The Influence of Raltegravir on Pravastatin Pharmacokinetics(GRAPPA)

Phase 1

Completed

• Conditions: HIV Infections
• Interventions: Drug: Pravastatin and raltegravir; Drug: Pravastatin; Drug: Raltegravir

• Registration Number: NCT00665717
• Lead Sponsor: Radboud University Medical Center

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.

Study Timeline

• Study First Submitted: 2008-04-23
• Study First Submitted QC: 2008-04-23
• Study First Posted: 2008-04-24
• Study Start: 2008-05
• Primary Completion: 2008-09
• Study Completion: 2008-10
• Status Verified: 2011-05
• Last Update Submitted: 2020-10-16
• Last Update Posted: 2020-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
C	Pravastatin and raltegravir	Interaction between pravastatin and raltegravir
A	Pravastatin	Pravastatin 40 mg QD for 4 days
B	Raltegravir	Raltegravir 400mg BD for 4 days

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
To evaluate the safety of combined use of pravastatin and raltegravir	entire trial
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

Trial Locations

Locations (1)

Radboud University Nijmegen Medical Centre; 🇳🇱 Nijmegen, Gelderland, Netherlands