Drug Interaction Study Between Antimalarial and Anti-HIV Medications

Study Overview
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Brief Summary
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The purpose of this study is to find out whether taking certain anti-HIV medicines with certain antimalarial medicines affects the amount of the medicines in the blood. The study medicines that will be used are artemether/lumefantrine (antimalarial medication) and lopinavir/ritonavir or efavirenz (anti-HIV medications). Artemether/lumefantrine is not approved by the United States Food and Drug Administration (FDA) but is recommended as standard of care medical treatment for malaria in Africa and Asia. Lopinavir/ritonavir and efavirenz are approved by the FDA. Artemether/lumefantrine and lopinavir/ritonavir or efavirenz may need to be used together to treat children in Africa and Asia. We seek to learn about whether or not the use of these medicines together results in a change in blood levels of any of these medicines. The information obtained from this study will help doctors to provide a better treatment to children and adults with malaria and HIV.

Detailed Description
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The study involves 5 non-consecutive overnight stays and 14 additional outpatient visits at the San Francisco General Hospital Research Center.

Official Title
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Pharmacokinetic Interactions Between Antiretroviral Agents, Lopinavir/Ritonavir and Efavirenz and Antimalarial Drug Combination, Artemether/Lumefantrine

Conditions
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HIV Infections, Malaria

Intervention / Treatment
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* Drug: Lopinavir/Ritonavir, Efavirenz, Artemether/lumefantrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Absence of HIV infection prior to study entry Within 20% (+/-) of ideal body weight and must weigh at least 50kg Healthy subjects without evidence of acute or chronic illnesses, including diabetes, high blood pressure, coronary artery disease, psychiatric illnesses, liver or kidney impairment Exclusion Criteria: Use of illicit drugs or alcohol that could interfere with the completion of the study. Use of any over- the- counter or prescribed drugs unless approved by the principal investigator or study physician. Pregnant or breast- feeding. History of acute or chronic illnesses, such as diabetes, high blood pressure, coronary artery disease, psychiatric illnesses, liver or kidney impairment. Evidence of acute illness. Family history of congenital prolongation of QTc interval or with any conditions known to prolong QTc interval, such as cardiac arrhythmias, bradycardia or severe heart disease History of electrolyte abnormalities.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lopinavir/ritonavir, artemethr/lumefantrine<br>Determination of the antimalarial drug levels artemether/lumefantrine in the absence and in the presence of co-administered antiretrovirals lopinavir and ritonavir. | Drug: Lopinavir/Ritonavir, Efavirenz, Artemether/lumefantrine<br>* participants receive a total of 6 doses of artemether(80mg)/lumefantrine(480mg)for baseline PK evaluation. This is followed by a 26-day course of either efavirenz(600mg) once daily or lopinavir/ritonavir (400mg/100mg) twice daily and additional 6 doses of artemether/lumefantrine to determine the pharmacokinetics of the antimalarial medications in the context of antiretrovirals. The participants undergo at least a 14 day washout period (between the last baseline PK blood draw and the initiation of antiretrovirals)<br>|
| Active Comparator: efavirenz, artemether, lumefantrine<br>Determination of the antimalarial drug levels artemether/lumefantrine in the absence and in the presence of co-administered antiretroviral efavirenz. | Drug: Lopinavir/Ritonavir, Efavirenz, Artemether/lumefantrine<br>* participants receive a total of 6 doses of artemether(80mg)/lumefantrine(480mg)for baseline PK evaluation. This is followed by a 26-day course of either efavirenz(600mg) once daily or lopinavir/ritonavir (400mg/100mg) twice daily and additional 6 doses of artemether/lumefantrine to determine the pharmacokinetics of the antimalarial medications in the context of antiretrovirals. The participants undergo at least a 14 day washout period (between the last baseline PK blood draw and the initiation of antiretrovirals)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic assessment of potential drug-drug interactions of antimalarials and antiretroviral agents. |  | Intensive serial PK sampling of antimalarials conducted on study day 4 (without antiretrovirals) and study day 31 (in the context of antiretrovirals | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy, controls, research, clinical, study, pharmacokinetic, PK, HIV, malaria