Drug Interaction Study Between Atovaquone and Antiretroviral Agents in HIV-1 Infected Patients
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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) |
- 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.
- 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) |
![](https://webarchive.library.unt.edu/web/20130312225459im_/http://clinicaltrials.gov/ct2/html/images/frame/triangle.gif)
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
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
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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 |
Principal Investigator: | D.M. Burger, Dr. | Radboud University Medical Centre Nijmegen |
![](https://webarchive.library.unt.edu/web/20130312225459im_/http://clinicaltrials.gov/ct2/html/images/frame/triangle.gif)
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 March 10, 2013