Drug Interaction Between Coartem® and Nevirapine, Efavirenz or Rifampicin in HIV Positive Ugandan Patients
Recruitment status was Active, not recruiting
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Purpose
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.
- Comparison of steady state pharmacokinetics of Coartem® in HIV-infected patients prior to commencement of nevirapine and at nevirapine steady state
- Comparison of steady state pharmacokinetics of Coartem® in HIV-infected patients prior to commencement of efavirenz and at efavirenz steady state
- Comparison of steady state pharmacokinetics of Coartem® in Ugandan patients at rifampicin steady state and without rifampicin
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infections Tuberculosis |
Drug: Lumefantrine-artemether and nevirapine Drug: lumefantrine-artemether and efavirenz Drug: Lumefantrine-artemether and rifampicin |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Pharmacokinetic Interaction Between Coartem® and Either Nevirapine, Efavirenz or Rifampicin in HIV Positive Ugandan Patients |
- Pharmacokinetics of lumefantrine in patients receiving either nevirapine, efavirenz or rifampicin [ Time Frame: 11 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 90 |
| Study Start Date: | February 2008 |
| Estimated Study Completion Date: | July 2011 |
| Estimated Primary Completion Date: | July 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
nevirapine arm
|
Drug: Lumefantrine-artemether and nevirapine
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
Other Names:
|
|
Experimental: 2
efavirenz arm
|
Drug: lumefantrine-artemether and efavirenz
Administration of lumefantrine 480mg co-formulated with artemether 80mg twice daily for three days to HIV positive adults receiving efavirenz tablets 600mg once daily
Other Names:
|
|
Experimental: 3
Rifampicin arm
|
Drug: Lumefantrine-artemether and rifampicin
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
Other Name: Coartem
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age over eighteen years
- Ability to provide full written informed consent
- Confirmed diagnosis of HIV infection
Exclusion Criteria:
- 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
Contacts and Locations| Uganda | |
| Infectious Diseases Institute, Makerere University | |
| Kampala, Uganda, 22418 | |
| Principal Investigator: | Concepta Merry, PhD | Trinity Colleg Dublin |
More Information
No publications provided
| Responsible Party: | Concepta Merry, Infectious Diseases Institute, Makerere University |
| ClinicalTrials.gov Identifier: | NCT00620438 History of Changes |
| Other Study ID Numbers: | CPR 005 |
| Study First Received: | February 7, 2008 |
| Last Updated: | December 3, 2010 |
| Health Authority: | Uganda: National Council for Science and Technology |
Keywords provided by Makerere University:
|
Lumefantrine Efavirenz Nevirapine Rifampicin HIV |
Additional relevant MeSH terms:
|
HIV Infections Acquired Immunodeficiency Syndrome HIV Seropositivity Tuberculosis 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 Mycobacterium Infections Actinomycetales Infections |
Gram-Positive Bacterial Infections Bacterial Infections Rifampin Nevirapine Efavirenz Artemether Lumefantrine Artemether-lumefantrine combination Antibiotics, Antitubercular Anti-Bacterial Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Antitubercular Agents Enzyme Inhibitors |
ClinicalTrials.gov processed this record on June 18, 2013