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Pharmacokinetic Study of the HCV Protease Inhibitor Bo-cePRevir and the Proton Pump Inhibitor OMeprazOle (PROMO) (PROMO)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01470690
First Posted: November 11, 2011
Last Update Posted: November 27, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Radboud University
  Purpose

The objective of this study is to determine the effect of multiple dose omeprazole on the pharmacokinetics of boceprevir and vice versa.

Furthermore, the safety of steady state boceprevir combined with multiple dose omeprazole will be evaluated.


Condition Intervention Phase
HCV Infections Gastric Acid-related Disorders Drug: boceprevir Drug: Omeprazole Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Official Title: Pharmacokinetic Study of the HCV Protease Inhibitor Bo-cePRevir and the Proton Pump Inhibitor OMeprazOle (PROMO)

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • boceprevir concentrations [ Time Frame: AUC: pre-dose, 0.5, 1. 1.5, 2, 2.5, 3, 4, 5, 6 and 8h ]
    to determine the effect of chronic use of omeprazole on the steady state pharmacokinetics of boceprevir


Secondary Outcome Measures:
  • omeprazole concentrations [ Time Frame: AUC: pre-dose, 0.5, 1. 1.5, 2, 2.5, 3, 4, 5, 6 and 8h ]
    to determine the effect of chronic use of boceprevir on the steady state pharmacokinetics of omeprazole

  • adverse events [ Time Frame: entire study ]
    to determine the safety of combined use of boceprevir and omeprazole


Enrollment: 24
Study Start Date: October 2011
Study Completion Date: January 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: boceprevir
Boceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5 (BOC alone)
Drug: boceprevir
Boceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5
Active Comparator: omeprazole
Omeprazole 40 mg QD for 5 consecutive days (OME alone)
Drug: Omeprazole
Omeprazole 40 mg QD for 5 consecutive days
Experimental: boceprevir+omeprazole
Omeprazole 40 mg QD for 5 consecutive days combined with boceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5 (BOC+OME)
Drug: boceprevir
Boceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5
Drug: Omeprazole
Omeprazole 40 mg QD for 5 consecutive days

Detailed Description:

It is known that some drugs can significantly influence the bioavailability of other drugs. For example the proton pump inhibitors decrease the absorption of some protease inhibitors used in HIV treatment or of some oral tyrosine kinase inhibitors used in oncology. Proton pump inhibitors increase the pH in the stomach and might therefore decrease the solubility of other drugs with decreased absorption as a consequence.

Boceprevir (BOC) is an Hepatitis C (HCV) NS3 serine protease inhibitor that has recently received FDA approval for the treatment of chronic HCV infection. The drug substance is slightly soluble in water and administration with food increases the oral bioavailability of BOC relative to the fasted state, by 40% to 60% based on AUC.

Omeprazole (OME) is the most frequently used proton pump inhibitor. It is the second most prescribed drug in The Netherlands, with 5 million prescriptions a year.

OME is metabolized by CYP2C19 and CYP3A4 and is known to induce CYP1A2 and inhibit CYP2C19. BOC is a potent inhibitor of CYP3A4/5 and is not metabolised by CYP1A2 or CYP2C19. No interaction on metabolism of BOC is expected. However, an increase of OME levels may be expected due to the inhibition of CYP3A4 by BOC.

As proton pump inhibitors are widely used it is relevant to know if a drug-drug interaction between proton pump inhibitors and BOC exists which might influence the bioavailability of BOC.

This study is designed to determine the effect of multiple dose omeprazole on the pharmacokinetics of boceprevir and vice versa.

Furthermore, the safety of steady state boceprevir combined with multiple dose omeprazole will be evaluated.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 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 breastfeeding 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), except 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 dis-orders (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 Day 1.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01470690


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

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01470690     History of Changes
Other Study ID Numbers: UMCN-AKF 10.06
First Submitted: November 1, 2011
First Posted: November 11, 2011
Last Update Posted: November 27, 2012
Last Verified: November 2012

Keywords provided by Radboud University:
HVC infection
gastric acid-related disorders
proton pump inhibitor
interaction
pharmacokinetics
boceprevir
omeprazole

Additional relevant MeSH terms:
Omeprazole
Proton Pump Inhibitors
Protease Inhibitors
HIV Protease Inhibitors
Anti-Ulcer Agents
Gastrointestinal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents