Evaluation of Potential Effect of Artemether - Lumefantrine and Malaria Drugs on Auditory Function

Study Overview
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Brief Summary
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To evaluate the potential effects of artemether- lumefantrine on the auditory function

Official Title
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An Open-label, Randomized, Single-center, Parallel Group Study of the Effects of Artemether-lumefantrine (Coartem®) Atovaquone-proguanil (Malarone®) and Artesunate-mefloquine on Auditory Function Following the Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria in Patients 12 Years of Age or Older

Conditions
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Malaria, Falciparum

Intervention / Treatment
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* Drug: Artesunate-mefloquine
* Drug: Atovaquone-proguanil
* Drug: Artemether-lumefantrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria 12 years of age or older Accepts Healthy Volunteers P. falciparum parasitemia between 1,000 and 100,000 parasites/μl History of fever or presence of fever (temperature ≥ 37.5°C) Exclusion Criteria Signs/symptoms of severe/complicated malaria Ingestion of various antimalarial drugs, or antibiotics in the previous 2 weeks to 2 months History of any drug-related hearing impairment Abnormal hearing function at study entry Exposure to sustained loud noises, by self-report, within the past 24 hours Present ear problems Pregnant or lactating (urine test for β-HCG) to be performed on any woman of child bearing age) Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Artemether-lumefantrine (Coartem)<br>Artemether-lumefantrine (Coartem) tablets containing 20 mg artemether and 120 mg lumefantrine twice a day for 3 days, dosage dependent on body weight. | Drug: Artemether-lumefantrine<br> <br> * Other names: Coartem;|
| Active Comparator: Atovaquone-proguanil (Malarone)<br>Atovaquone-proguanil (Malarone) tablets containing 250 mg atovaquone and 100 mg proguanil hydrochloride once daily for 3 days, dosage dependent on body weight. | Drug: Atovaquone-proguanil<br> <br> * Other names: Malarone;|
| Active Comparator: Artesunate-mefloquine<br>Artesunate-mefloquine tablets containing 50 mg artesunate (Plasmotrim) and 250 mg mefloquine (Mephaquin). Artesunate 4 mg/kg/day (for 3 days) and mefloquine 25 mg/kg/day (days 2 and 3) total dose was given once daily dependent upon body weight. | Drug: Artesunate-mefloquine<br> <br> * Other names: Mephaquin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Auditory Abnormalities at Day 7 Assessed by Auditory Brainstem Response (ABR) Wave III Latency Changes on Day 7(a Type of Hearing Test) | To demonstrate the safety of artemether-lumefantrine after 3 days of treatment in patients with acute, uncomplicated falciparum malaria by testing the null hypothesis that the rate of auditory abnormalities is ≥ 15% in the population treated with artemether-lumefantrine as assessed by ABR at Day 7 following initiation of treatment compared with their baseline values. An auditory nerve abnormality is here defined as a greater than 0.30 ms change in Wave III latency from baseline to Day 7. Exact Pearson-Clopper two-sided 95% confidence limits were constructed for all three treatment groups. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Auditory Changes Following 3 Days of Treatment at Days 3, 7, 28, and 42 Days as Assessed by Pure Tone Thresholds Assessments (a Type of Hearing Test) | Audiometric measurements such as pure-tone threshold (air conduction tested at 250 to 8000 HZ) day 3, 7, 28 and 42 following initiation of treatment, including changes from baseline. Pure-tone average (PTA) calculated for each ear by averaging the pure-tone threshold values at 500, 1000, 2000 and 3000 HZ. | Baseline (Day 1), 3, 7, 28 and Day 42 | 
| Relationship Between Changes in Auditory Function and Treatment Groups | ABR Wave III latency (ms) changes from baseline to Day 7 in the three drug exposure groups. | From Baseline to Day 7 | 
| Efficacy of Polymerase Chain Reaction (PCR) Adjusted Malaria Cure Rates of the Three Treatment Regimens at Days 14, 28 and 42 | Percentage of patients with clearance of asexual parasitemia (observed by optical microscopy) within 7 days of initiation of trial treatment without recrudescence within 14, 28 and 42 days respectively after initiation of treatment. Patients with recurrent parasitemia and paired PCR results were classified as either a new infection (different paired genotypes) or a recrudescence (matching paired genotypes). Patients without paired PCR results or ambiguous results were classified as treatment failures. | Days 14, 28 and 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malaria, hearing, co-artemether, auditory, Plasmodium falciparum, marsh fever, Plasmodium infections, remittent fever, paludism, artemether, artemisinins, benflumetol, lumefantrine