A Phase 1 interventional study of lopinavir/ritonavir and efavirenz in HIV Infections and Malaria, sponsored by Fran Aweeka. Completed at 1 site in United States. Open to participants aged 21 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2013-06-06.
Sponsored by Fran Aweeka · Phase 1, Interventional, and Treatment
The purpose of the study is to determine in healthy volunteers whether certain anti-HIV medications (lopinavir/ritonavir and efavirenz) affect the drug levels of certain anti-malarial medications (artesunate/ amodiaquine and artemether/ lumefantrine) and vice versa. Since these drugs are degraded using overlapping pathways in the liver, it is predicted that changes in both drug level and overall drug exposure will be observed.
HIV and malaria are two of the most pernicious diseases facing developing countries. Malaria affects 300 to 500 million individuals annually in developing countries and it is estimated that 25.8 million people in Africa live with HIV. Current therapy recommended by the World Health Organization includes the use of artemisinin derivatives, such as artesunate and artemether. To minimize the risk of resistance, these drugs are used in combination with older drugs with longer half-lives including amodiaquine and lumefantrine.
Treatment of malaria is further complicated by the increasing availability of antiretroviral (ARV) medications for HIV in that clinically important drug-drug interactions may occur in co-infected patients. Protease inhibitor (e.g. lopinavir and ritonavir) and non-nucleoside reverse transcriptase (e.g. efavirenz) based treatment commonly affects pharmacokinetic exposure of drugs metabolized by cytochrome P450 (CYP) metabolic pathways.
Artemether is metabolized by the CYP3A4 to active dihydroartemisinin (DHA), while artesunate is hydrolyzed to DHA. Lumefantrine is an active compound that is metabolized by CYP3A4. Amodiaquine is an active "prodrug" that is quickly metabolized to an active metabolite N-desethylamodiaquine (DEAQ) by CYP2C8. In addition, these antimalarial drugs may also affect the metabolism of CYP substrates, such as ARVs.
The primary objective of this study is to investigate the effects of ARV agents (ritonavir/ lopinavir (Kaletra) and efavirenz) on the pharmacokinetics of antimalarial drug combinations [artesunate/ amodiaquine and their active metabolites, and artemether/ lumefantrine (Coartem®) and their active metabolites]. The secondary objective is to investigate the effects of antimalarial drug combinations [artesunate/amodiaquine and artemether/lumefantrine (Coartem®)] on the pharmacokinetics of ARV drugs [lopinavir/ritonavir (Kaletra®) and efavirenz].
If clinically important interactions occur, net effects may include improved or diminished antimalarial activity (as activity is attributed to both the parent drug and the active metabolite(s)) and drug toxicity. The study in HIV negative healthy volunteers will allow rapid assessment of these potential interactions and will provide essential data for optimizing a future clinical study and the use of ARVs and antimalarials for children and adults in Uganda.
Currently the components of the study involving the impact of ARVs on artesunate/amodiaquine are not being pursued (and recruitment for those arms was conducted separately), so there are only two groups in the presently-approved trial: one in which the effects of lopinavir/ritonavir on artemether/lumefantrine are studied and another in which the effects of efavirenz on artemether/lumefantrine are studied.
4,258 studies on the registry are indexed under HIV Infections; 240 are open to participants now.
This study's enrollment of 38 is below the median of 83 across 3,251 interventional studies indexed under HIV Infections.
Browse HIV Infections studies →This is the only study on the registry with Fran Aweeka as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
healthy volunteers assigned to the efavirenz with artemether/lumefantrine intervention
Drug: efavirenz · Drug: artemether/lumefantrine
healthy volunteers assigned to the lopinavir/ritonavir with artemether/lumefantrine intervention
Drug: lopinavir/ritonavir · Drug: artemether/lumefantrine
Two tablets of lopinavir 200mg / ritonavir 50mg orally twice daily with food for 26 days
Also known as: Kaletra
One 600mg tablet orally once daily before bedtime on an empty stomach for 26 days
Also known as: Sustiva
4 tablets of artemether 20mg/lumefantrine 120mg twice daily with food. 2 three-day courses will be administered (with washout in between) during the duration of the trial.
Also known as: Coartem
AUC (zero to infinity) of the antimalarial agent
Time frame: Each 3-day antimalarial treatment course throughout study
This study is completed, as verified in May 2013. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.