Clinical Trial: A Study to Evaluate Single and Repeat Doses of IV GSK2251052 in Healthy Male Japanese and Caucasian Subjects and Repeat Doses of Supratherapeutic Doses of IV GSK2251052 in Healthy Volunteers

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Two Part Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK2251052 After Single Ascending Doses and Repeat Doses of IV GSK2251052 in Healthy Male Japanese and Caucasian Subjects

Brief Summary:

This is a two-part study. Part A is a three-period study in approximately 24 healthy male Japanese and Caucasian subjects. Period 1 and Period 2 will be an open label study to investigate the safety, tolerability, and pharmacokinetics of single ascending intravenous doses of GSK2251052. Period 3 is a single blind, placebo controlled, repeat fixed dose design to evaluate the safety, tolerability and pharmacokinetics of multiple intravenous doses of GSK2251052 for 12 days. The selection of the repeat IV dose will be based on the results from Periods 1 and 2. Japanese subjects will be stratified based on their metabolic genotype, polymorphic or wild-type for ADH and ALDH. Caucasian subjects are not anticipated to have these enzyme polymorphisms and therefore will not be stratified.

Part B is a two cohort, single-blind, randomized, placebo-controlled, dose-rising, repeat dose study in approximately 24 healthy male and female subjects to evaluate the safety, tolerability, and pharmacokinetics of supratherapeutic IV doses of GSK2251052 for 10 days. Cohort 1 subjects will be randomized to receive 2250 mg of GSK2251052 or placebo and Cohort 2 subjects will be randomized to receive 3000 mg GSK2251052 or placebo. The decision to conduct Cohort 2 of Part B will be based on the available toxicology cover results from ongoing preclinical toxicity studies.


Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Composite (or Profile) of Pharmacokinetics [ Time Frame: Part A: Period 1 for 168 hours post dose; Period 2 for 336 hours post dose; Period 3 on day 12 for 12 hours post dose. Part B: On day 1 for 72 hours post dose; on day 12 for 12 hours post dose. ]
    pharmacokinetic endpoints maximum observed concentration fixed nominal time (Cmax), area under the concentration-time curve from time zero extrapolated to infinite time (AUC(0-∞), area under the concentration-time curve from time zero to last time of quantifiable concentration within a subject across all treatments (AUC(0-t), AUC(0-12), time of occurrence of Cmax (tmax), time of last quantifiable concentration (tlast), terminal phase half-life (t1/2), volume of distribution at steady state (Vss), and Systemic clearance of parent drug (CL) of GSK2251052 and metabolite M3 (as appropriate).
  • Safety and tolerability parameters including change from baseline measures for vital signs [ Time Frame: Part A: for 15 weeks. Part B: for 9 weeks ]
  • Safety and tolerability parameters including change from baseline for ECGs [ Time Frame: Part A: for 15 weeks. Part B: for 9 weeks ]
  • Safety and tolerability parameters including change from baseline for clinical laboratory tests [ Time Frame: Part A: for 15 weeks. Part B: for 9 weeks ]
    hematology, chemistry, and urinalysis
  • Safety and tolerability parameters including change from baseline in the collection of adverse events [ Time Frame: Part A: for 15 weeks. Part B: for 9 weeks ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Composite (or Profile) of Pharmacokinetics [ Time Frame: Part A: Period 1 for 168 hours post dose; Period 2 for 336 hours post dose; Period 3 on day 12 for 12 hours post dose. Part B: On day 1 for 72 hours post dose; on day 12 for 12 hours post dose. ]
    Observed accumulation based on (AUC(Ro) and Cmax (RCmax) and determine the steady-state ratio (Rss)
  • Composite or Profile of Pharmacokinetics [ Time Frame: Part A: Period 1 for 168 hours post dose; Period 2 for 336 hours post dose; Period 3 on day 12 for 12 hours post dose. Part B: On day 1 for 72 hours post dose; on day 12 for 12 hours post dose. ]
    AUC(0-∞), AUC(0-t), and Cmax following IV administration at different doses for the assessment of dose proportionality


Original Secondary Outcome: Same as current

Information By: GlaxoSmithKline

Dates:
Date Received: December 15, 2011
Date Started: December 2011
Date Completion:
Last Updated: July 19, 2012
Last Verified: July 2012