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

Sponsor:	Novartis
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00444106

Purpose

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

Condition	Intervention	Phase
Malaria Falciparum	Drug: Artesunate-mefloquine Drug: Atovaquone-proguanil Drug: Artemether-lumefantrine	Phase IV

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

Resource links provided by NLM:

MedlinePlus related topics: Fever Malaria

Drug Information available for: Mefloquine hydrochloride Mefloquine Artemether Benflumetol Artesunate Atovaquone Co-artemether Malarone Chloroguanide

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

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) [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
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.

Secondary Outcome Measures:

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) [ Time Frame: Baseline (Day 1), 3, 7, 28 and Day 42 ] [ Designated as safety issue: Yes ]
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.
Relationship Between Changes in Auditory Function and Treatment Groups [ Time Frame: From Baseline to Day 7 ] [ Designated as safety issue: Yes ]
ABR Wave III latency (ms) changes from baseline to Day 7 in the three drug exposure groups.
Efficacy of Polymerase Chain Reaction (PCR) Adjusted Malaria Cure Rates of the Three Treatment Regimens at Days 14, 28 and 42 [ Time Frame: Days 14, 28 and 42 ] [ Designated as safety issue: No ]
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.

Enrollment:	265
Study Start Date:	May 2007
Study Completion Date:	November 2008
Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Artemether-lumefantrine (Coartem) 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 Other Name: Coartem
Active Comparator: Atovaquone-proguanil (Malarone) 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 Other Name: Malarone
Active Comparator: Artesunate-mefloquine 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 Other Names: Plasmotrim Mephaquin

Eligibility

Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00444106

Locations

Colombia
Novartis Investigational Site
Tumaco, Colombia

Sponsors and Collaborators

Novartis

Investigators

Study Director:

Novartis

More Information

No publications provided

Responsible Party:	Novartis
ClinicalTrials.gov Identifier:	NCT00444106 History of Changes
Other Study ID Numbers:	CCOA566A2417
Study First Received:	March 6, 2007
Results First Received:	December 8, 2010
Last Updated:	April 1, 2011
Health Authority:	Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos

Keywords provided by Novartis:

Malaria
hearing
co-artemether
auditory
Plasmodium falciparum
marsh fever
Plasmodium infections

remittent fever
paludism
artemether
artemisinins
benflumetol
lumefantrine

Additional relevant MeSH terms:

Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Proguanil
Mefloquine
Artemether
Artemisinins
Artesunate
Atovaquone
Lumefantrine
Malarone
Artemether-lumefantrine combination
Antimalarials

Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Coccidiostats
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics
Amebicides
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012