Pharmacokinetic Study of the HCV Protease Inhibitor Boceprevir and the HIV Integrase Inhibitor Raltegravir (OPAL)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01288417
First received: January 26, 2011
Last updated: July 23, 2012
Last verified: July 2012
  Purpose

The objective of this study is to evaluate the effect of boceprevir (steady state) on the pharmacokinetics of a single dose of raltegravir. The effect on the boceprevir pharmacokinetics of a single dose raltegravir will also be evaluated (compared to historical controls). Furthermore, the safety profile of the combination is studied.


Condition Intervention Phase
HIV Infections
HCV Infections
Drug: boceprevir
Drug: raltegravir
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetic Study of the HCV Protease Inhibitor Boceprevir and the HIV Integrase Inhibitor Raltegravir

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • raltegravir concentrations [ Time Frame: during 12hours on two occasions ] [ Designated as safety issue: No ]
    To determine the effect of chronic use of boceprevir on the single-dose pharmacokinetics of raltegravir 400mg in healthy volunteers


Secondary Outcome Measures:
  • adverse events [ Time Frame: entire study ] [ Designated as safety issue: Yes ]
    to determine the safety of a single dose of raltegravir 400mg when combined with chronic use of boceprevir

  • boceprevir concentrations [ Time Frame: during 8 hours on one occasion; predose 4 times over a period of 10 days ] [ Designated as safety issue: No ]
    To determine the effect of a single-dose pharmacokinetics of raltegravir 400mg on chronic use of boceprevir in healthy volunteers


Enrollment: 24
Study Start Date: August 2011
Study Completion Date: December 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: boceprevir + raltegravir
9 days of boceprevir 800mg TID; day 10 two doses of boceprevir 800mg and one dose of raltegravir 400mg
Drug: boceprevir
10 days of boceprevir 800mg TID
Drug: raltegravir
raltegravir 400mg single dose
Other Name: Isentress
Active Comparator: raltegravir alone
single dose of raltegravir 400mg
Drug: raltegravir
raltegravir 400mg single dose
Other Name: Isentress

Detailed Description:

A considerable percentage of HIV infected patients is also infected with the hepatitis C virus (HCV). HIV/HCV co-infected patients are likely to simultaneously use treatment for their HIV infection as well as HCV treatment. Therefore, it is important to know if drug-drug interactions occur when combining those treatments.

Raltegravir is an HIV integrase inhibitor and approved by the FDA in 2007. Boceprevir is a potent HCV NS3 serine protease inhibitor and is currently in Phase III clinical development.

Combined use of boceprevir and raltegravir is not expected to give a major drug-drug interaction as raltegravir is not a CYP3A substrate and thus will not be affected by the strong inhibition of CYP3A by boceprevir. Raltegravir is metabolized by UGT but boceprevir is not known to influence UGT. However, recent data indicate that raltegravir is a P-gp substrate and boceprevir is a substrate and a moderate inhibitor of P-gp in vitro.

Even when no drug interaction is expected, it may be recommended to collect sufficient evidence that this is the case as in many cases un-expected drug-drug interactions have been observed in the past.

The current study is designed to evaluate the effect of steady state boceprevir on the pharmacokinetics of a single dose of raltegravir and the safety profile when used in combination. Furthermore the effect of a single dose raltegravir is studied on the pharmacokinetics of steady state boceprevir in comparison with historical controls.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subject is at least 18 and not older than 55 years at scree-ning.
  • 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 Day 1. 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 trial.
  • Therapy with any drug (for two weeks preceding dosing), ex-cept for paracetamol.
  • 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.
  • 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 trial and the procedures required.
  • Participation in a drug trial 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01288417

Locations
Netherlands
CRCN
Nijmegen, Netherlands
Sponsors and Collaborators
Radboud University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: David Burger, PharmD, PhD Radboud University
  More Information

Additional Information:
No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01288417     History of Changes
Other Study ID Numbers: UMCN-AKF 10.05
Study First Received: January 26, 2011
Last Updated: July 23, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
HIV infections
HCV infections
interaction
pharmacokinetics
raltegravir
boceprevir

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Protease Inhibitors
HIV Protease Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 14, 2014