Official Title: “The Influence of Raltegravir on Pravastatin Pharmacokinetics in Healthy Volunteers (GRAPPA)”

The purpose of this trial is to determine the effect of raltegravir on pravastatin pharmacokinetics and vice versa by intrasubject comparison.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Crossover Assignment, Pharmacokinetics Study

Study Primary Completion Date: September 2008

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.

Intervention(s) in this Clinical Trial

• Drug: Pravastatin
  • 40 mg tablet; QD; 4 days
• Drug: Raltegravir
  • 400mg tablet; BD 4 days
• Drug: Pravastatin and raltegravir
  • pravastatin 40mg tablet QD for 4 days; raltegravir 400mg tablet BD for 4 days

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: A
  • Pravastatin 40 mg QD for 4 days
• Active Comparator: B
  • Raltegravir 400mg BD for 4 days
• Experimental: C
  • Interaction between pravastatin and raltegravir

Primary Measures

• Plasma concentrations of pravastatin and raltegravir.
  • Time Frame: 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.
    Safety Issue?: No

Secondary Measures

• 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
  • Time Frame: Screening and Days 1, 5, 15, 19, 29 and 33.
    Safety Issue?: Yes
• Determination of pharmacokinetic parameters
  • Time Frame: at each sampling time
    Safety Issue?: No
• To evaluate the safety of combined use of pravastatin and raltegravir
  • Time Frame: entire trial
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Radboud University

Overall Clinical Trial Officials and Contacts

David M Burger, PharmD PhD Principal Investigator Radboud University  

Overall Contact: David M Burger, PharmD PhD ++31243616405 d.burger@akf.umcn.nl

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00665717

Study ID Number: UMCN-AKF 07.05

ClinicalTrials.gov Identifier: NCT00665717

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)