Trial Outcomes & Findings for Pharmacokinetics, Safety, Tolerability and Efficacy of a New Artemether-lumefantrine Dispersible Tablet in Infants and Neonates <5 kg Body Weight With Acute Uncomplicated Plasmodium Falciparum Malaria (NCT NCT04300309)

Participants took part in 3 investigative sites in 2 countries.

The Screening procedures began once the study informed consent had been obtained. Screening was performed within 12 hours before the first study drug administration.

Pharmacokinetics, Safety, Tolerability and Efficacy of a New Artemether-lumefantrine Dispersible Tablet in Infants and Neonates <5 kg Body Weight With Acute Uncomplicated Plasmodium Falciparum Malaria

Artemether Cmax represents the highest concentration between the concentrations at 1 hour and 2 hours after first dose. Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on artemether plasma concentrations.

Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on lumefantrine plasma concentrations. Dosing times were 0, 8, 24, 36, 48 and 60 hours.

Lumefantrine Cmax represents the highest concentration among four sampling time points after last dose. Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on lumefantrine plasma concentrations. Dosing times were 0, 8, 24, 36, 48 and 60 hours.

Dihydroartemisinin (DHA) is an active metabolite of artemether. DHA Cmax represents the highest concentration between the concentrations at 1 hour and 2 hours after first dose. Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on DHA plasma concentrations.

PCT is defined as time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 48 hours. PCT is based on uncorrected parasite counts. Patients who received rescue medication before parasite clearance were censored at the first use of rescue medication. Patients without parasite clearance were censored at the time of last parasite assessment. PCT was calculated using the Kaplan-Meier method.

FCT is defined as time from the first dose until the first time the axillary body temperature decreased below and remained below 37.5°C axillary or 38.0°C oral/tympanic/rectal for at least a further 24 hours. Patients who received rescue medication before fever clearance were censored at the first use of rescue medication. Patients without fever clearance were censored at the time of last parasite assessment. FCT was calculated using the Kaplan-Meier method.

PCR-corrected ACPR, defined as the absence of parasitemia, was evaluated on Days 15, 29 and 43. Microscopic species identification was confirmed and determined by polymerase chain reaction (PCR) genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR-corrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 15, 29 or 43 irrespective of axillary temperature unless the presence of parasitemia after 7 days was due to reinfection based on PCR. A presence of parasitemia after 7 days of treatment initiation was considered as a reinfection only if the parasitemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR.

PCR-corrected ACPR, defined as the absence of parasitemia, was evaluated on Days 15, 29 and 43. Microscopic species identification was confirmed and determined by polymerase chain reaction (PCR) genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR-corrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 15, 29 or 43 irrespective of axillary temperature unless the presence of parasitemia after 7 days was due to reinfection based on PCR. A presence of parasitemia after 7 days of treatment initiation was considered as a reinfection only if the parasitemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR.

PCR-uncorrected ACPR, defined as the absence of parasitemia, was evaluated on Days 8, 15, 29 and 43. A participant was considered as PCR-uncorrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 8, 15, 29 or 43 irrespective of axillary temperature.

Recrudescence is defined as appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at baseline. Recrudescence had to be confirmed by PCR analysis.

New infection is defined as appearance of asexual parasites after clearance of initial infection with a genotype different from those parasites present at baseline. New infection had to be confirmed by PCR analysis.

Number of participants with adverse events (any AEs regardless of seriousness), including changes in laboratory results qualifying and reported as adverse events.

Number of participants with serious adverse events (SAEs), including changes in laboratory results qualifying and reported as serious adverse events.