The Influence of Raltegravir on Pravastatin Pharmacokinetics(GRAPPA) (GRAPPA)

This study has been completed.
Merck Sharp & Dohme Corp.
Information provided by:
Radboud University Identifier:
First received: April 23, 2008
Last updated: June 6, 2011
Last verified: May 2011
The purpose of this trial is to determine the effect of raltegravir on pravastatin pharmacokinetics and vice versa by intrasubject comparison.

Condition Intervention Phase
HIV Infections
Drug: Pravastatin
Drug: Raltegravir
Drug: Pravastatin and raltegravir
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Influence of Raltegravir on Pravastatin Pharmacokinetics in Healthy Volunteers (GRAPPA)

Resource links provided by NLM:

Further study details as provided by Radboud University:

Primary Outcome 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. ] [ Designated as safety issue: No ]

Secondary Outcome 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. ] [ Designated as safety issue: Yes ]
  • Determination of pharmacokinetic parameters [ Time Frame: at each sampling time ] [ Designated as safety issue: No ]
  • To evaluate the safety of combined use of pravastatin and raltegravir [ Time Frame: entire trial ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: May 2008
Study Completion Date: October 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Pravastatin 40 mg QD for 4 days
Drug: Pravastatin
40 mg tablet; QD; 4 days
Other Name: Selektine
Active Comparator: B
Raltegravir 400mg BD for 4 days
Drug: Raltegravir
400mg tablet; BD 4 days
Other Name: Isentress
Experimental: C
Interaction between pravastatin and raltegravir
Drug: Pravastatin and raltegravir
pravastatin 40mg tablet QD for 4 days; raltegravir 400mg tablet BD for 4 days
Other Name: Selektine and Isentress

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.


Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts 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
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Please refer to this study by its identifier: NCT00665717

Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands
Sponsors and Collaborators
Radboud University
Merck Sharp & Dohme Corp.
Principal Investigator: David M Burger, PharmD PhD Radboud University
  More Information

Additional Information:
Responsible Party: Dr. D.M. Burger, hospital pharmacist, Radboud University Nijmegen Medical Centre Identifier: NCT00665717     History of Changes
Other Study ID Numbers: UMCN-AKF 07.05 
Study First Received: April 23, 2008
Last Updated: June 6, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:

Additional relevant MeSH terms:
Raltegravir Potassium
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Anticholesteremic Agents
Antiviral Agents
Enzyme Inhibitors
HIV Integrase Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Integrase Inhibitors
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action processed this record on May 26, 2016