved by regulatory authorities. Clinical trials are ongoing to assess its effectiveness in treating HIV infections.
Dolutegravir has been studied in multiple clinical trials, including NCT01353716, NCT01425099, NCT01762995, and NCT02738931. These trials have investigated its pharmacokinetics, drug interactions, and bioavailability in healthy volunteers and individuals with HIV.
Dolutegravir is also known as Dolutegravir/Rilpivirine FDC, Dolutegravir/Rilpivirine, Dolutegravir/Lamivudine (DTG/3TC), and Dolutegravir/Lamivudine. These names refer to fixed-dose combinations that include dolutegravir as a component.
Dolutegravir is a small molecule that targets HIV integrase, an enzyme essential for viral replication. By inhibiting this enzyme, it prevents the virus from integrating its genetic material into host cells, thereby reducing viral load in infected individuals.