HCV InfectionsPhase 1PROMONCT01470690
Pharmacokinetic Study of the HCV Protease Inhibitor Bo-cePRevir and the Proton Pump Inhibitor OMeprazOle (PROMO)
A Phase 1 study testing boceprevir and Omeprazole in people with HCV Infections and Gastric Acid-related Disorders, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- HCV Infections, Gastric Acid-related Disorders
- What is being tested?
- boceprevir and Omeprazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2011to Jan 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- HCV Infections, Gastric Acid-related Disorders
- Being tested
- boceprevir, Omeprazole
- Keywords
- HVC infection, gastric acid-related disorders, proton pump inhibitor, interaction, pharmacokinetics, boceprevir, omeprazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
boceprevirDrug
Boceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5
OmeprazoleDrug
Omeprazole 40 mg QD for 5 consecutive days
| Study group | Role | What they receive |
|---|---|---|
| boceprevir | Active comparator | Boceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5 (BOC alone) Receives: Drug: boceprevir |
| omeprazole | Active comparator | Omeprazole 40 mg QD for 5 consecutive days (OME alone) Receives: 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) Receives: Drug: boceprevir; Drug: Omeprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
boceprevir concentrations
to determine the effect of chronic use of omeprazole on the steady state pharmacokinetics of boceprevir
Measured: AUC: pre-dose, 0.5, 1. 1.5, 2, 2.5, 3, 4, 5, 6 and 8h
Secondary outcomes (2)
omeprazole concentrations
to determine the effect of chronic use of boceprevir on the steady state pharmacokinetics of omeprazole
Measured: AUC: pre-dose, 0.5, 1. 1.5, 2, 2.5, 3, 4, 5, 6 and 8h
adverse events
to determine the safety of combined use of boceprevir and omeprazole
Measured: entire study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2011 (estimated)
- Study startOct 2011
- Primary completionDec 2011
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HCV InfectionsStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- David Burger, Prof PharmD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01470690
- Sponsor's protocol ID
- UMCN-AKF 10.06
- Acronym
- PROMO
- Status last verified
- Nov 2020
- First submitted
- 1 Nov 2011
- Last updated
- 1 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23429642
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Study of the HCV Protease Inhibitor Bo-cePRevir and the Proton Pump Inhibitor OMeprazOle (PROMO)
- ClinicalTrials.gov ID
- NCT01470690
- Acronym / sponsor ID
- PROMO / UMCN-AKF 10.06
- Conditions
- HCV Infections, Gastric Acid-related Disorders
- Keywords
- HVC infection, gastric acid-related disorders, proton pump inhibitor, interaction, pharmacokinetics, boceprevir, omeprazole
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Oct 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 11 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| boceprevir | Active comparator | Drug: boceprevirBoceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5 (BOC alone) |
| omeprazole | Active comparator | Drug: OmeprazoleOmeprazole 40 mg QD for 5 consecutive days (OME alone) |
| boceprevir+omeprazole | Experimental | Drug: boceprevir, Drug: OmeprazoleOmeprazole 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) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| boceprevirBoceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5 | Drug | boceprevir, boceprevir+omeprazole |
| OmeprazoleOmeprazole 40 mg QD for 5 consecutive days | Drug | boceprevir+omeprazole, omeprazole |
Primary outcome
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
2 secondary outcomes
omeprazole concentrations
Time frame: AUC: pre-dose, 0.5, 1. 1.5, 2, 2.5, 3, 4, 5, 6 and 8h
adverse events
Time frame: entire study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2020.
- Results publication: PubMed 23429642de 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.
- Link to abstract on AASLD 2012 liver learning website, containing results of the PROMO study.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Burger, Prof PharmD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing boceprevir and Omeprazole in people with HCV Infections and Gastric Acid-related Disorders, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
boceprevir concentrations (time frame: AUC: pre-dose, 0.5, 1. 1.5, 2, 2.5, 3, 4, 5, 6 and 8h). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01470690, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2020.