The Influence of Raltegravir on Pravastatin Pharmacokinetics(GRAPPA)

Condition(s) targeted: HIV Infections

Intervention: Pravastatin (Drug); Raltegravir (Drug); Pravastatin and raltegravir (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Radboud University

Official(s) and/or principal investigator(s):
David M Burger, PharmD PhD, Principal Investigator, Affiliation: Radboud University

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

Official title: The Influence of Raltegravir on Pravastatin Pharmacokinetics in Healthy Volunteers (GRAPPA)

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Plasma concentrations of pravastatin and raltegravir.

Secondary outcome:

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

Determination of pharmacokinetic parameters

To evaluate the safety of combined use of pravastatin and raltegravir

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.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

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

Radboud University Nijmegen Medical Centre, Nijmegen, Gelderland, Netherlands

Publication in Journal of Acquired Immune Deficiency Syndromes; Issue: Volume 55(1), 1 September 2010, pp 82-86

Starting date: May 2008
Last updated: June 6, 2011