Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK1278863 · 16 trials · 5 indications
Blood samples were collected from participants for measurement of Hgb values. The Baseline value was the latest pre-dose assessment. Change from Baseline at Week 4 was calculated by subtracting Baseline value from the post-dose visit value. The analysis was performed on All Treated Subjects Population which comprised of all participants who received at least one dose of GSK1278863.
Blood samples were collected from participants for measurement of Hgb values. The Baseline value was the latest pre-dose assessment. Change from Baseline at Week 4 was calculated by subtracting Baseline value from the post-dose visit value. The change in Hgb at Week 4 was classified into different categories (i.e., \<=-2.0, \>-2.0 to -1.0, \>-1.0 to 0, \>0 to 1.0, \>1.0 to 2.0, and \>2 g/dL), and the number of participants in each category were summarized.
Blood samples were collected from participants for measurement of Hgb values. Baseline is the average of Hgb measured at Week -2 and Day 1 visits. Change from Baseline at Day 29 was defined as post dose value at Day 29 minus Baseline value. The analysis was performed on intent-to-treat (ITT) Population which comprised of all randomized participants who received at least one dose of study treatment, had a Baseline and at least one corresponding on treatment assessment, including Hgb.
Baseline was defined as the value on Day 1. CFB was calculated by subtracting the baseline value from the post-dose value at Week 4. To model the dose-response relationship a four-parameter Emax model was used. E0 is the expected Hgb change from Baseline for a participant receiving placebo and experiencing the average Hgb Baseline observed in the study. Emax is the expected Hgb change from Baseline for a participant receiving the highest dose above which no further increase in response can be achieved. ED50 is the dose that attains the intermediate response. Gamma is the slope parameter. Minimal Effective Dose (MED) is defined as the smallest dose that achieves a placebo-corrected change of 0.5 g/dL over Week 4. Target dose (TD) is defined as the dose that achieves a placebo-corrected 1.0 g/dL change over Week 4. Maximum Acceptable Dose (MAD) is defined as the dose that achieves a placebo-corrected 2.0 g/dL change over Week 4.
Baseline Hgb value was the average of three Hgb values taken during screening period at Week (W) -4, W-2 and Day 1. Change from Baseline in Hgb was calculated as W4 value minus the Baseline value. To model the dose-response relationship a four-parameter Emax model was used. The dose response dataset was based on all non-missing data collected up to W4. Participants (par.) who had a Week 2 Hgb measurement, but a missing Week 4 Hgb measurement were included with a change from Baseline at Week 4 value imputed as twice the change from Baseline at Week 2. E0 is the expected Hgb change from Baseline for a par. receiving placebo and experiencing the average Hgb Baseline observed in the study. Emax is the expected Hgb change from Baseline for a par. receiving the highest dose above which no further increase in response can be achieved. ED50 is the dose that attains the intermediate response. Gamma is the slope parameter. Alpha is the coefficient of the model covariate for centred Baseline.
S100 beta is a CSF biomarker that rise significantly in participants with neurologic injury following DTA/TAAA surgery. CSF samples were collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF S100 beta. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline value minus Baseline value.
GFAP is a CSF biomarker that rise significantly in participants with neurologic injury following DTA/TAAA surgery. CSF samples for the analysis of GFAP was collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF GFAP. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline value minus Baseline value.
The original Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-10.0 g/dL (8.0-10.0 g/dL USA site only) and for Group 2- rhEPO users with a stable baseline Hgb of 9.0-10.5 g/dL (9.0-10.5 g/dL USA site only); the Hgb target range was 9.0 to 10.5 g/dL (9.0-10.5 g/dL USA site only). The study amended Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-11.0 g/dL and Group 2- rhEPO users with a stable baseline Hgb of 9.0-11.5 g/dL; Hgb target range - 10.0 to 11.5 g/dL. Data are presented for those participants following the original criteria ("Original") and those following the amended ("Amended") criteria. The primary objective was to characterize the ability of GSK1278863 to achieve mean Hgb response within the target range.
Modeled Hgb change from Baseline over 4 weeks of treatment. Change from Baseline is the actual value of Hgb at Week 4 minus the Baseline value. For modeled change at Week 4 participants required a Baseline and two or more non missing post-baseline values. Baseline is the average of Week -2, -1 and Day 1 values. The model included fixed effects for Baseline Hgb, treatment, and treatment by day interaction. Covariate analysis for modeled Hgb change was performed. Random effects were fitted in the intercept and the slope over time.
Modeled Hgb change from baseline over 4 weeks was derived using a random coefficient mixed effects linear regression model. The model included fixed effects for baseline Hgb, treatment and a treatment by day interaction. Random effects was fitted in the intercept and the slope over time. All data up until investigational product discontinuation was included for Hgb efficacy evaluable participants; where efficacy evaluable was defined as having a baseline and at least 2 on-treatment Hgb assessments. Baseline was the average of Week -2 , Week -1 and Day 1 visits. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values.
AE is 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. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is 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, or is a congenital anomaly/birth defect or is medically significant.
Twelve lead ECGs were recorded with the participant lying supine, having rested in this position for at least 5 minutes before each recording. Full 12 lead ECGs were recorded using an ECG device that automatically calculated the heart rate and measured PR, QRS, RR, QT and QT, QT corrected by Bazett's formula (QTcB) and QT corrected by Fridericia's formula (QTcF) intervals. Number of participants with abnormal (not clinically significant \[NCS\] and clinically significant \[CS\]) ECG findings are presented.
Vital signs included heart rate, systolic and diastolic blood pressure and were performed with the participant in a supine position after the participant had rested for at least 5 minutes. Number of participants with vital signs of potential clinical importance are presented.
Clinical chemistry analyte of potential clinical concern included albumin, calcium, creatinine, glucose, magnesium, phosphorus, potassium, sodium and bicarbonate. Number of participants with clinical chemistry abnormalities of potential clinical importance are presented.
Hematology parameters included platelet count, red blood cell (RBC) count, white blood cell WBC count (absolute), hemoglobin, hematocrit, Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils and basophils. Number of participants with clinical hematology abnormalities of potential clinical importance are presented.
The effect of an oral dose of GSK1278863 on the pharmacokinetics of pioglitazone will be assessed using the following PK parameters: maximum observed concentration (Cmax), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC (0-infinity)
The effect of an oral dose of GSK1278863 on the pharmacokinetics of rosuvastatin will be assessed using the following PK parameters: Cmax and AUC (0-infinity)
The effect of trimethoprim on the pharmacokinetics of GSK1278863 and six predominant metabolites (GSK2391220 \[M2\], GSK2506104 \[M3\], GSK2487818 \[M4\], GSK2506102 \[M5\], GSK2531398 \[M6\], GSK2531401 \[M13\]) will be assessed using the following PK parameters: Cmax and AUC (0-infinity)
Muscle strength is a measure of the amount of force produced during a maximal voluntary contraction of the elbow flexors. It will be assessed in the non-dominant arm by a maximal isometric (fixed length) contraction using Cybex ergometer in a seated position after completion of eccentric exercise
Plasma concentrations of GSK1278863 and its metabolites (GSK2391220 \[M2\], GSK2506104 \[M3\], GSK2487818 \[M4\], GSK2506102 \[M5\], GSK2531398 \[M6\], and GSK2531401 \[M13\]) and derived pharmacokinetic parameters including maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax), Area under the concentration-time curve (AUC)
Change from baseline in QTcF interval at each time-point (average of at least three 12-lead Holter ECG replicates per time-point (Pre-dose, Day 1 \[0.25h, 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 18h\] and 24h) for 75 and 500 mg dose of GSK1278863 as compared with time-matched placebo
12-lead ECGs will be obtained at each time-point
Vital Signs includes. temperature, systolic and diastolic blood pressure (BP) and pulse
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Clinical Laboratory Tests includes Hematology, Clinical Chemistry and Urinalysis
Serial blood samples were collected from participants at indicated time points for Pharmacokinetic (PK) analysis of GSK1278863 and its metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401). Geometric mean and geometric coefficient of variation has been presented for all metabolites. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants. PK Population comprised of participants in the 'All Subjects' Population for whom a PK sample was obtained and analyzed.
Serial blood samples were collected from participants at indicated time points for PK analysis of GSK1278863 and its metabolites (GSK2487818 and GSK2531398). Geometric mean and geometric coefficient of variation has been presented for all metabolites. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants.
Serial blood samples were collected from participants at indicated time points for PK analysis of GSK1278863 and its metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401). Geometric mean and geometric coefficient of variation has been presented for all metabolites. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is 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; other important medical events; or is associated with liver injury and impaired liver function.
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is 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; other important medical events; or is associated with liver injury and impaired liver function.
ECG measurements were taken with the participants in supine position for at least 5 minutes. The number of participants with clinically significant abnormal ECG measurement following single dose administration for worst case post-Baseline visit has been presented.
ECG measurements were taken with the participants in supine position for at least 5 minutes. The number of participants with clinically significant abnormal ECG measurement following single dose administration for worst case post-Baseline visit has been presented.
Vital sign measurements included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Vital signs were measured after the participants rested in a supine or semi-supine position for 5 minutes prior to the procedure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter.
Vital sign measurements included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Vital signs were measured after the participants rested in a supine or semi-supine position for 5 minutes prior to the procedure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter.
A brief physical assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen) were planned to be performed by qualified licensed, medical professional (i.e., physician, physician assistant, or nurse practitioner) but was not performed.Since data was not collected, no analysis was performed.
A brief physical assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen) were planned to be performed by qualified licensed, medical professional (i.e., physician, physician assistant, or nurse practitioner) but was not performed. Since data was not collected, no analysis was performed.
Hematology parameters assessed were: platelet count, red blood cell count, white blood cell count, hemoglobin, reticulocyte count, hematocrit, absolute neutrophil count (ANC), monocytes, lymphocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. When a high or low value was reported, all values are presented for that time point and parameter.
Hematology parameters assessed were: platelet count, red blood cell count, white blood cell count, hemoglobin, reticulocyte count, hematocrit, neutrophils, monocytes, lymphocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. When a high or low value was reported, all values are presented for that time point and parameter.
Chemistry parameters assessed were: Blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, creatine phosphokinase (CPK), potassium, chloride, total carbon dioxide (CO2), calcium, glycosylated hemoglobin (HbA1C), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma glutamyltransferase (GGT), Alkaline phosphatase (ALP), High sensitivity C-reactive protein (hsCRP), total and direct bilirubin, uric acid, albumin and total protein. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter.
Chemistry parameters assessed were: Blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, creatine phosphokinase (CPK), potassium, chloride, total carbon dioxide (CO2), calcium, glycosylated hemoglobin (HbA1C), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma glutamyltransferase (GGT), Alkaline phosphatase (ALP), High sensitivity C-reactive protein (hsCRP), total and direct bilirubin, uric acid, albumin and total protein. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). When a high or low value was reported, all values are presented for that time point and parameter.
The pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Cmax could not be determined as data was below the limit of quantification.
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Cmax could not be determined as data was below the limit of quantification.
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tmax could not be determined as data was below the limit of quantification.
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tmax could not be determined as data was below the limit of quantification.
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. t1/2 could not be determined as data was below the limit of quantification.
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. t1/2 could not be determined as data was below the limit of quantification.
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tlag could not be determined as data was below the limit of quantification.
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. Tlag could not be determined as data was below the limit of quantification.
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-inf) could not be determined as data was below the limit of quantification.
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-inf) could not be determined as data was below the limit of quantification.
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-t) could not be determined as data was below the limit of quantification.
The pharmacokinetic parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Version 5.2 or higher. All calculations of non-compartmental parameters were based on actual sampling times. AUC (0-t) could not be determined as data was below the limit of quantification.
1\. To assess the relative bioavailability GSK1278863A following single-dose administration under fasting and fed (standard high fat/calorie meal) conditions
| Arm | Type | Description |
|---|---|---|
| GSK1278863 | EXPERIMENTAL | Subjects will receive GSK1278863 once daily orally at a starting dose of 4 milligrams (mg) on Day 1, and continued until the day of Week 4. From Weeks 4 to 24, interruption of treatment or dose adjustments will be made within the maintenance dose range of 1 mg to 24 mg according to the dose adjustment algorithm to achieve and/or maintain Hgb within the target range (10.0 to 12.0 g/dL) based on the Hgb value measured every 4 weeks. Dose changes will be made every 4 weeks. Iron replacement therapy will be given according to the standard starting criteria. |
| GSK1278863 10 mg | EXPERIMENTAL | Subject will receive 10 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days). |
| GSK1278863 15 mg | EXPERIMENTAL | Subject will receive 15 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days). |
| GSK1278863 25 mg | EXPERIMENTAL | Subject will receive 25 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days). |
| GSK1278863 30 mg | EXPERIMENTAL | Subject will receive 30 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days). |
| Placebo | PLACEBO_COMPARATOR | Subject will receive GSK1278863 matching placebo three-times weekly for 4 weeks (up to 29 days). |
| GSK1278863 4 milligrams (mg) | EXPERIMENTAL | Subjects will receive GSK1278863 4 mg once daily for 4 weeks |
| GSK1278863 6 mg | EXPERIMENTAL | Subjects will receive GSK1278863 6 mg once daily for 4 weeks |
| GSK1278863 8 mg | EXPERIMENTAL | Subjects will receive GSK1278863 8 mg once daily for 4 weeks |
| GSK1278863 4 mg | EXPERIMENTAL | Subjects will take GSK1278863 4 mg blinded once daily (OD) orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. |
| GSK1278863 12 mg | EXPERIMENTAL | Subjects will take GSK1278863 12 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. |
| Control | ACTIVE_COMPARATOR | Subjects will take GSK1278863 matching placebo blinded OD orally for 4 weeks with a glass of water. From Week 4, rhEPO will be administered and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. |
| 0.5 mg GSK1278863 | EXPERIMENTAL | once daily |
| 2 mg GSK1278863 | EXPERIMENTAL | once daily |
| 5 mg GSK1278863 | EXPERIMENTAL | once daily |
| rhEPO | ACTIVE_COMPARATOR | as required |
| 0.5mg GSK1278863 | EXPERIMENTAL | Once daily |
| 2mg GSK1278863 | EXPERIMENTAL | Once daily |
| 5mg GSK1278863 | EXPERIMENTAL | Once daily |
| Part A: GSK1278863, pioglitazone and rosuvastatin | EXPERIMENTAL | Subjects will receive single, oral 15 milligram (mg) pioglitazone, 10 mg rosuvastatin and 25 mg dose of GSK1278863 (Treatment A) or 15 mg pioglitazone and 10 mg rosuvastatin (Treatment B) on Day 1 and a 25 mg dose of GSK1278863 alone on Day 2 in two treatment periods as per treatment sequence AB or BA. The 2 treatment periods will be separated by a wash out period of approximately 7 days |
| Part B: GSK1278863 and trimethoprim | EXPERIMENTAL | Subjects will receive a single, oral 25 mg dose of GSK1278863 on Day 1 and Day 6 morning. The subjects will also receive 200 mg dose of trimethoprim twice daily from Day 3 to 6, with Day 6 dosing being concomitant with morning dosing of GSK1278863 |
| GSK1278863 (Part A) | EXPERIMENTAL | All subjects will receive a single, oral 500 mg dose of GSK1278863 on Day 1 administered as 5 x 100 mg tablets of GSK1278863. Additional doses/cohorts may be added depending upon the emerging safety, tolerability, pharmacokinetic and/or pharmacodynamics findings at the 500 mg dose level in Part A |
| GSK1278863 (75 mg/500 mg)/Moxifloxacin 400 mg/Placebo (Part B) | EXPERIMENTAL | Subjects will be assigned to one of four treatment sequences (A-1 x Moxifloxacin placebo tablet, 3 x 25 mg tablets of GSK1278863, 2 x GSK1278863 matched placebo; B-1 x Moxifloxacin placebo tablet, 5 x 100 mg tablets of GSK1278863; C-1 x Moxifloxacin placebo tablet, 5 x GSK1278863 matched placebo tablets; D-1 x 400 mg Moxifloxacin tablet, 5 x GSK1278863 matched placebo tablets) (ABDC, BCAD, CDBA, DACB) in accordance with the randomization schedule |
| Cohort 1 | EXPERIMENTAL | Subjects on continuous ambulatory peritoneal dialysis (CAPD) will receive 5 mg of GSK1278863 orally, once daily for 14 days. |
| Cohort 2 | EXPERIMENTAL | Subjects on automated peritoneal dialysis (APD) will receive 5 mg of GSK1278863 orally, once daily for 14 days |
| Cohort 1 Part A | EXPERIMENTAL | Healthy subjects in this arm will receive single applications of GSK1278863 or placebo (with 6:2 ratio) on intact skin in two escalating dosing periods each separated by 10 days. The first application will be with a single dose of 0.3 mg and second application will be single dose of 3 mg. |
| Cohort 2 Part A | EXPERIMENTAL | Subjects with diabetic foot ulcer (DFU) will receive a single application of GSK1278863 or placebo (with 6:2 ratio) in two dosing periods separated by 10 days. The first application will be made on intact skin and second application directly on DFU. Dose will be based on wound area and review from previous cohort data. |
| Cohort 3 Part A | EXPERIMENTAL | Subjects with DFU will receive single application of GSK1278863 or placebo directly on DFU. Dose will be based on wound area and review from previous cohort data. |
| Cohort 4 Part A | EXPERIMENTAL | Subjects with DFU will receive a single application of GSK1278863 or placebo (with 6:2 ratio) in two dosing periods separated by 10 days. The first application will be made on DFU and second application on intact skin. Dose will be based on wound area and review from previous cohort data. |
| Cohort 5 Part B | EXPERIMENTAL | Subjects with DFU will receive Standard of care (SOC) up to 15 days and then will be randomized to one of the three arms: GSK1278863 + SOC, or SOC only, or placebo + SOC with ratio of 12:2:2. Doses for the cohorts in Part B will be determined from safety, tolerability and PK data from Part A. subjects will first be given a single application of GSK1278863 or placebo at the dose chosen for that cohort, followed by a 7-day washout period, and then repeat applications for 14 days, starting on Day 8. |
| Cohort 6 Part B | EXPERIMENTAL | Subjects with DFU will receive Standard of care (SOC) up to 15 days and then will be randomized to one of the three arms: GSK1278863 + SOC, or SOC only, or placebo + SOC with ratio of 12:2:2. Doses for the cohorts in Part B will be determined from safety, tolerability and PK data from Part A. subjects will first be given a single application of GSK1278863 or placebo at the dose chosen for that cohort, followed by a 7-day washout period, and then repeat applications for 14 days, starting on Day 8. |
| Cohort 7 Part B | EXPERIMENTAL | Subjects with DFU will receive Standard of care (SOC) up to 15 days and then will be randomized to one of the three arms: GSK1278863 + SOC, or SOC only, or placebo + SOC with ratio of 12:2:2. Doses for the cohorts in Part B will be determined from safety, tolerability and PK data from Part A. subjects will first be given a single application of GSK1278863 or placebo at the dose chosen for that cohort, followed by a 7-day washout period, and then repeat applications for 14 days, starting on Day 8. |
| GSK1278863 5mg | EXPERIMENTAL | GSK1278863 5mg |
| GSK1278863 100mg | EXPERIMENTAL | GSK1278863 100mg |
| GSK1278863 + food | EXPERIMENTAL | 100 mg of GSK1278863 given with a high fat meal |
| GSK1278863 + Gemfibrozil | EXPERIMENTAL | GSK1278863A 100mg + Gemfibrozil 600mg steady state |
| Name | Type | Description |
|---|---|---|
| GSK1278863 | DRUG | GSK1278863 will be provided as round, standard biconvex, white film coated tablets containing 1 mg, 2 mg, 4 mg or 6 mg of GSK1278863 as active ingredient. |
| Iron | DRUG | Subjects will receive supplemental iron therapy if ferritin is \<=100 ng/mL and TSAT is \<=20%. The investigator (or subinvestigator) will choose the route of administration and dose of prescription iron. |
| GSK1278863 matching Placebo | DRUG | GSK1278863 matching placebo will be supplied as a round, biconvex, 10 mm white film coated tablet. |
| Placebo | DRUG | Film coated tablets of GSK1278863 matching placebo for oral administration. |
| rhEPO | DRUG | rhEPO will be procured from local market |
| GSK1278863 25 mg Tablet | DRUG | A round, biconvex, white film coated tablet to be taken orally in the fasted state in the morning |
| Pioglitazone 15 mg Tablet | DRUG | White to off-white, round, convex, non scored tablet with "ACTOS" on one side, and "15" on the other, to be taken orally in the fasted state in the morning |
| Rosuvastatin 10 mg Tablet | DRUG | Pink, round, biconvex, coated tablets. Debossed "CRESTOR" and "10" on one side, to be taken orally in the fasted state in the morning |
| Trimethoprim 100 mg Tablet | DRUG | White, round, scored, convex tablet, debossed "93" above the score and debossed "2159" below the score on one side and plain on the other, to be taken orally as two tablets once in the morning and once in the evening |
| GSK1278863 75 mg | DRUG | A round, biconvex, white film coated tablet available in two doses (25 and 100 mg) |
| GSK1278863 500 mg | DRUG | A round, biconvex, white film coated tablet available in two doses (25 and 100 mg) |
| Moxifloxacin 400 mg | DRUG | Oblong, dull red, film-coated, convex tablets with M400 on one side |
| Placebo matching GSK1278863 | DRUG | A round, biconvex, white film coated tablet as matching placebo for GSK1278863 |
| Placebo matching Moxifloxacin | DRUG | Capsule shaped white film coated tablet as matching placebo for Moxifloxacin |
| GSK1278863 + food | DRUG | High Fat meal + 100 mg GSK1278863 |
| Gemfibrozil | DRUG | 600 mg Gemfibrozil |
Inclusion Criteria: * Age (at the time of informed consent): \>=20 years * Dialysis: Patients on hemodialysis (HD) or hemodiafiltration (HDF) * Use of any erythropoiesis stimulating agent (ESA): Newly started dialysis (Dialysis newly started \<12 weeks before screening): Patients not using ESAs aft...
GSK1278863 is an investigational small molecule being studied for anemia, wound healing, surgical procedures, tendon injuries, vascular disease, and peripheral vascular disease. It is in Phase 3 clinical development for these hematology-related conditions. The drug has completed 12 clinical trials with a total enrollment of 1,059 participants.
GSK1278863 is being developed by GSK plc, a pharmaceutical company listed on the stock exchange under the ticker GSK. The drug is currently in Phase 3 clinical trials for anemia and other conditions. GSK has conducted 12 completed clinical trials for this investigational compound.
GSK1278863 is in Phase 3 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities. The compound has completed 12 clinical trials, including Phase 1 and Phase 2 studies, and is being evaluated for anemia and other hematology-related conditions.
GSK1278863 has completed 12 clinical trials. Notable studies include NCT01376232, a Phase 1 pharmacokinetic study in India; NCT01673555, a Phase 1 study on pulmonary artery pressure in healthy male volunteers; NCT02135848, a Phase 2 study for peripheral vascular disease; and NCT02371603, a Phase 1 drug-drug interaction study. All trials are completed.
GSK1278863 is an investigational small molecule developed by GSK plc for anemia and other conditions. It is currently in Phase 3 clinical development. The drug has been studied in 12 completed clinical trials, including studies in healthy volunteers and patients with peripheral vascular disease.