The Influence of Raltegravir on Pravastatin Pharmacokinetics(GRAPPA) - Full Text View

Sponsors and Collaborators:	Radboud University Merck
Information provided by:	Radboud University
ClinicalTrials.gov Identifier:	NCT00665717

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 I

MedlinePlus related topics: AIDS

Drug Information available for: Pravastatin Pravastatin sodium Raltegravir

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Crossover Assignment, Pharmacokinetics Study
Official Title:	The Influence of Raltegravir on Pravastatin Pharmacokinetics in Healthy Volunteers (GRAPPA)

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 ]

Estimated 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
A: Active Comparator Pravastatin 40 mg QD for 4 days	Drug: Pravastatin 40 mg tablet; QD; 4 days
B: Active Comparator Raltegravir 400mg BD for 4 days	Drug: Raltegravir 400mg tablet; BD 4 days
C: Experimental Interaction between pravastatin and raltegravir	Drug: Pravastatin and raltegravir pravastatin 40mg tablet QD for 4 days; raltegravir 400mg tablet BD for 4 days

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, Gelderland
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands

Sponsors and Collaborators

Radboud University

Merck

Investigators

Principal Investigator:

David M Burger, PharmD PhD

Radboud University

More Information

No publications provided

Responsible Party:	Radboud University Nijmegen Medical Centre ( Dr. D.M. Burger, hospital pharmacist )
Study ID Numbers:	UMCN-AKF 07.05
Study First Received:	April 23, 2008
Last Updated:	October 21, 2008
ClinicalTrials.gov Identifier:	NCT00665717
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:

interaction
statins
pharmacokinetics

Study placed in the following topic categories:

Virus Diseases
Pravastatin
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome
Healthy
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Antimetabolites
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Antilipemic Agents
Enzyme Inhibitors

Anticholesteremic Agents
Infection
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Therapeutic Uses
Lentivirus Infections

ClinicalTrials.gov processed this record on February 12, 2009