Pharmacokinetic Drug Interaction Study Between Raltegravir and Atorvastatin. (AVIATOR)
Primary Purpose
HIV, Hypercholesterolaemia
Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
raltegravir
Atorvastatin
Sponsored by
About this trial
This is an interventional other trial for HIV focused on measuring pharmacokinetic, interaction, cholesterol, raltegravir, atorvastatin
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.
Sites / Locations
- CRCN Radboud University Nijmegen Medical Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Experimental
Arm Label
raltegravir alone
Atorvastatin alone
Raltegravir + atorvastatin
Arm Description
Raltegravir 400 mg BID for 7 days
Atorvastatin 20 mg QD for 7 days
Raltegravir 400 mg BID + Atorvastatin 20 mg QD for 7 days
Outcomes
Primary Outcome Measures
raltegravir AUC and atorvastatin AUC
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
Adverse events will be scored during the entire study. Laboratory measurements for safety will be collected frequently during the study.
serum LDL cholesterol
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).
Full Information
NCT ID
NCT01779687
First Posted
January 28, 2013
Last Updated
October 16, 2020
Sponsor
Radboud University Medical Center
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01779687
Brief Title
Pharmacokinetic Drug Interaction Study Between Raltegravir and Atorvastatin.
Acronym
AVIATOR
Official Title
Pharmacokinetic Drug Interaction Study Between Raltegravir and Atorvastatin (AVIATOR).
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV, Hypercholesterolaemia
Keywords
pharmacokinetic, interaction, cholesterol, raltegravir, atorvastatin
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
raltegravir alone
Arm Type
Active Comparator
Arm Description
Raltegravir 400 mg BID for 7 days
Arm Title
Atorvastatin alone
Arm Type
Active Comparator
Arm Description
Atorvastatin 20 mg QD for 7 days
Arm Title
Raltegravir + atorvastatin
Arm Type
Experimental
Arm Description
Raltegravir 400 mg BID + Atorvastatin 20 mg QD for 7 days
Intervention Type
Drug
Intervention Name(s)
raltegravir
Other Intervention Name(s)
raltegravir dosing for 7 days
Intervention Description
Raltegravir 400 mg BID for 7 days
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Intervention Description
Atorvastatin 20 mg QD for 7 days
Primary Outcome Measure Information:
Title
raltegravir AUC and atorvastatin AUC
Description
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.
Time Frame
day 7 of each treatment period
Secondary Outcome Measure Information:
Title
adverse events
Description
Adverse events will be scored during the entire study. Laboratory measurements for safety will be collected frequently during the study.
Time Frame
entire study
Title
serum LDL cholesterol
Description
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).
Time Frame
Day 1 and day 7 of each treatment period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Burger
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
CRCN Radboud University Nijmegen Medical Centre
City
Nijmegen
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
25942458
Citation
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.
Results Reference
result
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/25942458
Description
published results AVIATOR trial
Learn more about this trial
Pharmacokinetic Drug Interaction Study Between Raltegravir and Atorvastatin.
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