The Influence of Raltegravir on Pravastatin Pharmacokinetics(GRAPPA)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00665717
First received: April 23, 2008
Last updated: June 6, 2011
Last verified: May 2011
  Purpose

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00665717

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

Additional Information:
No publications provided

Responsible Party: Dr. D.M. Burger, hospital pharmacist, Radboud University Nijmegen Medical Centre
ClinicalTrials.gov 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:
interaction
statins
pharmacokinetics

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Pravastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014