Drug Interaction Between Coartem® and Nevirapine, Efavirenz or Rifampicin in HIV Positive Ugandan Patients
Pharmacokinetic Interaction Between Coartem® and Either Nevirapine, Efavirenz or Rifampicin in HIV Positive Ugandan Patients
1 other identifier
interventional
90
1 country
1
Brief Summary
There are increasing numbers of HIV-infected patients in sub-Saharan Africa receiving antiretroviral drugs and/or rifampicin based antituberculous therapy. HIV infected patients are at an increased risk of contracting malaria. Increasing resistance to anti-malarials such as chloroquine, amodiaquine, fansidar, sulphadoxine-pyrimethamine in East and West Africa has led the WHO to recommend artemether-lumefantrine (Coartem®- Novartis) as first line therapy for malaria for adults and children. As early as 2004, fourteen countries in sub-Saharan Africa had adopted this guideline as national policy. There are no data on the interaction between Coartem® and any of the antiretroviral agents. Both components of Coartem® are substrates for the 3A4 isoform of cytochrome P450. Despite the lack of data, antiretroviral drugs and/or antituberculous drugs in addition to Coartem® are of necessity co-prescribed daily in the African setting. Nevirapine, efavirenz and rifampicin are known inducers of cytochrome P450 3A4. A technical consultation convened by WHO in June, 2004 concluded that additional research on interactions between antiretroviral and antimalarial drugs is urgently needed. We propose to perform a suite of pharmacokinetic studies to evaluate these interactions in HIV infected Ugandan patients. The aim of these studies is to evaluate the pharmacokinetic interaction between Coartem® and commonly co-prescribed inducers of 3A4 i.e. nevirapine, efavirenz and rifampicin.
- 1.Comparison of steady state pharmacokinetics of Coartem® in HIV-infected patients prior to commencement of nevirapine and at nevirapine steady state
- 2.Comparison of steady state pharmacokinetics of Coartem® in HIV-infected patients prior to commencement of efavirenz and at efavirenz steady state
- 3.Comparison of steady state pharmacokinetics of Coartem® in Ugandan patients at rifampicin steady state and without rifampicin
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4 hiv-infections
Started Feb 2008
Typical duration for phase_4 hiv-infections
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2008
CompletedFirst Submitted
Initial submission to the registry
February 7, 2008
CompletedFirst Posted
Study publicly available on registry
February 21, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2011
CompletedDecember 6, 2010
December 1, 2010
3.4 years
February 7, 2008
December 3, 2010
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Pharmacokinetics of lumefantrine in patients receiving either nevirapine, efavirenz or rifampicin
11 months
Study Arms (3)
1
EXPERIMENTALnevirapine arm
2
EXPERIMENTALefavirenz arm
3
EXPERIMENTALRifampicin arm
Interventions
Administration of lumefantrine 480mg co-formulated with artemether 80mg twice daily for three days to HIV positive patients receiving nevirapine 200mg twice daily as part of their antiretroviral treatment
Administration of lumefantrine 480mg co-formulated with artemether 80mg twice daily for three days to HIV positive adults receiving efavirenz tablets 600mg once daily
Administration of lumefantrine 480mg co-formulated with artemether 80mg twice daily for three days to patients receiving rifampicin as part of fixed dose combination therapy for tuberculosis
Eligibility Criteria
You may qualify if:
- Age over eighteen years
- Ability to provide full written informed consent
- Confirmed diagnosis of HIV infection
You may not qualify if:
- Haemoglobin \< 8g/dl
- Liver and renal function tests \> 3 times the upper limit of normal
- Pregnancy
- Use of known inhibitors or inducers of cytochrome P450 or P-glycoprotein.
- Use of herbal medications (information will be obtained from patients' medication history through interview with the patient)
- Abnormal EKG ie QTc (Rate adjusted QT interval) \>450ms (men) or \>470ms (women)
- Intercurrent Illness including malaria
- Known hypersensitivity to artemisinin-derivatives, halofantrine or lumefantrine
- History of cardiac disease
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Makerere Universitylead
- Health Research Board, Irelandcollaborator
Study Sites (1)
Infectious Diseases Institute, Makerere University
Kampala, 22418, Uganda
Related Publications (1)
Hoglund RM, Byakika-Kibwika P, Lamorde M, Merry C, Ashton M, Hanpithakpong W, Day NP, White NJ, Abelo A, Tarning J. Artemether-lumefantrine co-administration with antiretrovirals: population pharmacokinetics and dosing implications. Br J Clin Pharmacol. 2015 Apr;79(4):636-49. doi: 10.1111/bcp.12529.
PMID: 25297720DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Concepta Merry, PhD
Trinity Colleg Dublin
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
February 7, 2008
First Posted
February 21, 2008
Study Start
February 1, 2008
Primary Completion
July 1, 2011
Study Completion
July 1, 2011
Last Updated
December 6, 2010
Record last verified: 2010-12