Pharmacokinetic Drug Interaction Study Between Raltegravir and Atorvastatin. - Full Text View

Purpose

Dyslipidemia is highly prevalent among patients with HIV infection and contributes to the increased cardiovascular disease risk in this patient population. Atorvastatin lowers plasma low-density lipoprotein (LDL) cholesterol levels and is used for prevention of artherosclerotic disease. Raltegravir, an HIV integrase inhibitor, could be one of the preferred antiretroviral agents in HIV patients with dyslipidemia because it has a beneficial lipid profile.

Theoretically, no clinically relevant drug interaction is expected between atorvastatin and raltegravir. However, atorvastatin and raltegravir share similar metabolic pathways which could be relevant in the occurrence of pharmacokinetic interactions. In order to be able to recommend raltegravir and atorvastatin concomitant use, a pharmacokinetic study in healthy volunteers is proposed.

Condition	Intervention	Phase
HIV Hypercholesterolaemia	Drug: raltegravir Drug: Atorvastatin	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label
Official Title:	Pharmacokinetic Drug Interaction Study Between Raltegravir and Atorvastatin (AVIATOR).

Resource links provided by NLM:

MedlinePlus related topics: Cholesterol Drug Reactions HIV/AIDS

Drug Information available for: Atorvastatin Atorvastatin calcium Raltegravir Raltegravir potassium

Genetic and Rare Diseases Information Center resources: Sphingolipidosis

U.S. FDA Resources

Further study details as provided by Radboud University:

Primary Outcome Measures:

raltegravir AUC and atorvastatin AUC [ Time Frame: day 7 of each treatment period ] [ Designated as safety issue: No ]
The comparison of steady state raltegravir (400 mg BID for 7 days) pharmacokinetics (AUC0-12h, Cmax, C12h) with atorvastatin (20 mg QD for 7 days) vs. raltegravir alone by intrasubject comparison.

The comparison of steady state atorvastatin (20 mg QD for 7 days) pharmacokinetics (AUC0-24h, Cmax, C24h) with raltegravir (400 mg BID for 7 days) vs. atorvastatin alone by intrasubject comparison.

Secondary Outcome Measures:

adverse events [ Time Frame: entire study ] [ Designated as safety issue: Yes ]
Adverse events will be scored during the entire study. Laboratory measurements for safety will be collected frequently during the study.
serum LDL cholesterol [ Time Frame: Day 1 and day 7 of each treatment period ] [ Designated as safety issue: No ]
12-hour-fasting serum lipid profile (total cholesterol, triglycerides, HDL cholesterol, non-HDL cholesterol, LDL cholesterol) at screening and on the first day and the last day of each treatment period (Days 1, 7, 22, 28, 43 and 49).


Enrollment:	24
Study Start Date:	March 2013
Study Completion Date:	August 2013
Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: raltegravir alone Raltegravir 400 mg BID for 7 days	Drug: raltegravir Raltegravir 400 mg BID for 7 days Other Name: raltegravir dosing for 7 days
Active Comparator: Atorvastatin alone Atorvastatin 20 mg QD for 7 days	Drug: Atorvastatin Atorvastatin 20 mg QD for 7 days Other Name: Atorvastatin
Experimental: Raltegravir + atorvastatin Raltegravir 400 mg BID + Atorvastatin 20 mg QD for 7 days	Drug: raltegravir Raltegravir 400 mg BID for 7 days Other Name: raltegravir dosing for 7 days Drug: Atorvastatin Atorvastatin 20 mg QD for 7 days Other Name: Atorvastatin

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 at screening.
Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to the first dosing
Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry, haematology and urinalysis testing within 4 weeks prior to the first dose. Results of biochemistry, haematology and urinalysis testing should be within the laboratory's reference ranges. If laboratory results are not within the reference ranges, the subject is included on condition that the Investigator judges that the deviations are not clinically relevant. This should be clearly recorded.
Subject has a normal blood pressure and pulse rate, according to the Investigator's judgement.

Exclusion Criteria:

Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
Positive HIV test.
Positive hepatitis B or C test.
Pregnant female (as confirmed by an hCG test performed less than 4 weeks before day 1) or breast-feeding female. Female subjects of childbearing potential without adequate contraception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout the entire conduct of the study.
Therapy with any drug (for two weeks preceding dosing), except for acetaminophen.
Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), psychiatric disorders, gastro-intestinal disorders, renal and hepatic disorders, hormonal disorders (especially diabetes mellitus), coagulation disorders, musculoskeletal and connective tissue disorders.
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 study and the procedures required.
Participation in a drug study 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01779687

Locations


Netherlands
CRCN Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands

Sponsors and Collaborators

Radboud University

Merck Sharp & Dohme Corp.

Investigators


Principal Investigator:	David Burger	Radboud University

More Information

No publications provided


Responsible Party:	Radboud University
ClinicalTrials.gov Identifier:	NCT01779687 History of Changes
Other Study ID Numbers:	UMCNAKF-12.03
Study First Received:	January 28, 2013
Last Updated:	August 28, 2013
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:


pharmacokinetic interaction cholesterol raltegravir atorvastatin

Additional relevant MeSH terms:


Hypercholesterolemia Dyslipidemias Hyperlipidemias Lipid Metabolism Disorders Metabolic Diseases Atorvastatin Anticholesteremic Agents Antimetabolites	Enzyme Inhibitors Hydroxymethylglutaryl-CoA Reductase Inhibitors Hypolipidemic Agents Lipid Regulating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015

Pharmacokinetic Drug Interaction Study Between Raltegravir and Atorvastatin. (AVIATOR)