Clinical Trial: Safety, Tolerability, Pharmacokinetic (PK), and Pharmacodynamic Study of GSK2881078 and Study to Evaluate the Effect of CYP3A4 Inhibition on PK of GSK2881078

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

Official Title: A Randomized Double-blind (Sponsor Unblind) Placebo Controlled Study in Healthy Subjects to Evaluate: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Repeat Doses of GSK2881078, th

Brief Summary: GSK2881078 is a selective androgen receptor modulator (SARM) that is being evaluated for effects on muscle growth and strength in subjects with muscle wasting to improve their physical function. Part A of this study will evaluate the safety, efficacy and pharmacokinetics of GSK2881078 in healthy, older men and post-menopausal women who will take daily dosing for 28 days and be followed for a total of 70 days. Part B of this study will characterize the effect of Cytochrome P450 3A4 (CYP3A4) inhibition on the GSK2881078 pharmacokinetics. Part B will only be conducted if safe and efficacious dose is identified in Part A. Part A will include healthy older males and post-menopausal females; and randomize approximately 60 subjects (about 15 per cohort [4 cohorts]) to complete approximately 48 (about 12 per cohort). Part B will enroll one cohort of approximately 15 healthy male subjects to complete approximately 12. The study duration will be approximately 115 days for Part A and 122 days for Part B.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Part A: Blood pressure as a measure of safety and tolerability [ Time Frame: Up to Day 70 ]
    Blood pressure will be recorded whilst the subject is in a semi -supine position, having rested in this position for at least 10 minutes.
  • Part A: Heart rate as a measure of safety and tolerability [ Time Frame: Up to Day 70 ]
    Heart rate will be recorded whilst the subject is in a semi -supine position, having rested in this position for at least 10 minutes.
  • Part A: Cardiac telemetry as a measure of safety and tolerability [ Time Frame: Up to Day 28 ]
    Continuous cardiac telemetry will be performed for at least 8 hours post-dose.
  • Part A: Electrocardiogram (ECG) as a measure of safety and tolerability [ Time Frame: Up to Day 70 ]
    Triplicate or single 12-lead ECGs will be obtained at each timepoint and will be recorded whilst the subject is in a semi-supine position, having rested in this position for at least 10 minutes.
  • Part A: Composite of clinical laboratory parameters including hematology, clinical chemistry, and lipid blood panel (fasting) as a measure of safety and tolerability [ Time Frame: Up to Day 70 ]
  • Part A: Number of subjects with adverse events (AEs) [ Time Frame: Up to Day 70 ]
    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 medi

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Part A: Change from baseline in appendicular mass as assessed by Dual-energy X-ray Absorptiometry (DXA) [ Time Frame: Baseline and up to Day 70 ]
      Appendicular lean mass will be calculated from the regional lean mass measurements of the arms and legs.
    • Part A: Change from baseline in total lean mass as assessed by DXA [ Time Frame: Baseline and up to Day 70 ]
      Output from DXA will be used to measure total lean mass.
    • Part A: Change from baseline in thigh muscle volume as assessed by MRI [ Time Frame: Baseline and up to Day 70 ]
      MRI cross-sectional thigh scans will be performed for each cohort in Part A of the study.


    Original Secondary Outcome: Same as current

    Information By: GlaxoSmithKline

    Dates:
    Date Received: September 3, 2015
    Date Started: September 2015
    Date Completion:
    Last Updated: March 2, 2017
    Last Verified: March 2017