Drug Interaction Study Between Atovaquone and Antiretroviral Agents in HIV-1 Infected Patients
Information source: Radboud University
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; Malaria
Intervention: Atovaquone / Proguanil (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Radboud University Official(s) and/or principal investigator(s):
D.M. Burger, Dr., Principal Investigator, Affiliation: Radboud University Medical Centre Nijmegen
Overall contact:
Matthijs v Luin, Drs, Phone: 0031-26-3786327, Email: mvanluin@alysis.nl
Summary
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.
Clinical Details
Official title: Drug Interactions Between ATOvaquone Used in MAlaria Prophylaxis and Antiretroviral Agents in HIV-1 Infected Patients (ATOMA)
Study design: Prevention, Non-Randomized, Open Label, Active Control, Parallel Assignment, Pharmacokinetics Study
Primary outcome: 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: 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
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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
Locations and Contacts
Matthijs v Luin, Drs, Phone: 0031-26-3786327, Email: mvanluin@alysis.nl
University of Cologne, Cologne, Germany; Not yet recruiting
G. Faetkenheuer, Prof. Dr., Principal Investigator
University of Bonn, Bonn, Germany; Not yet recruiting
J. Rockstroh, Prof. Dr., Principal Investigator
Elisabeth hospital, Tilburg, Brabant 5022 GC, Netherlands; Recruiting
M Kuipers, Phone: 0031-13-5393138, Email: m.kuipers@elisabeth.nl
M.E.E. v Kasteren, Drs., Principal Investigator
Radboud University Medical Centre Nijmegen, Nijmegen, Gelderland 6525 GA, Netherlands; Recruiting
M Bosch, Phone: 0031-24-3615077, Email: m.bosch@cispoli.umcn.nl
P. Koopmans, Dr., Principal Investigator
Alysis Zorggroep loc. Rijnstate, Arnhem, Gelderland 6800 TA, Netherlands; Recruiting
N. Langenbeek, Drs., Phone: 0031-26-3788888, Email: Nlangebeek@alysis.nl
C Richter, Dr., Principal Investigator
Erasmus MC, Rotterdam, Zuid Holland 3000 CA, Netherlands; Recruiting
M Bendik, Email: m.bendik@erasmusmc.nl
M.E. vd Ende, Dr., Principal Investigator
Leids Universitair Medisch Centrum, Leiden, Zuid Holland 2300 RC, Netherlands; Recruiting
L.B.S. Gelinck, Dr., Email: L.B.S.Gelinck@lumc.nl
F.P. Kroon, Dr., Principal Investigator
Additional Information
Starting date: March 2007
Ending date: July 2008
Last updated: October 21, 2008
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