Drug Interaction Between Coartem® and Nevirapine, Efavirenz or Rifampicin in HIV Positive Ugandan Patients

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.

Verified December 2010 by Makerere University.
Recruitment status was: Active, not recruiting

Sponsor:

Collaborator:

Health Research Board, Ireland

Information provided by:

Makerere University

ClinicalTrials.gov Identifier:

NCT00620438

First received: February 7, 2008

Last updated: December 3, 2010

Last verified: December 2010

History of Changes

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 Intervention Model: Crossover Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	Pharmacokinetic Interaction Between Coartem® and Either Nevirapine, Efavirenz or Rifampicin in HIV Positive Ugandan Patients

Resource links provided by NLM:

MedlinePlus related topics: Drug Reactions HIV/AIDS

Drug Information available for: Rifampin Artemether Lumefantrine Nevirapine Efavirenz

Genetic and Rare Diseases Information Center resources: Tuberculosis

U.S. FDA Resources

Further study details as provided by Makerere University:

Primary Outcome Measures:

Pharmacokinetics of lumefantrine in patients receiving either nevirapine, efavirenz or rifampicin [ Time Frame: 11 months ]


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: Coartem Triomune
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: Coartem Sustiva
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 (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00620438

Locations


Uganda
Infectious Diseases Institute, Makerere University
Kampala, Uganda, 22418

Sponsors and Collaborators

Makerere University

Health Research Board, Ireland

Investigators


Principal Investigator:	Concepta Merry, PhD	Trinity Colleg Dublin

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hoglund RM, Byakika-Kibwika P, Lamorde M, Merry C, Ashton M, Hanpithakpong W, Day NP, White NJ, Äbelö 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.


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

Keywords provided by Makerere University:


Lumefantrine Efavirenz Nevirapine Rifampicin HIV

Additional relevant MeSH terms:


HIV Infections Tuberculosis Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Efavirenz	Nevirapine Rifampin Lumefantrine Artemether Artemether-lumefantrine combination Artemisinins Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 20, 2017

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