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

November 9, 2020 updated by: Radboud University Medical Center

Drug Interactions Between ATOvaquone Used in MAlaria Prophylaxis and Antiretroviral Agents in HIV-1 Infected Patients (ATOMA)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

79

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Brabant
      • Tilburg, Brabant, Netherlands, 5022 GC
        • Elisabeth Hospital
    • Gelderland
      • Arnhem, Gelderland, Netherlands, 6800 TA
        • Alysis Zorggroep loc. Rijnstate
      • Nijmegen, Gelderland, Netherlands, 6525 GA
        • Radboud University Medical Centre Nijmegen
    • Zuid Holland
      • Leiden, Zuid Holland, Netherlands, 2300 RC
        • Leids Universitair Medisch Centrum
      • Rotterdam, Zuid Holland, Netherlands, 3000 CA
        • Erasmus MC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Investigators

  • Principal Investigator: D.M. Burger, Dr., Radboud University Medical Centre Nijmegen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

December 1, 2008

Study Registration Dates

First Submitted

January 11, 2007

First Submitted That Met QC Criteria

January 11, 2007

First Posted (Estimate)

January 12, 2007

Study Record Updates

Last Update Posted (Actual)

November 12, 2020

Last Update Submitted That Met QC Criteria

November 9, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCN-AKF 06.02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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