HIV Infections
Conditions
Keywords
interaction, statins, pharmacokinetics
Brief summary
The purpose of this trial is to determine the effect of raltegravir on pravastatin pharmacokinetics and vice versa by intrasubject comparison.
Detailed description
Pravastatin is a first choice statin for HIV-infected patients. Therefore, raltegravir and pravastatin are expected to be co-administered frequently in HIV-infected patients.Since both agents share the same metabolic pathway, there is a potential for a pharmacokinetic drug-drug interaction. Because co-administration will be indicated in many HIV-infected patients, it is essential to investigate this potential interaction.
Interventions
DRUGPravastatin
40 mg tablet; QD; 4 days
DRUGRaltegravir
400mg tablet; BD 4 days
DRUGPravastatin and raltegravir
pravastatin 40mg tablet QD for 4 days; raltegravir 400mg tablet BD for 4 days
Sponsors
Merck Sharp & Dohme LLC
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is at least 18 and not older than 55 years of age. * Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day. * Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2. * Subject is able and willing to sign the Informed Consent Form prior to screening evaluations. * Subject is in good age-appropriate health condition. * Subject has a normal blood pressure and pulse rate.
Exclusion criteria
* Documented history of sensitivity/idiosyncrasy to medicinal products or exci-pients. * Positive HIV test. * Positive hepatitis B or C test. * Pregnant female or breast-feeding female. * Therapy with any drug. * Relevant history or presence of pulmonary disorders (especially COPD), car-diovascular disorders, neurological disorders (especially seizures and mi-graine), gastro-intestinal disorders, renal and hepatic disorders, hormonal disorders (especially diabetes mellitus), coagulation disorders. * Fasting triglyceride levels \> 8.0 mmol/L * Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion. * History of or current abuse of drugs, alcohol or solvents. * Inability to understand the nature and extent of the trial and the procedures required. * Participation in a drug trial within 60 days prior to the first dose. * Donation of blood within 60 days prior to the first dose. * Febrile illness within 3 days before the first dose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma concentrations of pravastatin and raltegravir. | t=0 (predose), 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and (24: for pravastatin only) hours post ingestion on Days 4, 18 and 32. Trough level on Day 2, 16 and 30. |
Secondary
| Measure | Time frame |
|---|---|
| To investigate the non-steady state changes in serum low density lipoprotein (LDL) cholesterol secondary to pravastatin use in the presence or absence of raltegravir | Screening and Days 1, 5, 15, 19, 29 and 33. |
| Determination of pharmacokinetic parameters | at each sampling time |
| To evaluate the safety of combined use of pravastatin and raltegravir | entire trial |
Countries
Netherlands
Outcome results
None listed