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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00444106
First received: March 6, 2007
Last updated: April 1, 2011
Last verified: April 2011
  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 4

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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 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 July 22, 2014