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

January 28, 2013
August 28, 2013
March 2013
July 2013   (final data collection date for primary outcome measure)
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.

To assess the effect of multiple dose atorvastatin on the steady state pharmacokinetics of raltegravir and vice versa by intrasubject comparison in healthy subjects. [ 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.

Complete list of historical versions of study NCT01779687 on ClinicalTrials.gov Archive Site
  • 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).
  • To evaluate the safety and tolerability of co-administration of raltegravir and atorvastatin in healthy subjects [ 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.
  • To investigate the non-steady state changes in serum LDL cholesterol secondary to short-term atorvastatin use in the presence or absence of raltegravir [ 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).
Not Provided
Not Provided
 
Pharmacokinetic Drug Interaction Study Between Raltegravir and Atorvastatin.
Pharmacokinetic Drug Interaction Study Between Raltegravir and Atorvastatin (AVIATOR).

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
  • HIV
  • Hypercholesterolaemia
  • 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
  • Active Comparator: raltegravir alone
    Raltegravir 400 mg BID for 7 days
    Intervention: Drug: raltegravir
  • Active Comparator: Atorvastatin alone
    Atorvastatin 20 mg QD for 7 days
    Intervention: Drug: Atorvastatin
  • Experimental: Raltegravir + atorvastatin
    Raltegravir 400 mg BID + Atorvastatin 20 mg QD for 7 days
    Interventions:
    • Drug: raltegravir
    • Drug: Atorvastatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
August 2013
July 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT01779687
UMCNAKF-12.03
No
Radboud University
Radboud University
Merck Sharp & Dohme Corp.
Principal Investigator: David Burger Radboud University
Radboud University
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP