Primary objectiveTo determine the effect of steady state boceprevir on the pharmacokinetics (AUC0-12h, Cmax, C12h) of a single dose raltegravir.Secondary objectives:To determine the effect of a single dose raltegravir on the pharmacokinetics (AUC0-…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetic parameters of raltegravir.
Secondary outcome
Pharmacokinetic parameters of boceprevir in comparison with historical
controls. Safety: adverse events en lab values.
Background summary
The prevalence of hepatitis C virus (HCV) in human immunodeficiency virus (HIV)
infected patients ranges from ± 7 to 57% in Europe and North America1. Since
the introduction of combination antiretroviral therapy (cART) the life
expectancy of HIV infected patients has improved dramatically. Since then,
hepatitis C has become one of the main causes of death among patients with
stable HIV.
Combined use of boceprevir and raltegravir is not expected to give a major
drug-drug interaction as raltegravir is not a CYP3A substrate and thus will not
be affected by the strong inhibition of CYP3A by bo-ceprevir. Raltegravir is
metabolized by UGT but boceprevir is not known to influence UGT. However,
recent data indicate that raltegravir is a P-gp substrate and boceprevir is a
substrate and a moderate inhibitor of P-gp in vitro.
Even when no drug interaction is expected, it may be recommended to collect
sufficient evidence that this is the case as in many cases un-expected
drug-drug interactions have been observed in the past.
Study objective
Primary objective
To determine the effect of steady state boceprevir on the pharmacokinetics
(AUC0-12h, Cmax, C12h) of a single dose raltegravir.
Secondary objectives:
To determine the effect of a single dose raltegravir on the pharmacokinetics
(AUC0-8h, Cmax, C8h) of steady state boceprevir (by comparison with historical
controls).
To study the safety of single-doses raltegravir combined with steady state
boceprevir.
Study design
Open-label, 2-period, randomized, cross-over, single-centre, phase-I trial
Group A will receive a single dose of 400mg RTG on Day 10. After a washout
period of at least two weeks they will take 800mg BOC TID (8 hours intervals)
with food for 9 days (Day 29-37). On day 38 they will receive a single dose of
400mg RTG and two doses of 800mg BOC (one together with RTG and one dose 8
hours later).
Group B will take 800mg BOC TID (8 hours intervals) with food for 9 days (Day
1-9). On day 10 they will receive a single dose of 400mg RTG and two doses of
800mg BOC (one together with RTG and one dose 8 hours later). After a washout
period of at least 4 weeks they will receive a single dose of 400mg RTG on Day
38.
The treatment group will be assigned at random.
On Days 10 and 38 a pharmacokinetic curve will be recorded.
Intervention
Dosing with raltegravir (two times a single dose of 400 mg) and boceprevir (9
days three times daily 800 mg and on day 10 two doses of 800 mg).
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) 5 times and stay for appr.
14 hours on two occasions. The duration of the entire trial (excluding
screening period) is 38 days.
A total number of 30 times a blood sample will be taken; the total volume taken
will be maximally 300mL.
During the days that blood samples will be collected for a pharmacokinetic
curve an intravenous cannula will be inserted to facilitate blood sampling.
Boceprevir is a compound which is still in clinical research. A total of 377
healthy volunteers have been exposed to this drug already. The maximum dose
given to healthy volunteers was 1200mg TID. The longest dosing period was 56
days.
Possible adverse events (in healthy volunteers) are: dysgeusia, anaemia,
headache, nausea, vomiting and elevated liver transaminases.
Raltegravir has been marketed since 2007. Common side effects (affects 1 to 10
users in 100):
• trouble sleeping; abnormal dreams
• feeling dizzy; headache
• spinning sensation
• bloating; abdominal pain; diarrhoea; excessive gas in the stomach or bowel;
feeling sick;
vomiting
• certain kinds of rash (more often when used in combination with darunavir)
• tiredness, unusual tiredness or weakness; fever
• increased liver blood tests; abnormal white blood cells; increased fat levels
in blood; increased level of enzyme from salivary glands or pancreas.
Possible side effects of the combination of boceprevir and raltegravir are
unknown.
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 does 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 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.
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 contracep-tion, 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 disorders (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 the first dose.
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 | EUCTR2010-024542-29-NL |
| CCMO | NL35464.091.11 |