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

Malaria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00444106
• Other study ID #: CCOA566A2417
• Status: Completed
• Phase: Phase 4
• First received: March 6, 2007
• Last updated: April 1, 2011
• Start date: May 2007
• Est. completion date: November 2008

Study information

• Verified date: April 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 265
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Gender: Both
• Age group: 12 Years and older

Eligibility

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 ß-HCG) to be performed on any woman of child bearing age)

Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Falciparum
• Malaria

Intervention

Drug:
• Artesunate-mefloquine

• Atovaquone-proguanil

• Artemether-lumefantrine

Locations

Country	Name	City	State
Colombia	Novartis Investigational Site	Tumaco

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

Colombia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No