Drug Interaction Study Between Lumefantrine and Lopinavir/Ritonavir
Status:
Completed
Trial end date:
2008-12-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 4
Details
Lead Sponsor:
Makerere University
Collaborator:
University of Liverpool
Treatments:
Artemether Artemether-lumefantrine combination Artemether, Lumefantrine Drug Combination Lopinavir Lumefantrine Ritonavir