gsk2647544 rd, ddi in healthy young and elderly volunteers

Conditions: Alzheimer's Disease

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.


Eligibility 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

Keywords: alzheimer's disease gsk2647544 drug-drug interaction healthy subjects lp-pla2 simvastatin