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Sponsors and Collaborators: |
Makerere University University of Liverpool |
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Information provided by: | Makerere University |
ClinicalTrials.gov Identifier: | NCT00619944 |
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 | Intervention | Phase |
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HIV Infections |
Drug: Lumefantrine - lopinavir/ritonavir drug interaction Drug: Lumefantrine only arm |
Phase IV |
Study Type: | Interventional |
Study Design: | Basic Science, Non-Randomized, Open Label, Parallel Assignment, Pharmacokinetics Study |
Official Title: | Lumefantrine Pharmacokinetics When Administered as a Fixed Dose Combination With Artemether in HIV Positive Patients on Lopinavir/Ritonavir |
Estimated Enrollment: | 32 |
Study Start Date: | February 2008 |
Estimated Study Completion Date: | March 2009 |
Estimated Primary Completion Date: | December 2008 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Lumefantrine lopinavir drug interaction arm
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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
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2: Active Comparator
lumefantrine only arm
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Drug: Lumefantrine only arm
Lumefantrine 480 mg co-formulated with artemether 80 mg administered as a single dose to antiretroviral naive HIV-positive patients
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Ages Eligible for Study: | 18 Years to 60 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Concepta A. Merry, PhD | 256 414 307224 | cmerry@tcd.ie |
Contact: Pauline Byakika-Kibwika, MMed | 256 414 307224 | pbyakika@idi.co.ug |
Uganda | |
Infectious Diseases Institute, Faculty of Medicine, Makerere University | Recruiting |
Kampala, Uganda, 22418 | |
Contact: Pauline Byakika-Kibwika, MMed 256 414 307224 pbyakika@idi.co.ug | |
Sub-Investigator: Pauline Byakika-Kibwika, MMed | |
Sub-Investigator: Mohammed Lamorde, MBBS | |
Sub-Investigator: Moses Kamya, MMed | |
Sub-Investigator: Paul Waako, PhD | |
Sub-Investigator: Peter Lwabi, MMed |
Principal Investigator: | Concepta A. Merry, PhD | Trinity College Dublin |
Responsible Party: | Infectious Diseases Institute ( Concepta Merry ) |
Study ID Numbers: | CPR 003 |
Study First Received: | February 7, 2008 |
Last Updated: | November 6, 2008 |
ClinicalTrials.gov Identifier: | NCT00619944 History of Changes |
Health Authority: | Uganda: National Council for Science and Technology |
HIV lumefantrine lopinavir |
Africa Antimalarials treatment naïve |
Benflumetol Artemether-lumefantrine combination HIV Protease Inhibitors Sexually Transmitted Diseases, Viral Anti-HIV Agents Acquired Immunodeficiency Syndrome Antiviral Agents Immunologic Deficiency Syndromes Protease Inhibitors Artemether |
Virus Diseases Antimalarials Anti-Retroviral Agents Lopinavir HIV Seropositivity HIV Infections Ritonavir Sexually Transmitted Diseases Retroviridae Infections |
Benflumetol Anti-Infective Agents Antiprotozoal Agents Sexually Transmitted Diseases, Viral Slow Virus Diseases Molecular Mechanisms of Pharmacological Action Infection Antimalarials Antiparasitic Agents Lopinavir Anti-Retroviral Agents Therapeutic Uses Retroviridae Infections RNA Virus Infections |
HIV Protease Inhibitors Anti-HIV Agents Immune System Diseases Acquired Immunodeficiency Syndrome Enzyme Inhibitors Antiviral Agents Immunologic Deficiency Syndromes Pharmacologic Actions Protease Inhibitors Virus Diseases Ritonavir HIV Infections Sexually Transmitted Diseases Lentivirus Infections |