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

Radboud University Medical Center

Status and phase: Completed; Phase 1

Conditions: HIV; Hypercholesterolaemia

Treatments: Drug: raltegravir; Drug: Atorvastatin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01779687

UMCNAKF-12.03

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

raltegravir alone

Active Comparator group

Description:

Raltegravir 400 mg BID for 7 days

Treatment:

Drug: raltegravir

Atorvastatin alone

Active Comparator group

Description:

Atorvastatin 20 mg QD for 7 days

Treatment:

Drug: Atorvastatin

Raltegravir + atorvastatin

Experimental group

Description:

Raltegravir 400 mg BID + Atorvastatin 20 mg QD for 7 days

Treatment:

Drug: raltegravir

Drug: Atorvastatin