GSK2647544 RD, DDI in Healthy Young and Elderly Volunteers

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's disease, GSK2647544, drug-drug interaction, healthy subjects, Lp-PLA2, simvastatin Read More

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