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

NCT01470690 | Completed Phase 1

• 1 other identifier: UMCN-AKF 10.06
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

HCV Infections; Gastric Acid-related Disorders

Keywords

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

Outcome Measures

Primary Outcomes (1)

• boceprevir concentrations

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

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

Secondary Outcomes (2)

• omeprazole concentrations

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

• adverse events

  entire study

Study Arms (3)

boceprevir

ACTIVE COMPARATOR

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

Drug: boceprevir

omeprazole

ACTIVE COMPARATOR

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

Drug: Omeprazole

boceprevir+omeprazole

EXPERIMENTAL

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; Drug: Omeprazole

Interventions

boceprevir DRUG

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

boceprevir; boceprevir+omeprazole

Omeprazole DRUG

Omeprazole 40 mg QD for 5 consecutive days

boceprevir+omeprazole; omeprazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Crcn, Runmc

Nijmegen, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 23429642 RESULT

Related Links

• Link to abstract on AASLD 2012 liver learning website, containing results of the PROMO study.

MeSH Terms

Interventions

N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; Omeprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• David Burger, Prof PharmD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2011
• First Posted: November 11, 2011
• Study Start: October 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: January 1, 2012
• Last Updated: December 1, 2020

Record last verified: 2020-11

Locations

NL (1)