Drug Interaction Study Between Lumefantrine and Lopinavir/Ritonavir

This study has been completed.
Sponsor:
Collaborator:
University of Liverpool
Information provided by:
Makerere University
ClinicalTrials.gov Identifier:
NCT00619944
First received: February 7, 2008
Last updated: December 3, 2010
Last verified: December 2010
  Purpose

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
HIV Infections
Drug: Lumefantrine - lopinavir/ritonavir drug interaction
Drug: Lumefantrine only arm
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Makerere University:

Primary Outcome Measures:
  • 12 hour pharmacokinetics profile of lumefantrine in HIV-positive patients receiving lopinavir/ritonavir [ Time Frame: 11 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability of lumefantrine/artemether in HIV-positive Ugandan patients receiving lopinavir/ritonavir [ Time Frame: 11 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 32
Study Start Date: February 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00619944

Locations
Uganda
Infectious Diseases Institute, Faculty of Medicine, Makerere University
Kampala, Uganda, 22418
Sponsors and Collaborators
Makerere University
University of Liverpool
Investigators
Principal Investigator: Concepta A. Merry, PhD Trinity College Dublin
  More Information

No publications provided

Responsible Party: Concepta Merry, Infectious Diseases Institute
ClinicalTrials.gov Identifier: NCT00619944     History of Changes
Other Study ID Numbers: CPR 003
Study First Received: February 7, 2008
Last Updated: December 3, 2010
Health Authority: Uganda: National Council for Science and Technology

Keywords provided by Makerere University:
HIV
lumefantrine
lopinavir
Africa
Antimalarials
treatment naïve

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lumefantrine
Lopinavir
Ritonavir
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on October 19, 2014