GSK2647544 RD, DDI in Healthy Young and Elderly Volunteers

• Status: Terminated
• Trial end date: 2014-03-03
• Target enrollment: 0
• Participant gender: All

Summary

GSK2647544 is an orally available, selective inhibitor of Lp PLA2 that is being developed for the treatment of Alzheimer's disease. The current study is a single-blind, randomised, placebo-controlled, 4-cohort study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of repeat doses of GSK2647544. Cohorts 1, 2 and 3 will evaluate escalating doses of GSK2647544 in young healthy volunteers for 7 days, 7 days, and 14 days, respectively. Cohort 4 will evaluate repeat doses of GSK2647544 in healthy elderly volunteers for 14 days. Additionally, Cohorts 1 and 3 will include an assessment of potential drug-drug interaction with simvastatin to examine CYP3A4 inhibition by GSK2647544.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: GlaxoSmithKline
• Treatments: Simvastatin

Criteria

Inclusion Criteria:

• Males and females who are 18 to 64 years of age inclusive, defined as young subjects in this study, are eligible for Cohorts 1-3 only

• Males and females who are ≥65 years of age, defined as elderly subjects in this study, are eligible for Cohort 4 only

• Healthy as determined by a responsible and experienced physician

• A female subject is eligible to participate if she is of non-childbearing potential

• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods

• Body weight > 50 kg (110 pounds) and body mass index (BMI) between 19 and 32

• Aspartate aminotransferase (AST), Alanine transaminase (ALT), alkaline phosphatase and bilirubin <= 1.5xUpper Limit of Normal (ULN)

• Average of triplicate QTcB values and average of triplicate QTcF values must both < 450 msec

• Capable of giving written informed consent

Exclusion Criteria:

• Subjects with Lp-PLA2 activity <=20 nanomole/minute/milliliter (mL)(for subjects with 2 known birth parents of at least 50% Japanese, Chinese, or Korean ancestry)

• History of asthma, anaphylaxis or anaphalactoid reactions, severe allergic responses

• History of hypercoagulable state or history of thrombosis

• History of biliary tract disease including a history of liver disease with elevated liver function tests of known or unknown etiology

• Positive Human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C at screening

• History of regular use of tobacco or nicotine-containing products within 6 months of the study

• Unable to abstain from alcohol or caffeine or xanthine-containing products for 24 h prior to the start of dosing

• Unable to refrain from use of prescription or non-prescription drugs and vitamins within 7 days or 5 half-lives (whichever is longer) prior to administration of study

• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening (Note: This applies to healthy young subjects screened for Cohorts 1-3 only. Healthy elderly subjects for cohort 4 who are social smokers must give up smoking for the period that they will be on the unit)

• positive pre-study drug/alcohol screen

• Unable to refrain from consumption of Seville oranges, grapefruit or grapefruit juice within 7 days prior to the first dose of study medication until the follow-up visit

• Subjects who have taken statins, medicines that are contraindications of statins, know potent inhibitiors or inducers of CYP3A4 in the 4 weeks or 5 half-lives (whichever is longer) prior to screening and are not able to discontinue use throughout participation in the clinical trial