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

Primary Purpose

HCV Infections, Gastric Acid-related Disorders

Status

Completed

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

boceprevir

Omeprazole

About this trial

This is an interventional other trial for HCV Infections focused on measuring HVC infection, gastric acid-related disorders, proton pump inhibitor, interaction, pharmacokinetics, boceprevir, omeprazole

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Crcn, Runmc

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

boceprevir

omeprazole

boceprevir+omeprazole

Arm Description

Boceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5 (BOC alone)

Omeprazole 40 mg QD for 5 consecutive days (OME alone)

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)

Outcomes

Primary Outcome Measures

boceprevir concentrations

to determine the effect of chronic use of omeprazole on the steady state pharmacokinetics of boceprevir

Secondary Outcome Measures

omeprazole concentrations

to determine the effect of chronic use of boceprevir on the steady state pharmacokinetics of omeprazole

adverse events

to determine the safety of combined use of boceprevir and omeprazole

Full Information

NCT ID

NCT01470690

First Posted

November 1, 2011

Last Updated

November 26, 2020

Sponsor

Radboud University Medical Center

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01470690

Brief Title

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

Acronym

PROMO

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Completed

Study Start Date

October 2011 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Radboud University Medical Center

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HCV Infections, Gastric Acid-related Disorders

Keywords

HVC infection, gastric acid-related disorders, proton pump inhibitor, interaction, pharmacokinetics, boceprevir, omeprazole

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

boceprevir

Arm Type

Active Comparator

Arm Description

Boceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5 (BOC alone)

Arm Title

omeprazole

Arm Type

Active Comparator

Arm Description

Omeprazole 40 mg QD for 5 consecutive days (OME alone)

Arm Title

boceprevir+omeprazole

Arm Type

Experimental

Arm Description

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)

Intervention Type

Drug

Intervention Name(s)

boceprevir

Intervention Description

Boceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5

Intervention Type

Drug

Intervention Name(s)

Omeprazole

Intervention Description

Omeprazole 40 mg QD for 5 consecutive days

Primary Outcome Measure Information:

Title

boceprevir concentrations

Description

to determine the effect of chronic use of omeprazole on the steady state pharmacokinetics of boceprevir

Time Frame

AUC: pre-dose, 0.5, 1. 1.5, 2, 2.5, 3, 4, 5, 6 and 8h

Secondary Outcome Measure Information:

Title

omeprazole concentrations

Description

to determine the effect of chronic use of boceprevir on the steady state pharmacokinetics of omeprazole

Time Frame

AUC: pre-dose, 0.5, 1. 1.5, 2, 2.5, 3, 4, 5, 6 and 8h

Title

adverse events

Description

to determine the safety of combined use of boceprevir and omeprazole

Time Frame

entire study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Burger, Prof PharmD

Organizational Affiliation

Radboud University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Crcn, Runmc

City

Nijmegen

Country

Netherlands

12. IPD Sharing Statement

Citations:

PubMed Identifier

23429642

Citation

de Kanter CT, Colbers AP, Blonk MI, Verweij-van Wissen CP, Schouwenberg BJ, Drenth JP, Burger DM. Lack of a clinically significant drug-drug interaction in healthy volunteers between the HCV protease inhibitor boceprevir and the proton pump inhibitor omeprazole. J Antimicrob Chemother. 2013 Jun;68(6):1415-22. doi: 10.1093/jac/dkt032. Epub 2013 Feb 20.

Results Reference

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

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