Drug Interaction Study Between Lumefantrine and Lopinavir/Ritonavir
Lumefantrine Pharmacokinetics When Administered as a Fixed Dose Combination With Artemether in HIV Positive Patients on Lopinavir/Ritonavir
1 other identifier
interventional
32
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_4 hiv-infections
Started Feb 2008
Shorter than P25 for phase_4 hiv-infections
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2008
CompletedFirst Submitted
Initial submission to the registry
February 7, 2008
CompletedFirst Posted
Study publicly available on registry
February 21, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2008
CompletedDecember 6, 2010
December 1, 2010
10 months
February 7, 2008
December 3, 2010
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
12 hour pharmacokinetics profile of lumefantrine in HIV-positive patients receiving lopinavir/ritonavir
11 months
Secondary Outcomes (1)
Safety and tolerability of lumefantrine/artemether in HIV-positive Ugandan patients receiving lopinavir/ritonavir
11 months
Study Arms (2)
1
EXPERIMENTALLumefantrine lopinavir drug interaction arm
2
ACTIVE COMPARATORlumefantrine only arm
Interventions
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
Lumefantrine 480 mg co-formulated with artemether 80 mg administered as a single dose to antiretroviral naive HIV-positive patients
Eligibility Criteria
You may qualify if:
- Age over eighteen
- Ability to provide full informed written consent
- Confirmed diagnosis of HIV infection
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Makerere Universitylead
- University of Liverpoolcollaborator
Study Sites (1)
Infectious Diseases Institute, Faculty of Medicine, Makerere University
Kampala, 22418, Uganda
Related Publications (2)
Hoglund RM, Byakika-Kibwika P, Lamorde M, Merry C, Ashton M, Hanpithakpong W, Day NP, White NJ, Abelo A, Tarning J. Artemether-lumefantrine co-administration with antiretrovirals: population pharmacokinetics and dosing implications. Br J Clin Pharmacol. 2015 Apr;79(4):636-49. doi: 10.1111/bcp.12529.
PMID: 25297720DERIVEDByakika-Kibwika P, Lamorde M, Okaba-Kayom V, Mayanja-Kizza H, Katabira E, Hanpithakpong W, Pakker N, Dorlo TP, Tarning J, Lindegardh N, de Vries PJ, Back D, Khoo S, Merry C. Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults. J Antimicrob Chemother. 2012 May;67(5):1217-23. doi: 10.1093/jac/dkr596. Epub 2012 Feb 8.
PMID: 22316571DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Concepta A. Merry, PhD
University of Dublin, Trinity College
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
February 7, 2008
First Posted
February 21, 2008
Study Start
February 1, 2008
Primary Completion
December 1, 2008
Study Completion
December 1, 2008
Last Updated
December 6, 2010
Record last verified: 2010-12