Primary: To compare the pharmacokinetics of raltegravir 400 mg twice daily vs. ralte-gravir 800 mg once daily (QD) by intrasubject comparison. Secondary: To determine the efficacy of an antiretroviral regimen consisting of raltegravir 800mg QD,…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
comparison of raltegravir pharmacokinetics (AUC, Cmax and Cmin) after 2 weeks
of 400mg BID dosing versus 2 weeks of 800mg QD dosing.
Secondary outcome
viral load (efficacy), adverse events (safety).
Background summary
Anti-HIV-medication has to be used for life. Therefore it is of importance to
simplify the therapy as much as possible by reducing the dose frequency to once
daily dosing. Once daily dosing improves the quality of life and will increase
treatment compliance, reducing the risk on resistance to the drugs taken
(virological failure).
Study objective
Primary:
To compare the pharmacokinetics of raltegravir 400 mg twice daily vs.
ralte-gravir 800 mg once daily (QD) by intrasubject comparison.
Secondary:
To determine the efficacy of an antiretroviral regimen consisting of
raltegravir 800mg QD, atazanavir 600mg QD and lamivudine 300mg or emtricitabine
200mg QD in HIV-infected patients
To determine the safety of combined use of raltegravir and atazanavir QD in
HIV- infected patients
Study design
the trial will be conducted in 20 HIV-patients. The duration of the trial is 8
weeks, devided in two periods of four weeks each.
Treatment in the first period of 4 weeks:
-600 mg atazanavir QD
-400 mg raltegravir BID
-300 mg lamivudine QD or 200 mg emtricitabine QD
Blood concentrations of raltegravir and atazanavir will be determined after 2
weeks of treatment.
Evaluation at week 4: decision taken based on viral load and atazanavir blood
concentrations. After this evaluation the second period of 4 weeks will start.
Treatment in the second period of 4 weeks:
-600 mg atazanavir QD
-800 mg raltegravir QD
-300 mg lamivudine QD or 200 mg emtricitabine QD
Blood concentrations of raltegravir and atazanavir will be determined in week 6
of the trial (after 2 weeks of treatment).
Intervention
The treatment of patients will be adapted according to the schedule above.
There will be two days of blood sampling for pharmacokinetics.
Study burden and risks
Adverse events of the antiretroviral drugs. There is a chance that the HIV
virus will not be suppressed effectively. This will be monitored by regular
determination of viral load and atazanavir concentrations in the blood. If the
therapy is not effective the therapy will be adapted or the previous treatment
will be resumed.
The needles used for blood collection could inflict nuisance or pain at the
place of insertion. Blood collection will be done by qualified personnel.
The patients will come to the unit during two days on which blood sampling will
take place. The amount of blood collected during the study is small
(approximately 172 mL).
Geert Grooteplein Zuid 10
6525 GA Nijmegen
NL
Geert Grooteplein Zuid 10
6525 GA Nijmegen
NL
Listed location countries
Age
Inclusion criteria
1. HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot.
2. Subject is at least 18 years of age at the day of screening.
3. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
4. HIV-1 RNA < 40 copies/mL for at least 6 months on antiretroviral therapy.
5. Subject has no history of previous virological failure or documented resistance mutations.
Exclusion criteria
1. History of sensitivity/idiosyncrasy to the drug or chemically related compounds or excipients, which may be employed in the trial.
2. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
3. Inability to understand the nature and extent of the trial and the procedures re-quired.
4. Pregnant female (as confirmed by an HCG test performed less than 3 weeks before the first dose) or breast-feeding female.
5. Abnormal serum transminases determined as levels being > 5 times upper limit of normal (see Appendix A for normal ranges of clinical laboratory values).
6. Concomitant use of medications that interfere with raltegravir or atazanavir pharmacokinetics: rifampicin, irinotecan, midazolam, triazolam, ergotamine, dihydroergotamine, cisapride, pimozide, lovastain, simvastatin, indinavir, proton pump inhibitors, H2 receptor antagonists, St. john*s wort, Ginkgo Biloba, didanosine, tenofovir, efavirenz, nevirapine, antacids, clarithromycin, phenytoin, phenobarbital, carbamazepine.
7. Active hepatobiliary or hepatic disease (including chronic hepatitis B infection).
8. Alcohol abuse.
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 | EUCTR2008-008556-16-NL |
| CCMO | NL27841.091.09 |