The Influence of Raltegravir on Pravastatin Pharmacokinetics(GRAPPA)

Study Overview
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Brief Summary
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The purpose of this trial is to determine the effect of raltegravir on pravastatin pharmacokinetics and vice versa by intrasubject comparison.

Detailed Description
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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.

Official Title
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The Influence of Raltegravir on Pravastatin Pharmacokinetics in Healthy Volunteers (GRAPPA)

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Pravastatin
* Drug: Raltegravir
* Drug: Pravastatin and raltegravir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Pravastatin 40 mg QD for 4 days | Drug: Pravastatin<br>* 40 mg tablet; QD; 4 days<br>* Other names: Selektine;|
| Active Comparator: B<br>Raltegravir 400mg BD for 4 days | Drug: Raltegravir<br>* 400mg tablet; BD 4 days<br>* Other names: Isentress;|
| Experimental: C<br>Interaction between pravastatin and raltegravir | Drug: Pravastatin and raltegravir<br>* pravastatin 40mg tablet QD for 4 days; raltegravir 400mg tablet BD for 4 days<br>* Other names: Selektine and Isentress;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| To evaluate the safety of combined use of pravastatin and raltegravir |  | entire trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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interaction, statins, pharmacokinetics