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

Phase 4CompletedNCT00444106

Novartis265 enrolled

Overview

To evaluate the potential effects of artemether- lumefantrine on the auditory function

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

265

Conditions

Malaria Falciparum

Interventions

Artesunate-mefloquineDRUG

Atovaquone-proguanilDRUG

Artemether-lumefantrineDRUG

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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.

Locations (1)

Novartis Investigational Site

Tumaco, Colombia

Outcomes

Primary Outcomes

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.

Time frame: 7 days

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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