Clinical trial NCT00665717: The Influence of Raltegravir on Pravastatin Pharmacokinetics(GRAPPA)
Official title: The Influence of Raltegravir on Pravastatin Pharmacokinetics in Healthy Volunteers (GRAPPA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: interaction
statins
pharmacokinetics
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2008-04-24
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Plasma concentrations of pravastatin and raltegravir.
timeFrame: 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 outcomes:
measure: 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
timeFrame: Screening and Days 1, 5, 15, 19, 29 and 33.
measure: Determination of pharmacokinetic parameters
timeFrame: at each sampling time
measure: To evaluate the safety of combined use of pravastatin and raltegravir
timeFrame: entire trial
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: David M Burger, PharmD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Luin M, Colbers A, van Ewijk-Beneken Kolmer EW, Verweij-van Wissen CP, Schouwenberg B, Hoitsma A, da Silva HG, Burger DM. Drug-drug interactions between raltegravir and pravastatin in healthy volunteers. J Acquir Immune Defic Syndr. 2010 Sep;55(1):82-6. doi: 10.1097/QAI.0b013e3181d9a354.