Trial record 11 of 20 for:    " January 02, 2007":" February 02, 2007"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

Drug Interaction Study Between Atovaquone and Antiretroviral Agents in HIV-1 Infected Patients

This study has been completed.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00421473
First received: January 11, 2007
Last updated: February 24, 2009
Last verified: February 2009
  Purpose

Malarone® (atovaquone/proguanil) is frequently used in malaria prophylaxis. Unfortunately, there are indications that certain anti-HIV agents may decrease atovaquone plasma levels by induction of atovaquone metabolism.

For travelling HIV patients, the clinical consequences of these possible drug drug interactions are serious, since a diminished exposure to the anti-malarial drug will result in suboptimal prophylaxis of malaria and potential development of drug resistant strains of Plasmodium falciparum.

The purpose of this study is to find out if HIV patients using HAART regimes with either lopinavir/ritonavir, atazanavir/ritonavir or efavirenz have lower atovaquone plasma levels than healthy volunteers after a single dose of atovaquone/proguanil.


Condition Intervention Phase
HIV Infections
Malaria
Drug: Atovaquone / Proguanil
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Drug Interactions Between ATOvaquone Used in MAlaria Prophylaxis and Antiretroviral Agents in HIV-1 Infected Patients (ATOMA)

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Pharmacokinetic blood samples will be taken just before dosing Malarone, and 12 samples in the time between 0,5 hour and 168 hours after dosing.

Secondary Outcome Measures:
  • Blood will be taken for genotyping of CYP2C19 at study day 1.
  • HIV-1 RNA and CD4 determination will be done (HIV patients only) at inclusion screening

Enrollment: 79
Study Start Date: March 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

For healthy volunteers

  • 18 - 65 years
  • smoking habits < 10 cigarettes, 2 cigars or 2 pipes
  • BMI between 18 and 30 kg/m2
  • able and willing to sign informed consent form
  • subject is in a good age-appropriate health condition
  • subject has a normal blood pressure and pulse rate

For HIV patients

  • HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot.
  • CD4+ > 200 * 10E6 per Liter.
  • 18 - 65 years
  • BMI between 18 and 30 kg/m2
  • able and willing to sign informed consent form
  • use of lopinavir/ritonavir, atazanavir/ritonavir or efavirenz for at least 1 month in a dose of 400/100mg bid, 300/100 mg QD, or 600 mg QD respectively

Exclusion Criteria healthy volunteers:

  • History of sensitivity/idiosyncrasy to atovaquone/proguanil or chemically related compounds or excipients.
  • Positive HIV test.
  • Positive HbsAg test (hepatitis B) or positive hepatitis C test.
  • Therapy with any drug (for two weeks preceding dosing), except for paracetamol.
  • Creatinine clearance < 60 mL/min (calculated from serum creatinine)
  • Current diarrhoea.
  • Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
  • History of or current abuse of drugs, alcohol or solvents.
  • Inability to understand the nature and extent of the trial and the procedures required.
  • Participation in a drug trial within 60 days prior to the first dose.
  • Donation of blood within 60 days prior to the first dose.
  • 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 > 3 times up-per limit of normal
  • Febrile illness within 3 days before the first dose

Exclusion criteria HIV patients:

  • History of sensitivity/idiosyncrasy to atovaquone/proguanil or chemically related compounds or excipients.
  • Suspicion of non-adherence to the HIV medication.
  • Current diarrhoea.
  • 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 > 3 times upper limit of normal
  • Creatinine clearance < 60 mL/min (calculated from serum creatinine).
  • Any change in antiretroviral medication within 1 month immediately pre- ceding the dose of atovaquone/proguanil.
  • Concomitant use of medications that interfere with atovaquone or proguanil pharmacokinetics: anti-coagulants, aurothioglucose, chloroquine, cimetidine, fluoxetine, fluvoxamine, metoclopramide, omeprazole, magnesiumtrisilicate, rifabutin, rifampin, tetracycline, typhoid vaccine, topiramate.
  • Use of a HAART regime containing both lopinavir/ritonavir and another protease inhibitor or a NNRTI.
  • Use of a HAART regime containing both atazanavir/ritonavir and another protease inhibitor or a NNRTI.
  • Use of a HAART regime containing both efavirenz and one or more protease inhibitors or nevirapine.
  • Active hepatobiliary or hepatic disease
  • 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: NCT00421473

Locations
Netherlands
Elisabeth hospital
Tilburg, Brabant, Netherlands, 5022 GC
Alysis Zorggroep loc. Rijnstate
Arnhem, Gelderland, Netherlands, 6800 TA
Radboud University Medical Centre Nijmegen
Nijmegen, Gelderland, Netherlands, 6525 GA
Leids Universitair Medisch Centrum
Leiden, Zuid Holland, Netherlands, 2300 RC
Erasmus MC
Rotterdam, Zuid Holland, Netherlands, 3000 CA
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: D.M. Burger, Dr. Radboud University Medical Centre Nijmegen
  More Information

No publications provided by Radboud University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00421473     History of Changes
Other Study ID Numbers: UMCN-AKF 06.02
Study First Received: January 11, 2007
Last Updated: February 24, 2009
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
HIV
Malaria prophylaxis
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Malaria
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
Protozoan Infections
Parasitic Diseases
Proguanil
Atovaquone
Malarone
Anti-Retroviral Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Antiviral Agents

ClinicalTrials.gov processed this record on July 23, 2014