Pharmacokinetic and Safety Study of Raltegravir and Atazanavir in a Once Daily Dose Regimen in HIV-1 Infected Patients (PRADA)

This study has been completed.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00943540
First received: July 21, 2009
Last updated: January 7, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
HIV Infection
HIV Infections
Drug: raltegravir QD
Drug: atazanavir
Drug: lamivudine (or emtricitabine)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetic and Safety Pilotstudy of RAltegravir and Atazanavir in a Once DAily Dose Regimen in HIV-1 Infected Patients (PRADA)

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • pharmacokinetics of raltegravir [ Time Frame: after two weeks of reference treatment and after two weeks of test treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Viral load [ Time Frame: after two weeks treatment with the reference treatment and after two weeks treatment with the test treatment ] [ Designated as safety issue: Yes ]
  • Adverse events [ Time Frame: entire trial ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: July 2009
Study Completion Date: January 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Raltegravir BID-QD

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
Drug: raltegravir QD
Raltegravir 800mg QD
Drug: atazanavir
atazanavir
Drug: lamivudine (or emtricitabine)
lamivudine (or emtricitabine)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00943540

Locations
Germany
University of Bonn
Bonn, Germany
Netherlands
Rijnstate Hospital Arnhem
Arnhem, Netherlands
Radboud University Medical Centre Nijmegen
Nijmegen, Netherlands
Erasmus Medical Center Rotterdam
Rotterdam, Netherlands
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: David Burger Radboud University
  More Information

No publications provided by Radboud University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: D.M. Burger, PhD, PharmD, Radboud University Medical Centre Nijmegen
ClinicalTrials.gov Identifier: NCT00943540     History of Changes
Other Study ID Numbers: UMCN-AKF 08.07
Study First Received: July 21, 2009
Last Updated: January 7, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
pharmacokinetics
single dose
raltegravir
Treatment experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lamivudine
Atazanavir
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014