We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00620438
Recruitment Status : Unknown
Verified December 2010 by Makerere University.
Recruitment status was:  Active, not recruiting
First Posted : February 21, 2008
Last Update Posted : December 6, 2010
Sponsor:
Collaborator:
Information provided by:

Study Description
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

Condition or disease Intervention/treatment Phase
HIV Infections Tuberculosis Drug: Lumefantrine-artemether and nevirapine Drug: lumefantrine-artemether and efavirenz Drug: Lumefantrine-artemether and rifampicin Phase 4

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
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
Study Start Date : February 2008
Estimated Primary Completion Date : July 2011
Estimated Study Completion Date : July 2011


Arms and Interventions

Arm Intervention/treatment
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


Outcome Measures

Primary Outcome Measures :
  1. Pharmacokinetics of lumefantrine in patients receiving either nevirapine, efavirenz or rifampicin [ Time Frame: 11 months ]

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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):
Responsible Party: Concepta Merry, Infectious Diseases Institute, Makerere University
ClinicalTrials.gov Identifier: NCT00620438     History of Changes
Other Study ID Numbers: CPR 005
First Posted: February 21, 2008    Key Record Dates
Last Update Posted: December 6, 2010
Last Verified: December 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