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

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01619878

Enrollment

Registered

2012-06-14

Start date

2012-10-31

Completion date

2014-07-31

Last updated

2015-06-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Uncomplicated Falciparum Malaria

Keywords

plasmodium, P. falciparum, malaria, infant, neonate

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.

Interventions

DRUGArtemether-lumefantrine (COA566)

One dispersible tablet taken orally twice a day during 3 days.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Healthy volunteers

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/

Design outcomes

Primary

Measure	Time frame	Description
Polymerase Chain Reaction (PCR) Corrected 28 Day Parasitological Cure Rate	28 days	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

Measure	Time frame	Description
Number of Participants With Parasitological Uncorrected Cure Rate at Day 3, 7, 14, 28 and 42	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	baseline, 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	48 hours	Number of participants with parasite density at 48 hours after treatment initiation greater than parasite density at baseline.
Polymerase Chain Reaction (PCR) Corrected Parasitological Cure Rate at Day 14 and 42	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.
Time to Parasite Clearance (PCT)	Up to 7 days	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)	Up to 7 days	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)	Up to 7 days	Time from first dose until first total and continued disappearance of gametocytes which remains at least a further 48 hours.
Number of Participants With Parasitaemia at 72 Hours After Treatment Initiation Greater Than or Equal to 25 Percent of Count at Baseline	72 hours	Number of participants with parasite density at 72 hours after treatment initiation greater than or equal to 25 percent of parasite density at baseline.

Countries

Benin, Burkina Faso, Nigeria, Republic of the Congo, Togo

Participant flow

Recruitment details

The participant that did not complete in the 6 week follow-up phase was also included in Follow-up at 12 Months of Age and was lost to follow-up

Participants by arm

Arm	Count
Cohort 1 One Artemether-lumefantrine (COA566) dispersible tablet taken orally twice a day during 3 days. Infants age \>28 days.	20
Total	20

Withdrawals & dropouts

Period	Reason	FG000
6 Week Follow-up Phase	Adverse Event	1
Follow-up at 12 Months of Age	Death	2
Follow-up at 12 Months of Age	Lost to Follow-up	1

Baseline characteristics

Characteristic	Cohort 1
Age, Continuous	99.1 days STANDARD_DEVIATION 51.75
Sex: Female, Male Female	10 Participants
Sex: Female, Male Male	10 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	16 / 20
serious Total, serious adverse events	3 / 20

Outcome results

Primary

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.

Time frame: 28 days