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A Study to Investigate the Pharmacokinetics (PK) of Modified Release (MR) Prototype Coated Tablet Formulations of GSK2982772

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03649412
Recruitment Status : Completed
First Posted : August 28, 2018
Results First Posted : May 1, 2020
Last Update Posted : May 1, 2020
Sponsor:
Collaborator:
Quotient Sciences
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE August 24, 2018
First Posted Date  ICMJE August 28, 2018
Results First Submitted Date  ICMJE April 8, 2020
Results First Posted Date  ICMJE May 1, 2020
Last Update Posted Date May 1, 2020
Actual Study Start Date  ICMJE September 26, 2018
Actual Primary Completion Date May 7, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2020)
  • Part A: Area Under the Curve From Time Zero to Infinity (AUC[0-inf]) of GSK2982772 240 mg in IR Formulation [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose ]
    Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis. PK parameters were analyzed using standard non-compartmental analysis. Participants in the 'Safety Population (all participants who received at least one dose of study treatment)' for whom a PK sample was obtained and analyzed were part of PK Population.
  • Part A: AUC(0-inf) of GSK2982772 240 mg in MR Coated Tablet Formulation [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected from participants at indicated time points for PK analysis. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: AUC(0-inf) of GSK2982772 240 mg in MR Coated Tablet Formulation After High-fat Breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected from participants at indicated time points for PK analysis. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of GSK2982772 240 mg for IR Formulation [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: AUC(0-t) of GSK2982772 240 mg for MR Coated Tablet Formulation [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: AUC(0-t) of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: Area Under the Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK2982772 240 mg for IR Formulation [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24). PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: AUC(0-24) of GSK2982772 240 mg for MR Coated Tablet Formulation [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24). PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: AUC(0-24) of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24). PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: Maximum Observed Concentration (Cmax) of GSK2982772 240 mg for IR Formulation [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: Cmax of GSK2982772 240 mg for MR Coated Tablet Formulation [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: Cmax of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: Concentration at 24 Hours Post-dose (C24h) of GSK2982772 240 mg for IR Formulation [ Time Frame: 24 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: C24h of GSK2982772 240 mg for MR Coated Tablet Formulation [ Time Frame: 24 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: C24h of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast [ Time Frame: 24 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: Time to Cmax (Tmax) of GSK2982772 240 mg for IR Formulation [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: Tmax of GSK2982772 240 mg for MR Coated Tablet Formulation [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: Tmax of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: Terminal Half-life (t1/2) of GSK2982772 240 mg for IR Formulation [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: t1/2 of GSK2982772 240 mg for MR Coated Tablet Formulation [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours ]
    Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: t1/2 of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours ]
    Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis.
  • Part B: AUC(0-inf) of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for AUC(0-inf). PK parameters were analyzed using standard non-compartmental analysis.
  • Part B: AUC(0-t) of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for AUC(0-t). PK parameters were analyzed using standard non-compartmental analysis.
  • Part B: Cmax of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis.
  • Part B: C24h of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast [ Time Frame: 24 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis.
  • Part B: Tmax of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis.
  • Part B: t1/2 of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis.
  • Part A: Relative Bioavailability in Fed Versus Fasted Conditions (FrelFE) Based on AUC(0-inf) of GSK2982772 for MR Coated Tablet Formulation [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected at indicated time points for analysis of FrelFE based on AUC of GSK2982772. Frel for AUC(0-inf) was calculated as Geometric mean of AUC(0-inf) of MR Fed/ Geometric mean of AUC(0-inf) of MR Fasted multiplied by 100.
  • Part A: FrelFE Based on AUC(0-t) of GSK2982772 for MR Coated Tablet Formulation [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected at indicated time points for analysis of FrelFE based on AUC of GSK2982772. Frel for AUC(0-t) was calculated as Geometric mean of AUC(0-t) of MR Fed/Geometric mean of AUC(0-t) of MR Fasted multiplied by 100.
  • Part A: FrelFE Based on Cmax of GSK2982772 for MR Coated Tablet Formulation [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected at indicated time points for analysis of FrelFE based on Cmax of GSK2982772. Frel for Cmax was calculated as Geometric mean of Cmax of MR Fed/Geometric mean of Cmax of MR Fasted multiplied by 100.
  • Part B: FrelFE of GSK2982772 Based on AUC(0-inf) for MR Coated Tablet Formulation in Fed vs Fasted State [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected at indicated time points for analysis of FrelFE based on AUC(0-inf) of GSK2982772. Frel for AUC(0-inf) was calculated as Geometric mean of AUC(0-inf) of MR Fed/ Geometric mean of AUC(0-inf) of MR Fasted multiplied by 100.
  • Part B: FrelFE of GSK2982772 Based on AUC (0-t) for MR Coated Tablet Formulation in Fed vs Fasted State [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected at indicated time points for analysis of FrelFE based on AUC (0-t) of GSK2982772. FrelFE for AUC (0-t) was calculated as Geometric mean of AUC (0-t) of MR Fed/ Geometric mean of AUC (0-t) of MR Fasted multiplied by 100.
  • Part B: FrelFE of GSK2982772 Based on Cmax for MR Coated Tablet Formulation in Fed vs Fasted State [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected at indicated time points for analysis of FrelFE based on Cmax of GSK2982772. FrelFE for Cmax was calculated as Geometric mean of Cmax of MR Fed/ Geometric mean of Cmax of MR Fasted multiplied by 100.
  • Part B: Frel of GSK2982772 Based on AUC (0-inf) for MR Coated Tablet Formulation in Fasted State [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected at indicated time points for analysis of Frel (dose) based on AUC (0-inf) of GSK2982772. Frel (dose) for AUC (0-inf) was calculated as Geometric mean of AUC (0-inf) of MR formulation (test dose) Fasted/ Geometric mean of AUC (0-inf) of MR Fasted formulation (reference dose) multiplied by 100.
  • Part B: Frel of GSK2982772 Based on AUC (0-t) for MR Coated Tablet Formulation in Fasted State [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected at indicated time points for analysis of Frel (dose) based on AUC(0-t) of GSK2982772. Frel (dose) for AUC(0-t) was calculated as Geometric mean of AUC(0-t) of MR formulation (test dose) Fasted/ Geometric mean of AUC(0-t) of MR Fasted formulation (reference dose) multiplied by 100.
  • Part B: Frel of GSK2982772 Based on AUC (0-24) for MR Coated Tablet Formulation in Fasted State [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose ]
    Blood samples were collected at indicated time points for analysis of Frel (dose) based on AUC(0-24) of GSK2982772. Frel (dose) for AUC(0-24) was calculated as Geometric mean of AUC(0-24) of MR formulation (test dose) Fasted/Geometric mean of AUC(0-24) of MR Fasted formulation (reference dose) multiplied by 100.
  • Part B: Frel of GSK2982772 Based on Cmax for MR Coated Tablet Formulation in Fasted State [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected at indicated time points for analysis of Frel dose. Frel for Cmax was calculated as Geometric mean of Cmax of MR formulation (test) Fasted/ Geometric mean of Cmax of MR Fasted Formulation (reference dose) multiplied by 100.
  • Part A: Relative Bioavailability (Frelformulation) Based on AUC (0-inf) of GSK2982772 240 mg [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose ]
    Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC(0-inf) of GSK2982772 in fasted state. Frel for AUC(0-inf) was calculated as Geometric mean of AUC(0-inf) of MR formulation (test) Fasted/ Geometric mean of AUC(0-inf) of Fasted of IR Formulation (reference) multiplied by 100.
  • Part A: Frelformulation Based on AUC (0-t) of GSK2982772 for MR Coated Tablet Formulation (240 mg) [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours ]
    Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 in fasted state. Frel for AUC (0-t) was calculated as Geometric mean of AUC(0-t) of MR Fasted formulation (test) / Geometric mean of AUC(0-t) of Fasted of IR Formulation (reference) multiplied by 100.
  • Part A: Frelformulation Based on AUC(0-24) of GSK2982772 for MR Coated Tablet Formulation (240 mg) [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours ]
    Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 in fasted state. Frel for AUC(0-24) was calculated as Geometric mean of AUC(0-24) of MR Fasted formulation (test) / Geometric mean of AUC(0-24) of Fasted of IR Formulation (reference) multiplied by 100.
  • Part A: Frelformulation Based on Cmax of GSK2982772 for MR Coated Tablet Formulation (240 mg) [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours ]
    Blood samples were collected at indicated time points for analysis of Frelformulation based on Cmax of GSK2982772 in fasted state. Frel for Cmax was calculated as Geometric mean of Cmax of MR Fasted formulation (test) / Geometric mean of Cmax of Fasted Formulation of IR formulation (reference) multiplied by 100.
Original Primary Outcome Measures  ICMJE
 (submitted: August 24, 2018)
  • Part A- Area under the curve from time zero to infinity (AUC [0-inf]) for GSK2982772, MR coated tablet formulation [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- AUC (0-inf), for GSK2982772, for immediate release (IR) formulations [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours in treatment period 3 ]
    Serial blood samples will be collected at specified time points.
  • Part A- AUC from time zero to the last measurable concentration (AUC[0-t]), for GSK2982772, MR coated tablet formulation [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- AUC(0-t), for GSK2982772, IR formulation [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours in treatment period 3 ]
    Serial blood samples will be collected at specified time points.
  • Part A- AUC from time zero to 24 hours (AUC[0-24]), for GSK2982772, MR coated tablet formulation [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- AUC (0-24), for GSK2982772, for IR formulations [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours in treatment period 3 ]
    Serial blood samples will be collected at specified time points.
  • Part A- Maximum observed concentration (Cmax) for GSK2982772, MR coated tablet formulation [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- Cmax for GSK2982772, for IR formulations [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours in treatment period 3 ]
    Serial blood samples will be collected at specified time points.
  • Part A- Concentration at 24 hours post-dose (C24h) for MR coated tablet formulation [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- C24h for IR coated tablet formulation [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours in treatment period 3 ]
    Serial blood samples will be collected at specified time points.
  • Part A- Time to Cmax (Tmax), for GSK2982772, for MR coated tablet formulation [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- Tmax for GSK2982772 for IR coated tablet formulation [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours in treatment period 3 ]
    Serial blood samples will be collected at specified time points.
  • Part A- terminal half-life (t1/2) for GSK2982772, for MR coated tablet formulation [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- t1/2 for GSK2982772, for IR coated tablet formulation [ Time Frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours in treatment period 3 ]
    Serial blood samples will be collected at specified time points.
  • Part A- AUC(0-inf) for GSK2982772, following a single dose administration for selected MR prototype coated tablet formulation, with impact of high-fat breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part B- AUC(0-inf) for GSK2982772, post single dose administration for selected MR prototype coated tablet formulation, with impact of high-fat breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- AUC (0-t) for GSK2982772, post single dose administration for selected MR prototype coated tablet formulation, with impact of high-fat breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part B- AUC(0-t) for GSK2982772, post single dose administration for selected MR prototype coated tablet formulation, with impact of high-fat breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- Cmax for GSK2982772, post single dose administration for selected MR prototype coated tablet formulation, with impact of high-fat breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part B- Cmax for GSK2982772, post single dose administration for selected MR prototype coated tablet formulation, with impact of high-fat breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- Tmax for GSK2982772, post single dose administration for selected MR prototype coated tablet formulation, with impact of high-fat breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part B- Tmax for GSK2982772, post single dose administration for selected MR prototype coated tablet formulation, with impact of high-fat breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- C24h for GSK2982772, post single dose administration for selected MR prototype coated tablet formulation, with impact of high-fat breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part B- C24h for GSK2982772, post single dose administration for selected MR prototype coated tablet formulation, with impact of high-fat breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- t1/2 for GSK2982772, post single dose administration for selected MR prototype coated tablet formulation, with impact of high-fat breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part B- t1/2 for GSK2982772, post single dose administration for selected MR prototype coated tablet formulation, with impact of high-fat breakfast [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- relative bioavailability (FrelFE) for GSK2982772 in fed vs fasted conditions [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part B- FrelFE for GSK2982772 in fed vs fasted conditions [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part A- relative bioavailability (FrelMRFormulation) of GSK2982772 MR prototype coated tablet formulation relative to each other [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
  • Part B- FrelMRFormulation of GSK2982772 MR prototype coated tablet formulation relative to each other [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2020)
  • Part A: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 67 ]
    An AE is any untoward medical occurrence in a clinical study participants, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events that may jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed before.
  • Part A: Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria [ Time Frame: Up to Day 67 ]
    Clinical chemistry parameters with PCI values:albumin (low: <30 millimoles per liter[mmol/L]), Alanine transaminase (ALT) (high: >=2xupper limit of normal [ULN]), Aspartate Aminotransferase(AST) (high: >=2xULN), Alkaline phosphatase(ALP) (high:>=2xULN), calcium(low: <2 mmol/L, high: >2.75 mmol/L),creatinine (high: >44.2 mmol/L),glucose (low: <3 mmol/L,high: >9 mmol/L), potassium (low: <3 mmol/L,high: >5.5 mmol/L),sodium (low: <130 mmol/L,high: >150 mmol/L),total bilirubin(high :>= 1.5xULN). Participants are counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High),or whose value became normal, are recorded in the "To Normal or No Change" category. Participants are counted twice if the participants has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Data for worst-case post-Baseline has been reported.
  • Part A: Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria [ Time Frame: Up to Day 67 ]
    Hematology parameters with PCI ranges: hematocrit (high: >0.54 percentage of red blood cells), hemoglobin (high: >180 grams per liter [g/L]), lymphocytes (low: <0.8*giga cells per liter [10^9/L]), total neutrophil count (low: <1.5*10^9/L), platelet count (low: <100*10^9/L and high: >550*10^9/L), and while blood cell (WBC) count (low: <3*10^9/L and high: >20*10^9/L). Participants are counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Data for worst-case post-Baseline has been reported.
  • Part A: Number of Participants With Abnormal Urinalysis Dipstick Results [ Time Frame: Day 2 (post-dose) ]
    Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination was performed abnormal data for red blood cells (RBC): 1-9 High potential field (HPF) and WBC: 1-9/ HPF; WBC: 10-50/HPF has been presented.
  • Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in IR Formulation [ Time Frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours ]
    SBP and DBP were measured in a semi-supine position after 5 minutes of rest of the participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Part A: Change From Baseline in SBP and DBP in MR Formulation [ Time Frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours, Day 3: 48 hours ]
    SBP and DBP were measured in a semi-supine position after 5 minutes of rest of the participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Part A: Change From Baseline in Heart Rate in IR Formulation [ Time Frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours ]
    Heart rate was measured in a semi-supine position after 5 minutes of rest of participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Part A: Change From Baseline in Heart Rate in MR Formulation [ Time Frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours, Day 3: 48 hours ]
    Heart rate was measured in a semi-supine position after 5 minutes of rest of participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Part A: Change From Baseline in Respiration Rate in IR Formulation [ Time Frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours ]
    Respiratory rate was measured in a semi-supine position after 5 minutes of rest of the participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Part A: Change From Baseline in Respiration Rate in MR Formulation [ Time Frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours, Day 3: 48 hours ]
    Respiratory rate was measured in a semi-supine position after 5 minutes of rest of the participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Part A: Change From Baseline in Body Temperature in IR Formulation [ Time Frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours ]
    Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Part A: Change From Baseline in Body Temperature in MR Formulation [ Time Frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours, Day 3: 48 hours ]
    Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in IR Formulation [ Time Frame: Up to Day 67 ]
    Single 12-lead ECGs were obtained using an automated ECG machine that calculated PR, QRS, QT and Corrected QT (QTc) intervals. ECG measurements were performed in a semi-supine or supine position. Number of participants with abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for worst-case post-Baseline has been reported.
  • Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in MR Formulation [ Time Frame: Up to Day 67 ]
    Single 12-lead ECGs were obtained using an automated ECG machine that calculated PR, QRS, QT and Corrected QT (QTc) intervals. ECG measurements were performed in a semi-supine or supine position. Number of participants with abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for worst-case post-Baseline has been reported.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 24, 2018)
  • Part A- Number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 12 weeks ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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, is a congenital anomaly/ birth defect and other situations which involve medical or scientific judgment.
  • Part A- Number of subjects with abnormal clinical chemistry values [ Time Frame: Up to 12 weeks ]
    Blood samples will be collected to measure blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, magnesium, potassium, chloride, calcium, triglycerides, Aspartate aminotransferase (AST), ALT, alkaline phosphatase, total and direct bilirubin, albumin, and total protein.
  • Part A- Number of subjects with abnormal hematology parameters [ Time Frame: Up to 12 weeks ]
    Blood samples will be collected to measure platelets, white blood cell (WBC count), red blood cell (RBC) count, reticulocyte count, hemoglobin, hematocrit, RBC indices, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), basophils, eosinophil's, lymphocytes, monocytes and neutrophils.
  • Part A- Number of subjects with abnormal urinalysis [ Time Frame: Up to 12 weeks ]
    Urine samples will be collected to measure specific gravity, potential of hydrogen (pH), glucose, protein, blood, bilirubin, urobilinogen, nitrite, leukocytes and ketones by dipstick method at specified time points.
  • Part A- Number of subjects with abnormal vital signs [ Time Frame: Up to 12 weeks ]
    The number of subjects with abnormal vital signs, in a semi-supine position after 5 minutes rest and will include systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature, systolic and diastolic blood pressure, heart rate and respiratory rate.
  • Part A- Number of subjects with abnormal 12-Lead electrocardiogram (ECG) findings [ Time Frame: Up to 12 weeks ]
    Twelve-lead ECGs, will be performed, with the subject at designated time points, using an ECG machine, after 5 minutes of rest. The number of subjects with abnormal ECG values will be reported.
  • Part A- Relative bioavailability (Frelformulation) of GSK2982772 (under fed or fasted conditions) vs IR reference formulation [ Time Frame: Pre-dose, 2, 4, 6, 8 , 10 , 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours in treatment period 1, 2, 4, 5 and 6 ]
    Serial blood samples will be collected at specified time points.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Investigate the Pharmacokinetics (PK) of Modified Release (MR) Prototype Coated Tablet Formulations of GSK2982772
Official Title  ICMJE A Two Part, Non-randomised, Open Label Study Designed to Assess the Pharmacokinetic Profile of Modified Release Prototype Coated Tablet Formulations of GSK2982772 Relative to an Immediate Release Reference Tablet Formulation at a Fixed Strength (Part A) and the Pharmacokinetic Profile of Alternative Tablet Strengths of the Selected Modified Release Prototype Coated Tablet Formulation (Part B, Optional) in Healthy Participants
Brief Summary Previous clinical studies of immediate release (IR) formulations of GSK2982772 resulted in a high peak to trough ratio of GSK2982772. Additionally, the short half-life for GSK2982772 (approximately 2 to 3 hours) necessitates twice a daily (BID) or thrice daily (TID) dosing of an IR formulation. As a result, MR formulations using a polymer matrix approach with minitablets in capsule and MR tablet formulations were investigated. The emerging PK data of the MR formulations investigated to date have demonstrated that a once daily (QD) PK profile can be achieved in the fasted state but the polymer matrix formulation is susceptible to food effects when administered with a high fat breakfast. The purpose of this study is to evaluate MR prototype coated tablet formulations. This study will evaluate the PK of MR prototype coated tablet formulations of GSK2982772. The study is divided into two parts; Part A and Part B. The MR tablet coating used in Part A and the initial periods of Part B will have an aperture drilled into the enteric coating of either side of the tablet. This allows some drug release to commence in the stomach whilst providing controlled release throughout the gastrointestinal (GI) tract. In Part B only, a new investigational medicinal product (IMP) will be manufactured to allow comparison of the tablet coating either with apertures (i.e., drilled) or without apertures (i.e., full coat/non drilled). Part A will be a 6-period, 6-way fixed sequence design, up to 4 MR tablet prototype coated formulations will be evaluated in fasted state at 240 milligrams (mg). Periods 1, 2 and 3 will evaluate MR1, IR tablet and MR2 respectively. Periods 4, 5 and 6 will be flexible and the dosing regimen will be dependent on the outcome of Periods 1 to 3. In addition, the impact of food (high fat meal, standard breakfast or administration 30 or 60 minutes before a standard breakfast) on selected MR prototype coated tablet formulations may also be evaluated in Period 4, 5 or 6 of Part A. Each inpatient period for MR regimens (Periods 1, 3, 4 to 6) will consist of 4 days and 3 nights, and the inpatient period for the IR tablet (Period 2) will consist of 3 days and 2 nights. There will be a minimum washout of 7 days between doses, and a follow-up visit will occur at 7 to 9 days after the last study treatment. The Part B of the study will be a 7-period fixed sequence which will evaluate the selected MR prototype coated tablet formulation(s) at different tablet strengths or as multiple unit doses and with or without apertures in the tablet coatings. There will be an interim review after each period 1 to 5 of Part B to select the dose level, formulation and prandial status for each subsequent period. An interim data review after Part B Period 6 will determine if optional Period 7 is required and the dose level, dosing time (morning or evening), formulation and prandial status for that period. Each inpatient period will consist of a 4-day and 3-night with a minimum of 7 days washout between doses. A follow-up visit will occur at 7 to 9 days after the last study treatment. Approximately 33 subjects will be enrolled in the study. The total duration for Part A will be approximately 10-12 weeks and 10-14 weeks for Part B (including screening period of approximately 4 weeks).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Part A will be a 6-period, 6-way fixed sequence design, in which up to 4 MR tablet prototype coated formulation will be evaluated, following single dose administration (240 mg) in fasted or fed state. There will be a minimum 7-day washout between doses. Part B of the study is optional. Following the final period of Part A, there will be an interim review to determine whether to proceed with optional Part B, and if so, the formulations and tablet strengths to be investigated in Part B. The Part B of the study will be a 7-period fixed sequence which will evaluate the selected MR prototype coated tablet formulation(s) at different tablet strengths or as multiple unit doses.
Masking: None (Open Label)
Masking Description:
There will be no masking as this is an open-label study.
Primary Purpose: Treatment
Condition  ICMJE Autoimmune Diseases
Intervention  ICMJE
  • Drug: GSK2982772 Modified Release
    GSK2982772 MR will be available as MR prototype coated tablet with unit dose strength of 240 mg in Part A. In Part B, GSK2982772 MR prototype coated tablet with unit dose strength of 120 mg (may be changed following interim review of Part B) will be administered by subjects. GSK2982772 MR will be administered orally with 240 milliliter (mL) of water.
  • Drug: GSK2982772 Immediate Release
    In part A, GSK2982772 IR tablet will be available with unit dose strength of 30 mg and the total dose administered by subjects will be 240 mg (8 tablets of dose strength 30 mg) orally with 240 mL of water
Study Arms  ICMJE
  • Experimental: Subjects in Part A
    Subjects in Part A will receive GSK2982772 MR (Period 1, 3, 4, 5 and 6) and GSK2982772 IR (Period 2).
    Interventions:
    • Drug: GSK2982772 Modified Release
    • Drug: GSK2982772 Immediate Release
  • Experimental: Subjects in Part B
    Subjects in Part B will receive GSK2982772 MR.
    Intervention: Drug: GSK2982772 Modified Release
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 17, 2019)
33
Original Estimated Enrollment  ICMJE
 (submitted: August 24, 2018)
32
Actual Study Completion Date  ICMJE May 7, 2019
Actual Primary Completion Date May 7, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subject at the time of participation must be 18 to 65 years of age.
  • Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
  • Body weight greater than or equal to 50 kilogram (kg) and body mass index within the range 19.0 to 32.0 kg per squared meter (kg/m^2) (inclusive).
  • Male or female subjects where male subjects are eligible to participate if they agree to the following during the intervention period until completion of the final follow up visit after the last dose of study treatment; refrain from sperm donation; plus either be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception/barrier like use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant; agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person.
  • The eligible female subjects can participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP); is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of less than 1 percentage per year), preferably with low user dependency, for at least 30 days before first dose until completion of the final follow up visit after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction from Day 1 until 3 months after the last dose. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention; a WOCBP must have a negative highly sensitive serum pregnancy test within 24 hours before the first dose of study intervention; additional requirements for pregnancy testing during and after study intervention must be followed; the investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • Capable of giving an Informed Consent.

Exclusion Criteria:

  • History of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
  • Any history of suicidal behavior within the past 6 months or any history of attempted suicide in subject's lifetime.
  • History of clinically significant psychiatric disorders as judged by the investigator. Depression requiring treatment in the last 2 years.
  • History of herpes zoster (shingles) reactivation.
  • History or diagnosis of obstructive Sleep Apnea.
  • History of a significant respiratory disorder. Childhood asthma that has fully resolved is permitted.
  • History or current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
  • A positive diagnostic tuberculosis (TB) test at screening defined as a positive QuantiFERON-TB Gold test or T-spot test. In cases where the QuantiFERON or T-spot test is indeterminate, the subject may have the test repeated once, but they will not be eligible for the study unless the second test is negative.
  • History of GI surgery (with exception of appendectomy).
  • History of cholecystectomy or gall stones.
  • Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active.
  • Alanine transaminase (ALT) greater than 1.5 times upper limit of normal (ULN).
  • Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percentage of total).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome).
  • Corrected QT interval (QTcF) greater than 450 milliseconds (msec).
  • Past or intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing (paracetamol/acetaminophen [up to 2 gram per day], hormone replacement therapy and hormonal contraception are permitted).
  • Live or attenuated vaccine(s) within 30 days of enrolment, or plans to receive such vaccines during the study or plans to receive a vaccine within 30 days plus 5 half lives, of the last dose of study medication.
  • Participation in the study would result in loss of blood or blood products in excess of 500 mL within a 56 day period; therefore donation or loss of greater than 400 mL of blood within the previous 3 months.
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Current enrolment or past participation within the last 3 months before signing of consent in this or any other clinical study involving an investigational study treatment or any other type of medical research.
  • Subjects who have previously been enrolled in this study. Subjects in Part A of this study are not permitted to participate in Part B.
  • Current or history of renal disease or estimated glomerular filtration rate by chronic kidney disease epidemiology collaboration (CKD-EPI) equation calculation less than 60 milliliter (mL) per minute per 1.73 m^2 at screening.
  • Presence of Hepatitis B surface antigen (HBsAg) at screening. Positive Hepatitis C antibody test result at screening or within 3 months prior to first dose. As potential for and magnitude of immunosuppression with this compound is unknown, subjects with presence of Hepatitis B core antibody (HBcAb) should be excluded. Subjects positive for HBsAg and/or positive for anti-HBc antibody (regardless of anti-HBs antibody status) are excluded.
  • An elevated C-reactive protein (CRP) outside the normal reference range.
  • Confirmed positive pre-study drug/alcohol screen.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • Regular use of known drugs of abuse, or history of drug or alcohol abuse in the past 5 years.
  • Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of greater than 21 units for males or greater than14 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer or 1 (25 mL) measure of spirits, 1.5 to 2 units is 1 glass (125 mL) of wine, depending on type.
  • Current use or history of regular use of tobacco- or nicotine-containing products within 6 months prior to screening. A carbon monoxide breath test reading of greater than 10 parts per million (ppm).
  • Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
  • Subjects who do not have suitable veins for multiple venipuncture's/cannulation as assessed by the investigator at screening.
  • Total cholesterol greater than or equal to 300 mg per deciliter (mg/dL) (greater than or equal to 7.77 millimole per liter [mmol]/L]) or triglycerides greater than or equal to 250 mg/dL (greater than or equal to 2.82 mmol/L).
  • Subjects who are study site or sponsor employees, or immediate family members of a study site or sponsor employee.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03649412
Other Study ID Numbers  ICMJE 209261
2018-002370-48 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available, within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided, after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided, for an initial period of 12 months but an extension can be granted, when justified for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Quotient Sciences
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP