Pharmacokinetic and Safety Study of Raltegravir and Atazanavir in a Once Daily Dose Regimen in HIV-1 Infected Patients (PRADA)
Primary Purpose
HIV Infection, HIV Infections
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
raltegravir QD
atazanavir
lamivudine (or emtricitabine)
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infection focused on measuring pharmacokinetics, single dose, raltegravir, Treatment experienced
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- University of Bonn
- Rijnstate Hospital Arnhem
- Radboud University Medical Centre Nijmegen
- Erasmus Medical Center Rotterdam
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Raltegravir BID-QD
Arm Description
Week 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
Outcomes
Primary Outcome Measures
pharmacokinetics of raltegravir
Secondary Outcome Measures
Viral load
Adverse events
Full Information
NCT ID
NCT00943540
First Posted
July 21, 2009
Last Updated
November 9, 2020
Sponsor
Radboud University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT00943540
Brief Title
Pharmacokinetic and Safety Study of Raltegravir and Atazanavir in a Once Daily Dose Regimen in HIV-1 Infected Patients
Acronym
PRADA
Official Title
Pharmacokinetic and Safety Pilotstudy of RAltegravir and Atazanavir in a Once DAily Dose Regimen in HIV-1 Infected Patients (PRADA)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
January 2011 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Radboud University Medical Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection, HIV Infections
Keywords
pharmacokinetics, single dose, raltegravir, Treatment experienced
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Raltegravir BID-QD
Arm Type
Experimental
Arm Description
Week 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
Intervention Type
Drug
Intervention Name(s)
raltegravir QD
Intervention Description
Raltegravir 800mg QD
Intervention Type
Drug
Intervention Name(s)
atazanavir
Intervention Description
atazanavir
Intervention Type
Drug
Intervention Name(s)
lamivudine (or emtricitabine)
Intervention Description
lamivudine (or emtricitabine)
Primary Outcome Measure Information:
Title
pharmacokinetics of raltegravir
Time Frame
after two weeks of reference treatment and after two weeks of test treatment
Secondary Outcome Measure Information:
Title
Viral load
Time Frame
after two weeks treatment with the reference treatment and after two weeks treatment with the test treatment
Title
Adverse events
Time Frame
entire trial
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Burger
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Bonn
City
Bonn
Country
Germany
Facility Name
Rijnstate Hospital Arnhem
City
Arnhem
Country
Netherlands
Facility Name
Radboud University Medical Centre Nijmegen
City
Nijmegen
Country
Netherlands
Facility Name
Erasmus Medical Center Rotterdam
City
Rotterdam
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
23506243
Citation
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.
Results Reference
result
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Pharmacokinetic and Safety Study of Raltegravir and Atazanavir in a Once Daily Dose Regimen in HIV-1 Infected Patients
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