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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

January 26, 2011
July 23, 2012
August 2011
November 2011   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01288417 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Pharmacokinetic Study of the HCV Protease Inhibitor Boceprevir and the HIV Integrase Inhibitor Raltegravir
Pharmacokinetic Study of the HCV Protease Inhibitor Boceprevir and the HIV Integrase Inhibitor Raltegravir

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infections
  • HCV Infections
  • Drug: boceprevir
    10 days of boceprevir 800mg TID
  • Drug: raltegravir
    raltegravir 400mg single dose
    Other Name: Isentress
  • Experimental: boceprevir + raltegravir
    9 days of boceprevir 800mg TID; day 10 two doses of boceprevir 800mg and one dose of raltegravir 400mg
    Interventions:
    • Drug: boceprevir
    • Drug: raltegravir
  • Active Comparator: raltegravir alone
    single dose of raltegravir 400mg
    Intervention: Drug: raltegravir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
December 2011
November 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT01288417
UMCN-AKF 10.05
No
Radboud University
Radboud University
Merck Sharp & Dohme Corp.
Principal Investigator: David Burger, PharmD, PhD Radboud University
Radboud University
July 2012

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