Pharmacokinetic Study of the HCV Protease Inhibitor Boceprevir and the HIV Integrase Inhibitor Raltegravir
Information source: Radboud University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; HCV Infections
Intervention: boceprevir (Drug); raltegravir (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Radboud University Official(s) and/or principal investigator(s): David Burger, PharmD, PhD, Principal Investigator, Affiliation: Radboud University
Summary
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.
Clinical Details
Official title: Pharmacokinetic Study of the HCV Protease Inhibitor Boceprevir and the HIV Integrase Inhibitor Raltegravir
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: raltegravir concentrations
Secondary outcome: adverse eventsboceprevir concentrations
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
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
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.
Locations and Contacts
CRCN, Nijmegen, Netherlands
Additional Information
abstract with results of the study, presented at CROI 2012
Starting date: August 2011
Last updated: July 23, 2012
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