Efficacy, Safety and Pharmacokinetics of Artemether-lumefantrine Dispersible Tablet in the Treatment of Malaria in Infants < 5 kg

An Open-label, Single-arm Study to Evaluate the Efficacy, Safety and PK of Artemether-lumefantrine Dispersible Tablet in the Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria in Infants <5 kg Body Weight

The purpose of the study is to obtain efficacy, safety and pharmacokinetic (PK) data following treatment with artemether-lumefantrine dispersible tablet in infants < 5 kg of body weight (BW) with uncomplicated falciparum malaria.

Study Overview

• Status: Completed
• Conditions: Acute Uncomplicated Falciparum Malaria
• Intervention / Treatment: Drug: Artemether-lumefantrine (COA566)

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Benin
  • Cotonou, Benin, 01 BP 107
    • Novartis Investigative Site
  • Cotonou, Benin
    • Novartis Investigative Site
• Burkina Faso
  • Burkina Faso, Burkina Faso, 2208
    • Novartis Investigative Site
  • Ouagadougou, Burkina Faso
    • Novartis Investigative Site
• Congo
  • Kinshasa, Congo
    • Novartis Investigative Site
• Nigeria
  • Calabar, Nigeria
    • Novartis Investigative Site
• Togo
  • Lome, Togo
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Neonates / infants
• Body weight < 5 kg
• In cohort 1, infants aged > 28 days; in cohort 2, neonates of a term age 0 to ≤ 28 days
• Microscopically confirmed diagnosis of acute uncomplicated Plasmodium falciparum malaria or mixed infections with an asexual Plasmodium falciparum parasitaemia of > 1,000 and < 100,000 parasites/µL

Exclusion Criteria:

• Presence of severe malaria (according to World Health Organization definition)
• Presence of the following signs of a critical condition: apnea-bradycardia, sustained bradycardia, tachycardia, desaturation, hypotension, hypothermia; or other severely deteriorated general condition (based on IMCI criteria in sick infants)
• Presence of any clinically significant neurological condition
• Presence of clinically significant abnormality of the hepatic and renal systems
• Patients who sustained a significant blood volume loss (> 3% of calculated blood volume) in the past 30 days
• Patients unable to swallow or whose drinking is impaired
• Family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to be associated with prolongation of the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease
• Disturbances of electrolyte balance (e.g. hypokalaemia or hypomagnesaemia)
• Presence of any age-adjusted clinically or hematologically relevant laboratory and blood chemistry abnormalities
• Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; One Artemether-lumefantrine (COA566) dispersible tablet taken orally twice a day during 3 days. Infants age >28 days.	Drug: Artemether-lumefantrine (COA566); One dispersible tablet taken orally twice a day during 3 days.; Other Names: Artemether-lumefantrine, COA566

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Polymerase Chain Reaction (PCR) Corrected 28 Day Parasitological Cure Rate	Number of participants with clearance of asexual parasites by day 7 after initiating study treatment without recrudescence at day 28, corrected for re-infection by Polymerase Chain Reaction (PCR) assay.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Polymerase Chain Reaction (PCR) Corrected Parasitological Cure Rate at Day 14 and 42	Number of participants with clearance of asexual parasites by day 7 after initiating study treatment without recrudescence at day 14 and day 42, corrected for re-infection by Polymerase Chain Reaction (PCR) assay.	Day 14 and 42
Number of Participants With Parasitological Uncorrected Cure Rate at Day 3, 7, 14, 28 and 42	Number of patients with clearance of asexual parasites at day 3, 7, 14, 28 and 42 after initiating study treatment.	Day 3, 7, 14, 28 and 42
Percent Change of Parasite Count From Baseline at 24 Hours	Percent change of parasite count from baseline at 24 hours	baseline, 24 hours
Number of Participants With Parasitaemia at 48 Hours After Treatment Initiation Greater Than at Baseline	Number of participants with parasite density at 48 hours after treatment initiation greater than parasite density at baseline.	48 hours
Number of Participants With Parasitaemia at 72 Hours After Treatment Initiation Greater Than or Equal to 25 Percent of Count at Baseline	Number of participants with parasite density at 72 hours after treatment initiation greater than or equal to 25 percent of parasite density at baseline.	72 hours
Time to Parasite Clearance (PCT)	Time from first dose until first total and continued disappearance of asexual parasite forms which remains at least a further 48 hours.	Up to 7 days
Time to Fever Clearance (FCT)	Time from first dose to the first time the axillary body temperature decreased below and remained below 37.5° C for at least 48 hours.	Up to 7 days
Time to Gametocyte Clearance (GCT)	Time from first dose until first total and continued disappearance of gametocytes which remains at least a further 48 hours.	Up to 7 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Collaborators: Medicines for Malaria Venture

Publications and helpful links

General Publications

• Tiono AB, Tinto H, Alao MJ, Meremikwu M, Tshefu A, Ogutu B, Ouedraogo A, Lingani M, Cousin M, Lefevre G, Jain JP, Duparc S, Hamed K. Increased systemic exposures of artemether and dihydroartemisinin in infants under 5 kg with uncomplicated Plasmodium falciparum malaria treated with artemether-lumefantrine (Coartem(R)). Malar J. 2015 Apr 15;14:157. doi: 10.1186/s12936-015-0682-7.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: June 12, 2012
• First Submitted That Met QC Criteria: June 13, 2012
• First Posted (Estimate): June 14, 2012

Study Record Updates

• Last Update Posted (Estimate): June 17, 2015
• Last Update Submitted That Met QC Criteria: June 1, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: malaria; infant; neonate; P. falciparum; plasmodium
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination
• Other Study ID Numbers: CCOA566B2306; 2011-005852-33; 2011-005858-33 (Other Identifier: Eudra CT)