Comparison of Concentration-time Course of Plasma and Intracellular Raltegravir in Healthy Volunteers

• Status: Completed
• Trial end date: 2010-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The investigators hypothesize that the concentration-time profile of raltegravir is different in cells than that in plasma. Intracellular raltegravir concentrations may be higher and its half-life longer than in plasma. This may explain the efficacy of raltegravir despite variable plasma concentrations.

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

Details

• Lead Sponsor: Changi General Hospital
• Collaborators: Merck Sharp & Dohme Corp.; National University Hospital, Singapore
• Treatments: Raltegravir Potassium

Criteria

Inclusion Criteria:

• Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2 and weigh at least 50kg.

• Non-smoking or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 3 months prior to selection.

• Women of childbearing potential (WOCBP) must not be nursing or pregnant.

• Women of childbearing potential (have not been postmenopausal for at least 2 years nor undergone total hysterectomy) must have a negative serum Beta-HCG test performed at screening.

• Female subjects who are not of reproductive potential (have been postmenopausal for at least 2 years or undergone total hysterectomy) or whose male partner has undergone successful vasectomy with resultant azoospermia or has azoospermia for any other reason, are eligible without requiring the use of contraception. Documentation of menopause, sterilization (total hysterectomy or vasectomy) and azoospermia must be provided to study personnel at time of screening.

• Both male and female study volunteers of reproductive potential must agree not to participate in a conception process (i.e., active attempt to become pregnant or to impregnate via sperm donation or in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female study volunteer/male partner must use a form of contraception as specified below while receiving protocol-specified medication(s) and for 7 days after stopping the medication(s). Male study volunteers will be required to use a barrier method for at least 7 days after completion of the study.

Exclusion Criteria:

• History or current evidence of any significant acute or chronic medical illness that, within the investigator's discretion, would interfere with the conduct or interpretation of the study.

• Proven or suspected acute hepatitis at the time of study entry.

• Current or recent (within 3 months) gastrointestinal disease which would interfere with the conduct or interpretation of the study.

• Any major surgery within 8 weeks of enrollment. Any gastrointestinal surgery that could impact upon the absorption of study drug.

• Donation of blood or plasma within 60 days of screening.

• Inability to tolerate oral medication.

• Inability to tolerate venepuncture and/or absence of secure venous access.

• Inability to give informed consent voluntarily before the first trial-related activity.

• Known or suspected HIV infection or chronic HBV or HCV infection

• Known active drug or alcohol abuse, which in the opinion of the investigator makes study participation to completion unlikely.

• Any other significant medical, psychiatric and/or social issue as determined by the Investigator that would compromise subject's safety and/or compliance with trial procedures.

• Subjects with AST, ALT or total bilirubin above the upper limit of normal.

• Haemoglobin < 10.9 g/dL, and platelet count < 125,000/mm3.

• Creatinine clearance <60 ml/min

• Lipase or pancreatic amylase >1.1x ULN

• Fasting triglyceride >300 mg/dL.

• Absolute Neutrophil Count (ANC) <1300/mm3

• Serum creatinine grade 1 or greater (≥ 1.1 x upper limit of laboratory normal range [ULN])

• Any other clinically significant screening lab abnormality (as determined by the investigator)

• Exposure to any investigational drug (excluding raltegravir) within 90 days of enrollment and throughout the study.

• Any previous clinically significant allergy or hypersensitivity or intolerance to raltegravir or any other ingredient of the tablets.

• Use of any agent, within 2 weeks of dosing, that is known to induce or inhibit drug metabolizing enzymes.

• Use of concomitant medication, including investigational, prescription, and any over-the-counter drugs and dietary supplements with the following exceptions, aspirin, acetaminophen, chlorpheniramine, daily multivitamins, mineral supplements and hormonal oral contraceptives. Concomitant medication other than those listed above must have been discontinued within 14 days of study entry.