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Drug Interaction Study Between Lumefantrine and Lopinavir/Ritonavir

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ClinicalTrials.gov Identifier: NCT00619944
Recruitment Status : Completed
First Posted : February 21, 2008
Last Update Posted : December 6, 2010
University of Liverpool
Information provided by:
Makerere University

Brief Summary:
With the roll out of antiretroviral therapy (ARV) for HIV across sub-Saharan Africa an unprecedented number of people will be commencing lifelong therapy. Current estimates are that 5-6 million people in sub-Saharan Africa require ART. At the same time, the World Health Organization (WHO) Roll Back Malaria campaign is aggressively promoting the use of artemether/lumefantrine as first-line therapy for malaria in this setting. Many patients in this setting have already become resistant to first-line ARV and have moved onto lopinavir/ritonavir (Kaletra) based second-line regimens. Kaletra is a potent inhibitor of Cytochrome P450 3A4 (CYP 3A4), an enzyme responsible for the metabolism of many drugs which is found predominantly in the liver and the gut. Lumefantrine, and to a lesser extent artemether, is extensively metabolized by CYP 3A4. Therefore when given to a patient already taking Kaletra for HIV, it is likely that elevated levels of these drugs in the patient will result. There is some concern that lumefantrine may be cardiotoxic due to its structural similarity to halofantrine which is known to cause irregular heart rhythms. This has not been borne out as yet in any studies performed with lumefantrine, however it is not known what levels will be achieved in patients when it is administered with a protease inhibitor such as Kaletra. The WHO has not addressed this issue in any of its previous policy documents but has identified ARV-antimalarial drug interaction studies as a research priority. This single dose pharmacokinetic (PK) study aims to compare the levels of lumefantrine/artemether that result when it is given to a patient on Kaletra with patients not on any ARV. Data generated by this study will help address this important knowledge gap which has been identified by WHO and others as meriting urgent investigation.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Lumefantrine - lopinavir/ritonavir drug interaction Drug: Lumefantrine only arm Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Lumefantrine Pharmacokinetics When Administered as a Fixed Dose Combination With Artemether in HIV Positive Patients on Lopinavir/Ritonavir
Study Start Date : February 2008
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1
Lumefantrine lopinavir drug interaction arm
Drug: Lumefantrine - lopinavir/ritonavir drug interaction
Lumefantrine 480 mg co-formulated with artemether 80 mg administered as single dose to HIV-positive adults receiving lopinavir/ritonavir 400 mg/100 mg twice daily
Other Names:
  • Coartem tablets
  • Kaletra/Aluvia tablets

Active Comparator: 2
lumefantrine only arm
Drug: Lumefantrine only arm
Lumefantrine 480 mg co-formulated with artemether 80 mg administered as a single dose to antiretroviral naive HIV-positive patients
Other Name: Coartem tablets

Primary Outcome Measures :
  1. 12 hour pharmacokinetics profile of lumefantrine in HIV-positive patients receiving lopinavir/ritonavir [ Time Frame: 11 months ]

Secondary Outcome Measures :
  1. Safety and tolerability of lumefantrine/artemether in HIV-positive Ugandan patients receiving lopinavir/ritonavir [ Time Frame: 11 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age over eighteen
  • Ability to provide full informed written consent
  • Confirmed diagnosis of HIV infection

Exclusion Criteria:

  • Haemoglobin < 8 g/dl
  • HIV RNA (Viral Load) > 400 c/ml (if on antiretroviral therapy)
  • Malaria Parasitaemia
  • 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
  • QTc (Rate adjusted QT interval) > 450 ms (men) or > 470 ms (women)
  • Intercurrent illness including malaria

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): NCT00619944

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Infectious Diseases Institute, Faculty of Medicine, Makerere University
Kampala, Uganda, 22418
Sponsors and Collaborators
Makerere University
University of Liverpool
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Principal Investigator: Concepta A. Merry, PhD University of Dublin, Trinity College
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Concepta Merry, Infectious Diseases Institute
ClinicalTrials.gov Identifier: NCT00619944    
Other Study ID Numbers: CPR 003
First Posted: February 21, 2008    Key Record Dates
Last Update Posted: December 6, 2010
Last Verified: December 2010
Keywords provided by Makerere University:
treatment naïve
Additional relevant MeSH terms:
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HIV Infections
Blood-Borne Infections
Communicable Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Artemether, Lumefantrine Drug Combination
HIV Protease Inhibitors
Viral Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antiprotozoal Agents
Antiparasitic Agents