Malaria, HIV
Conditions
Keywords
malaria, HIV, AIDS, nevirapine, lumefantrine, artemether, drug interaction, pharmacokinetics
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.
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
DRUGArtemether/ lumefantrine
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
Sponsors
London School of Hygiene and Tropical Medicine
University of Cape Town
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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).
Exclusion criteria
* 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. * Pharmacokinetic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Lumefantrine plasma concentration | day 7 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
South Africa
Outcome results
None listed