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

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01779687
First received: January 28, 2013
Last updated: August 28, 2013
Last verified: August 2013
  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:


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

ClinicalTrials.gov processed this record on July 24, 2014