Primary objectiveTo determine the effect of multiple dose OME on the pharmacokinetics (AUC0-8h, Cmax, C8h) of BOC.Secondary objectives:To determine the effect of steady state BOC on the pharmacokinetics (AUC0-8h, Cmax, C8h) of multiple dose OME.To…
ID
Source
Brief title
Condition
- Gastrointestinal conditions NEC
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the effect of multiple dose OME on the pharmacokinetics (AUC0-8h,
Cmax, C8h) of BOC.
Secondary outcome
To determine the effect of steady state BOC on the pharmacokinetics (AUC0-8h,
Cmax, C8h) of multiple dose OME.
To study the safety of steady state BOC combined with multiple dose OME.
Background summary
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 there-fore decrease the solubility of other drugs with
decreased absorption as a consequence.
Boceprevir (BOC) is an 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.
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.
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 me-tabolism of BOC is expected.
However, an increase of OME levels may be expected due to the inhibition of
CYP3A4 by BOC.
Study objective
Primary objective
To determine the effect of multiple dose OME on the pharmacokinetics (AUC0-8h,
Cmax, C8h) of BOC.
Secondary objectives:
To determine the effect of steady state BOC on the pharmacokinetics (AUC0-8h,
Cmax, C8h) of multiple dose OME.
To study the safety of steady state BOC combined with multiple dose OME.
Study design
Open-label, 3-period, randomized, cross-over, single-centre, phase-I trial
A total of 24 subjects will be enrolled. The 24 subjects will be divided into 6
treatment groups (1 to 6) of 4 subjects.
Each group will take the following medications, but in a different order:
A. OME 40 mg QD for 5 consecutive days (OME alone)
B. BOC 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5
(BOC alone)
C. OME 40 mg QD for 5 consecutive days combined with BOC 800 mg TID for 4
consecutive days + a single dose of 800 mg on Day 5 (BOC+OME)
Washout periods of at least 9 days will be scheduled between treatments.
The treatment group will be assigned at random.
PK days will be on Day 5, 19 and 33.
Intervention
A. OME 40 mg QD for 5 consecutive days (OME alone)
B. BOC 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5
(BOC alone)
C. OME 40 mg QD for 5 consecutive days combined with BOC 800 mg TID for 4
consecutive days + a single dose of 800 mg on Day 5 (BOC+OME)
All subjects get every treatment with a washout periods of at least 9 days
between treatments.
Study burden and risks
The study participants are healthy volunteers and will not benefit from the
participation in this clinical trial.
They will visit the centre for short visits (1 hour) 9 times and stay for appr.
10 hours on three occasions. The duration of the entire trial (excluding
screening period) is 33 days.
For pharmacokinetic purposes, in total 39 times a blood sample will be taken;
the total volume taken will be maximally appr. 350mL.
During the days that blood samples will be collected for a pharma-cokinetic
curve an intravenous cannula will be inserted to facilitate blood sampling.
BOC is a compound which is currently in clinical development. It is expected to
be marketed in 2011. A total of >350 healthy volunteers have been exposed to
this drug already. The maximum single dose given to healthy volunteers was 800
mg; multiple doses up to 1200 mg TID were given to healthy subjects. The
longest dosing period was 56 days.
Possible adverse events in healthy volunteers are: dysgeusia, head-ache,
nausea, vomiting and elevated liver transaminases.
OME has been marketed since 1988. Common side effects (> 2%) are:
Headache, diarrhoea, abdominal pain, constipation, flatulence, nausea and
vomiting.
Geert Grooteplein Zuid 10
6525 GA Nijmegen
NL
Geert Grooteplein Zuid 10
6525 GA Nijmegen
NL
Listed location countries
Age
Inclusion criteria
1. Subject is at least 18 and not older than 55 years at screening.
2. Subject des not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to the first dosing
3. Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
4. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
5. Subject is in good age-appropriate health condition as estab-lished by medical history, physical examination, electrocardi-ography, 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.
6. Subject has a normal blood pressure and pulse rate, according to the Investigator's judgement.
Exclusion criteria
1. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
2. Positive HIV test.
3. Positive hepatitis B or C test.
4. 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.
5. Therapy with any drug (for two weeks preceding dosing), except for paracetamol.
6. 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.
7. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
8. History of or current abuse of drugs, alcohol or solvents.
9. Inability to understand the nature and extent of the trial and the procedures required.
10. Participation in a drug trial within 60 days prior to the first dose.
11. Donation of blood within 60 days prior to the first dose.
12. Febrile illness within 3 days before Day 1.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-024544-14-NL |
| CCMO | NL37305.091.11 |