Pharmacokinetic Drug Interaction Study Between Raltegravir and Atorvastatin.

NCT ID: NCT01779687

Last Updated: 2020-10-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2013-08-31

Brief Summary

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.

Conditions

HIV; Hypercholesterolaemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

raltegravir alone

Raltegravir 400 mg BID for 7 days

Group Type: ACTIVE_COMPARATOR

raltegravir

Intervention Type: DRUG

Raltegravir 400 mg BID for 7 days

Atorvastatin alone

Atorvastatin 20 mg QD for 7 days

Group Type: ACTIVE_COMPARATOR

Atorvastatin

Intervention Type: DRUG

Atorvastatin 20 mg QD for 7 days

Raltegravir + atorvastatin

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

Group Type: EXPERIMENTAL

raltegravir

Intervention Type: DRUG

Raltegravir 400 mg BID for 7 days

Atorvastatin

Intervention Type: DRUG

Atorvastatin 20 mg QD for 7 days

Interventions

raltegravir

Raltegravir 400 mg BID for 7 days

Intervention Type: DRUG

Atorvastatin

Atorvastatin 20 mg QD for 7 days

Intervention Type: DRUG

Other Intervention Names

raltegravir dosing for 7 days

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Burger

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

CRCN Radboud University Nijmegen Medical Centre

Nijmegen, , Netherlands

Countries

Netherlands

References

Blonk M, van Beek M, Colbers A, Schouwenberg B, Burger D. Pharmacokinetic Drug-Drug Interaction Study Between Raltegravir and Atorvastatin 20 mg in Healthy Volunteers. J Acquir Immune Defic Syndr. 2015 May 1;69(1):44-51. doi: 10.1097/QAI.0000000000000544.

Reference Type: RESULT

PMID: 25942458 (View on PubMed)

Related Links

http://www.ncbi.nlm.nih.gov/pubmed/25942458

published results AVIATOR trial

Other Identifiers

UMCNAKF-12.03

Identifier Type: -

Identifier Source: org_study_id