Pharmacokinetic and Safety Study of Raltegravir and Atazanavir in a Once Daily Dose Regimen in HIV-1 Infected Patients
PRADA
Pharmacokinetic and Safety Pilotstudy of RAltegravir and Atazanavir in a Once DAily Dose Regimen in HIV-1 Infected Patients (PRADA)
1 other identifier
interventional
20
2 countries
4
Brief Summary
The licensed dose of raltegravir is 400 mg twice daily with or without food. Raltegravir is metabolized predominantly through glucuronidation by UGT1A1. Atazanavir increases the plasma concentrations of raltegravir 400 mg twice daily by 72% due to inhibition of UGT 1A1. This suggests that combined use of atazanavir and a lower dose frequency of raltegravir, once daily for example, is possible. Another reason why raltegravir most likely can be applied is that its pharmacodynamic effect is not related to Cmin but to AUC which is expected to be similar for an 800mg QD dose when compared to 400mg BD. Phase III clinical trials evaluating QD dosing of raltegravir are currently ongoing and interim results are expected to be published in mid 2009. A regimen of atazanavir and raltegravir in combination with lamivudine or emtricitabine may be a well tolerated and effective NNRTI-, and ritonavir-sparing regimen that could be an attractive option for both first and second line (after NRTI/NNRTI failure) treatment regimens.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jul 2009
Shorter than P25 for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2009
CompletedFirst Submitted
Initial submission to the registry
July 21, 2009
CompletedFirst Posted
Study publicly available on registry
July 22, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2011
CompletedNovember 12, 2020
November 1, 2020
1.4 years
July 21, 2009
November 9, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
pharmacokinetics of raltegravir
after two weeks of reference treatment and after two weeks of test treatment
Secondary Outcomes (2)
Viral load
after two weeks treatment with the reference treatment and after two weeks treatment with the test treatment
Adverse events
entire trial
Study Arms (1)
Raltegravir BID-QD
EXPERIMENTALWeek 1-4 * 600 mg of atazanavir to be taken once daily * 400 mg of raltegravir to be taken twice daily * 300 mg of lamivudine (or 200 mg of emtricitabine) to be taken once daily Week 5-8 * 600 mg of atazanavir to be taken once daily * 800 mg of raltegravir to be taken once daily * 300 mg of lamivudine (or 200 mg of emtricitabine) to be taken once daily
Interventions
Eligibility Criteria
You may qualify if:
- HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot.
- Subject is at least 18 years of age at the day of screening.
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
- HIV-1 RNA \< 40 copies/mL for at least 6 months on antiretroviral therapy.
- Subject has no history of previous virological failure or documented resistance mutations
You may not qualify if:
- History of sensitivity/idiosyncrasy to the drug or chemically related compounds or excipients, which may be employed in the trial.
- Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
- Inability to understand the nature and extent of the trial and the procedures required.
- Pregnant female (as confirmed by an HCG test performed less than 3 weeks before the first dose) or breast-feeding female.
- Abnormal serum transaminases determined as levels being \> 5 times upper limit of normal (see Appendix A for normal ranges of clinical laboratory values).
- Concomitant use of medications that interfere with raltegravir or atazanavir pharmacokinetics: rifampicin, irinotecan, midazolam, triazolam, ergotamine, dihydroergotamine, cisapride, pimozide, lovastatin, simvastatin, indinavir, proton pump inhibitors, H2 receptor antagonists, St. john's wort, Ginkgo Biloba, didanosine, tenofovir, efavirenz, nevirapine, antacids, clarithromycin, phenytoin, phenobarbital, carbamazepine.
- Active hepatobiliary or hepatic disease (including chronic hepatitis B infection).
- Alcohol abuse.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
University of Bonn
Bonn, Germany
Rijnstate Hospital Arnhem
Arnhem, Netherlands
Radboud University Medical Centre Nijmegen
Nijmegen, Netherlands
Erasmus Medical Center Rotterdam
Rotterdam, Netherlands
Related Publications (1)
Jansen A, Colbers EP, van der Ven AJ, Richter C, Rockstroh JK, Wasmuth JC, van Luin M, Burger DM. Pharmacokinetics of the combination raltegravir/atazanavir in HIV-1-infected patients. HIV Med. 2013 Aug;14(7):449-52. doi: 10.1111/hiv.12029. Epub 2013 Mar 18.
PMID: 23506243RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
David Burger
Radboud University Medical Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
July 21, 2009
First Posted
July 22, 2009
Study Start
July 1, 2009
Primary Completion
December 1, 2010
Study Completion
January 1, 2011
Last Updated
November 12, 2020
Record last verified: 2020-11