Clinical Trial: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2849466 in Healthy Male Subjects

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Single-center, Randomized, Blinded, Placebo-controlled Two-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Selective Androgen Receptor Modulator (SARM)

Brief Summary: This study is the first administration of GSK2849466 in humans. This will be a single centre, randomized, double-blind, placebo-controlled study, to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK2849466, given as single and repeat oral doses up to 14 days to healthy male subjects. Part A will be a randomized placebo controlled and 4-way crossover study. It will include two cohorts of 8 subjects each. In each cohort there will be 4 study periods each approximately of 1 week including 6 days of washout. Each subject will receive a total of 3 active doses as ascending single oral dose of GSK2849466 and 1 placebo dose during the course of their participation in the study. The first ("bridging dose") dose provided to subjects in Cohort 2 will be the same as the last dose provided to subjects in Cohort 1. The single doses of GSK2849466 planned in Part A of this study are: 0.01, 0.03, 0.1, and 0.3 milligram (mg) in Cohort 1 and 0.3, 1, 3, and 10 mg in Cohort 2. In cohorts 1 and 2 all available safety, tolerability, and PK data will be reviewed prior to each dose escalation. The dosing schedule in Part A may be adjusted to expand a cohort or to add an additional cohort(s) in order to further evaluate additional doses or repeat evaluation of a dose level already studied. Part B will be a randomized placebo controlled, parallel group study. It will include three cohorts of 12 subjects each. Each subject will receive repeat doses of GSK2849466 over 14 days. The doses chosen for Part B will be based on the safety, tolerability, and PK data from Part A. Subjects in Cohort 4 (and/or an another cohort [s] as determined based on Part A PK data) will be dosed in the fasted state on Days 1 and 14 and in the fed state on Day 7 when subjects will receive a standard meal 30 minutes prior to dosing. Part B will provide sufficient safety and tolerability data to bridge to longer duration studies. The study duration, including screen

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Safety and tolerability of single ascending doses GSK2849466 as assessed by number of subjects with adverse events (AE)s [ Time Frame: 28 days ]
    Safety and tolerability parameters will include recording of AEs, throughout the study.
  • Safety and tolerability of repeat doses of GSK2849466 as assessed by number of subjects with AEs [ Time Frame: 14 days ]
    Safety and tolerability parameters will include recording of AEs, throughout the study.
  • Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in electrocardiogram (ECG) readings [ Time Frame: 28 days ]
    Safety and tolerability parameter will include the ECG readings at Baseline and at end of the study.
  • Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in ECG readings [ Time Frame: 14 days ]
    Safety and tolerability parameter will include the ECG readings at Baseline and at end of the study.
  • Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in clinical monitoring of blood pressure [ Time Frame: 28 days ]
    Safety and tolerability parameters will include blood pressure readings at Baseline and at end of the study.
  • Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in clinical monitoring of blood pressure [ Time Frame: 14 days ]

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) and AUC from zero to infinity (AUC(0-inf)) following single doses of GSK2849466 [ Time Frame: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose. ]
      The AUC(0-t) and AUC(0-inf) for GSK2849466 will be assessed following single doses of GSK2849466.
    • Maximum concentration (Cmax) following single doses of GSK2849466 [ Time Frame: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose. ]
      The Cmax of GSK2849466 will be assessed following single doses of GSK2849466.
    • Time to maximum observed plasma drug concentration (Tmax) following single doses of GSK2849466 [ Time Frame: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose. ]
      The Tmax for GSK2849466 will be assessed following single doses of GSK2849466.
    • Terminal half-life (t1/2) following single doses of GSK2849466 [ Time Frame: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose. ]
      The t1/2 for GSK2849466 will be assessed following single doses of GSK2849466.
    • The AUC(0-t), AUC(0-inf)) and AUC from time zero to the end of the dosing interval at steady state AUC(0-tau) following repeat doses of GSK2849466 [ Time Frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7. ]
      The AUC(0-t), AUC(0-inf) and AUC(0-tau) following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
    • The Cmax following repeat doses of GSK2849466 [ Time Frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7. ]
      The Cmax following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
    • The Tmax following repeat doses of GSK2849466 [ Time Frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7. ]
      The Tmax following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
    • The t1/2 following repeat doses of GSK2849466 [ Time Frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7. ]
      The t1/2 following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
    • The estimation of an accumulation ratio following repeat doses of GSK2849466 [ Time Frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7. ]
      The estimation of an accumulation ratio following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.


    Original Secondary Outcome: Same as current

    Information By: GlaxoSmithKline

    Dates:
    Date Received: September 27, 2012
    Date Started: September 2012
    Date Completion:
    Last Updated: November 18, 2016
    Last Verified: November 2016