Pharmacokinetic Drug Interaction Study Between Raltegravir and Atorvastatin.

NCT01779687 | Completed Phase 1

• 1 other identifier: UMCNAKF-12.03
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Keywords

pharmacokinetic; interaction; cholesterol; raltegravir; atorvastatin

Outcome Measures

Primary Outcomes (1)

• 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.

  day 7 of each treatment period

Secondary Outcomes (2)

• adverse events

  entire study

• serum LDL cholesterol

  Day 1 and day 7 of each treatment period

Study Arms (3)

raltegravir alone

ACTIVE COMPARATOR

Raltegravir 400 mg BID for 7 days

Drug: raltegravir

Atorvastatin alone

ACTIVE COMPARATOR

Atorvastatin 20 mg QD for 7 days

Drug: Atorvastatin

Raltegravir + atorvastatin

EXPERIMENTAL

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

Drug: raltegravir; Drug: Atorvastatin

Interventions

raltegravir DRUG

Raltegravir 400 mg BID for 7 days

Also known as: raltegravir dosing for 7 days

Raltegravir + atorvastatin; raltegravir alone

Atorvastatin DRUG

Atorvastatin 20 mg QD for 7 days

Atorvastatin alone; Raltegravir + atorvastatin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

CRCN Radboud University Nijmegen Medical Centre

Nijmegen, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 25942458 RESULT

Related Links

• published results AVIATOR trial

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

Raltegravir Potassium; Atorvastatin

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• David Burger

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2013
• First Posted: January 30, 2013
• Study Start: March 1, 2013
• Primary Completion: July 1, 2013
• Study Completion: August 1, 2013
• Last Updated: October 20, 2020

Record last verified: 2015-06

Locations

NL (1)