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

The recruitment status of this study is unknown because the information has not been verified recently.
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
  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.

  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

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

Resource links provided by NLM:


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 ] [ 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:
  • 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
Genders Eligible for Study:   Both
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
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

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 April 15, 2014