Efficacy, Safety and Pharmacokinetics of Artemether-lumefantrine Dispersible Tablet in the Treatment of Malaria in Infants < 5 kg
Primary Purpose
Acute Uncomplicated Falciparum Malaria
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Artemether-lumefantrine (COA566)
Sponsored by
About this trial
This is an interventional treatment trial for Acute Uncomplicated Falciparum Malaria focused on measuring plasmodium, P. falciparum, malaria, infant, neonate
Eligibility Criteria
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.
Sites / Locations
- Novartis Investigative Site
- Novartis investigative site
- Novartis Investigative Site
- Novartis investigative site
- Novartis investigative site
- Novartis investigative site
- Novartis investigative site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cohort 1
Arm Description
One Artemether-lumefantrine (COA566) dispersible tablet taken orally twice a day during 3 days. Infants age >28 days.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Percent Change of Parasite Count From Baseline at 24 Hours
Percent change of parasite count from baseline at 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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01619878
First Posted
June 12, 2012
Last Updated
June 1, 2015
Sponsor
Novartis Pharmaceuticals
Collaborators
Medicines for Malaria Venture
1. Study Identification
Unique Protocol Identification Number
NCT01619878
Brief Title
Efficacy, Safety and Pharmacokinetics of Artemether-lumefantrine Dispersible Tablet in the Treatment of Malaria in Infants < 5 kg
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
Collaborators
Medicines for Malaria Venture
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Uncomplicated Falciparum Malaria
Keywords
plasmodium, P. falciparum, malaria, infant, neonate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
One Artemether-lumefantrine (COA566) dispersible tablet taken orally twice a day during 3 days.
Infants age >28 days.
Intervention Type
Drug
Intervention Name(s)
Artemether-lumefantrine (COA566)
Other Intervention Name(s)
Artemether-lumefantrine, COA566
Intervention Description
One dispersible tablet taken orally twice a day during 3 days.
Primary Outcome Measure Information:
Title
Polymerase Chain Reaction (PCR) Corrected 28 Day Parasitological Cure Rate
Description
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.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Polymerase Chain Reaction (PCR) Corrected Parasitological Cure Rate at Day 14 and 42
Description
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.
Time Frame
Day 14 and 42
Title
Number of Participants With Parasitological Uncorrected Cure Rate at Day 3, 7, 14, 28 and 42
Description
Number of patients with clearance of asexual parasites at day 3, 7, 14, 28 and 42 after initiating study treatment.
Time Frame
Day 3, 7, 14, 28 and 42
Title
Percent Change of Parasite Count From Baseline at 24 Hours
Description
Percent change of parasite count from baseline at 24 hours
Time Frame
baseline, 24 hours
Title
Number of Participants With Parasitaemia at 48 Hours After Treatment Initiation Greater Than at Baseline
Description
Number of participants with parasite density at 48 hours after treatment initiation greater than parasite density at baseline.
Time Frame
48 hours
Title
Number of Participants With Parasitaemia at 72 Hours After Treatment Initiation Greater Than or Equal to 25 Percent of Count at Baseline
Description
Number of participants with parasite density at 72 hours after treatment initiation greater than or equal to 25 percent of parasite density at baseline.
Time Frame
72 hours
Title
Time to Parasite Clearance (PCT)
Description
Time from first dose until first total and continued disappearance of asexual parasite forms which remains at least a further 48 hours.
Time Frame
Up to 7 days
Title
Time to Fever Clearance (FCT)
Description
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.
Time Frame
Up to 7 days
Title
Time to Gametocyte Clearance (GCT)
Description
Time from first dose until first total and continued disappearance of gametocytes which remains at least a further 48 hours.
Time Frame
Up to 7 days
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Cotonou
ZIP/Postal Code
01 BP 107
Country
Benin
Facility Name
Novartis investigative site
City
Cotonou
Country
Benin
Facility Name
Novartis Investigative Site
City
Burkina Faso
ZIP/Postal Code
2208
Country
Burkina Faso
Facility Name
Novartis investigative site
City
Ouagadougou
Country
Burkina Faso
Facility Name
Novartis investigative site
City
Kinshasa
Country
Congo
Facility Name
Novartis investigative site
City
Calabar
Country
Nigeria
Facility Name
Novartis investigative site
City
Lome
Country
Togo
12. IPD Sharing Statement
Citations:
PubMed Identifier
25886021
Citation
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.
Results Reference
derived
Learn more about this trial
Efficacy, Safety and Pharmacokinetics of Artemether-lumefantrine Dispersible Tablet in the Treatment of Malaria in Infants < 5 kg
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