Artemether/Lumefantrine and Nevirapine Interaction Study in HIV-infected Adults
Pharmacokinetic Interaction Between the Antimalarial Combination Artemether/Lumefantrine and Combination Antiretroviral Therapy Including Nevirapine in HIV-infected Adults
2 other identifiers
interventional
36
1 country
1
Brief Summary
Despite the clinical significance of potential interactions between antimalarials and antiretrovirals, no drug interaction studies have been published and there is an urgent need to address this gap in current knowledge. This study aims to assess the drug interaction between the antimalarial Artemether/Lumefantrine used for management of uncomplicated malaria and Nevirapine-based antiretroviral therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_4
Started Oct 2008
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2008
CompletedFirst Submitted
Initial submission to the registry
November 13, 2008
CompletedFirst Posted
Study publicly available on registry
November 14, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2009
CompletedJune 28, 2010
June 1, 2010
10 months
November 13, 2008
June 25, 2010
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Lumefantrine plasma concentration
day 7
Secondary Outcomes (1)
Point estimates and 90% confidence intervals for the mean ratios of the lumefantrine, artemether and DHA log-transformed Cmax, AUC0-t, AUC0 ∞ , t½,z, tmax and MRT with/without NVP
21 days
Study Arms (2)
Antiretroviral-naive
OTHERAntiretroviral-naive included as control group
Nevirapine-based antiretroviral therapy
ACTIVE COMPARATORNevirapine-based antiretroviral therapy
Interventions
Coartem (fixed dose Artemether20mg /Lumefantrine 120mg) Dose: 4 tablets(80mg/480mg) twice daily for 3 days at 0,8,24,36,48 and 60 hours
Coartem (fixed dose Artemether20mg /Lumefantrine 120mg) Dose: 4 tablets(80mg/480mg) twice daily for 3 days at 0,8,24,36,48 and 60 hours
Eligibility Criteria
You may qualify if:
- Informed and given ample time and opportunity to think about participation and willing and able to comprehend and comply with all trial requirements. The participant has given written informed consent to participate in the study and to abide by study restrictions.
- Male or female subjects older than 18 years of age.
- HIV-infected as documented by positive HIV-antibody test and confirmed by Western blot.
- Body weight more than 35kg with a body mass index (BMI) ranging between 18.5 to 30kg/m2 inclusive (See Appendix 16.2).
- Karnofsky score above 70 (See Appendix 16.5).
- CD4 count ≥ 200 cells/mm3
- Patients on NVP-based cART at stable doses without significant toxicity for at least 6 weeks at screening (Group 2 only).
You may not qualify if:
- Patients diagnosed with Plasmodium falciparum malaria
- Contraindications to artemether/lumefantrine:
- Hypersensitivity to the artemether, lumefantrine or to any of the excipients of Coartem®.
- Patients with severe malaria according to WHO definition.
- Pregnant (as confirmed by an HCG test performed at screening) or breast-feeding female.
- Patients with a family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to prolong the QTc interval such as patients with a history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease.
- Patients with known disturbances of electrolyte balance e.g. hypokalaemia or hypomagnesaemia.
- Patients taking any drug which is metabolised by the cytochrome enzyme CYP2D6 (e.g. flecainide, metoprolol, imipramine, amitriptyline, clomipramine).
- Patients taking drugs that are known to prolong the QTc interval such as antiarrhythmics of classes IA and III, neuroleptics, antidepressive agents, certain antibiotics including some agents of the following classes: macrolides, fluoroquinolones, imidazole, and triazole antifungal agents, certain non-sedating antihistaminics (terfenadine, astemizole), cisapride.
- Contraindication to nevirapine:
- Hypersensitivity to nevirapine or any of the excipients of Aspen Nevirapine®.
- Severe hepatic dysfunction: Child-Pugh class B or C and in endstage renal failure in patients not on haemodialysis.
- Aspartate transaminase (AST) or alanine aminotransferase (ALT) \> 5 x upper limit of normal (ULN).
- History of severe rash, rash accompanied by constitutional symptoms; hypersensitivity syndrome, or clinical hepatitis due to nevirapine.
- Haemoglobin below 8.5g/dL for female and 9.5g/dL for male subjects.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Groote Schuur Hospital, Research ward
Cape Town, South Africa
Related Publications (1)
Kredo T, Mauff K, Van der Walt JS, Wiesner L, Maartens G, Cohen K, Smith P, Barnes KI. Interaction between artemether-lumefantrine and nevirapine-based antiretroviral therapy in HIV-1-infected patients. Antimicrob Agents Chemother. 2011 Dec;55(12):5616-23. doi: 10.1128/AAC.05265-11. Epub 2011 Sep 26.
PMID: 21947399DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Karen Barnes, MD
University of Cape Town
- STUDY DIRECTOR
Tamara Kredo, MD
University of Cape Town
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
November 13, 2008
First Posted
November 14, 2008
Study Start
October 1, 2008
Primary Completion
August 1, 2009
Study Completion
December 1, 2009
Last Updated
June 28, 2010
Record last verified: 2010-06