Primary objective: To evaluate the influence of fosamprenavir/ritonavir on single-dose pharmacokinetics of olanzapine in healthy volunteersSecondary objective: To evaluate the safety of fosamprenavir/ritonavir combined with single-dose olanzapine in…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Schizophrenia and other psychotic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The influence of fosamprenavir/ritonavir on single-dose pharmacokinetics of
olanzapine in healthy volunteers
Secondary outcome
The safety of fosamprenavir/ritonavir combined with single-dose olanzapine in
healthy volunteers
Background summary
Psychosis and other mental illnesses are commonly described in patients
infected with the human immunodeficiency virus (HIV). The high rates of
co-morbidity of mental illness and HIV can be partly explained by the risk
behaviour of patients with mental illness. Furthermore, having an
HIV-infection, places people at risk for developing psychoses.
When psychosis is present in HIV-infected people (either new-onset or existing
psychosis), treatment with an antipsychotic agent is usually necessary.
HIV-infected patients with new-onset psychosis generally respond well to
antipsychotic medication, but are extra sensitive for their side-effects,
especially extrapyridamal side effects (EPS) and tardive dyskinesia (TD)
induced by conventional antipsychotics. Because of their favourable side-effect
profile, atypical antipsychotic agents are preferable in HIV-infected people.
Olanzapine could be an attractive antipsychotic in HIV/AIDS patients with
schizophrenia. However, there is little experience with olanzapine in treating
schizophrenia in HIV/AIDS patients. Further, olanzapine is metabolised by
uridine diphosphate-glucuronosyltransferase (UGT) and CYP1A2, which puts it at
risk for pharmacokinetic interactions with HIV-medication. Fosamprenavir is a
protease-inhibitor (PI) that is used to treat HIV-infection in combina-tion
with ritonavir. Ritonavir has many influences on the diverse CYP-enzymes, among
which CYP1A2 and UGT. Because olanzapine is a substrate for both UGT and
CYP1A2, the pharmacokinetics of olanzapine might be influenced by low-dose
ritonavir in combination with fosamprenavir.
Study objective
Primary objective:
To evaluate the influence of fosamprenavir/ritonavir on single-dose
pharmacokinetics of olanzapine in healthy volunteers
Secondary objective:
To evaluate the safety of fosamprenavir/ritonavir combined with single-dose
olanzapine in healthy volunteers
Study design
Open-label, 2-period, randomized, cross-over, single centre, phase-I trial
Intervention
Two groups are defined for treatment.
Group 1:
Day 1-16: Fosamprenavir/ritonavir 700/100 mg BD Day + olanzapine 15 mg
single-dose on Day 13
Day 17-47:wash-out
Day 48: single-dose olanzapine 10 mg on Day 48
Group 2:
Day 13: single-dose olanzapine 10 mg
Day 14-35: wash-out
Day 36-52: fosamprenavir/ritonavir 700/100 BD + olanzapine single-dose 15 mg on
Day 48
After the morning dosage on Day 13 and Day 48 a 96h pharmacokinetic curve (17
samples) will be performed
Study burden and risks
The needles used for blood sample collection may cause slight discomfort at the
injection site.
The healthy volunteers may experience adverse events of the trial medication.
The risks for adverse events are minimalized by limiting the use of
fosampravir/ritonavir to 16 days and limiting the use of olanzapine to 2 times
a single-dose. Study subjects will be monitored almost every other day, and
adverse events can be detected early. The information we will collect from this
study outweighs the risks for toxicity in healthy volunteers.
Geert Grooteplein Zuid 10
6525 GA Nijmegen
Nederland
Geert Grooteplein Zuid 10
6525 GA Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
1. Subject is at least 18 and not older than 55 years of age at screening.
2. Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes in- cluded.
3. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
4. Subject is in good age-appropriate health condition as established by medical his-tory, physical examination, electrocardiography, results of biochemistry, haema-tology and urinalysis testing within 4 weeks prior to the first dose. Results of bio-chemistry, 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.
5. Subject has a normal blood pressure and pulse rate, according to the Investiga-tor'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 be-fore the first dose) or breast-feeding female. Female subjects of childbearing po-tential 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), cardio-vascular disorders, neurological disorders (especially seizures and migraine), gas-tro-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 re-quired.
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
13. History of narrow-angle glaucoma
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 | EUCTR2009-009430-32-NL |
| CCMO | NL27936.091.09 |