Efficacy, Safety, and PK of M5717 in Combination With Pyronaridine as Chemoprevention in Adults and Adolescents With Asymptomatic Plasmodium Falciparum Infection (CAPTURE-2)

The time (in days) to first recorded parasitemia (parasite count >0) since the first negative blood smear (parasite count of 0) after treatment (followed at least by 1 subsequent visit with a negative blood film), i.e. the time without a positive blood smear. Median time and 95% CI was estimated using the Kaplan Meier method for each cohort.

Percentage of participants with a positive blood smear (parasitemia) was reported. Parasitemia is the presence of parasites in blood (parasite count >0).

Percentage of participants with polymerase chain reaction (PCR)-adjusted Parasitemia (Thick Smear/Microscopy, after Adjustment for Parasitemia due to new Infections as determined by Genotyping using PCR Techniques) was reported.

Percentage of participants with polymerase chain reaction (PCR)-adjusted Parasitemia (Thick Smear/Microscopy, after Adjustment for Parasitemia due to Recrudescence as determined by Genotyping using PCR Techniques) was reported.

Parasite clearance time defined as time from dosing to the first negative (no parasites) blood film (microscopy). Median parasite clearance time was estimated by Kaplan-Meier method

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with study drug which does not necessarily had a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE was defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs. Treatment-related TEAEs: reasonably related to study intervention.

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated blood concentration at the last sampling time point at which the measured blood concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured blood concentrations of the terminal log-linear phase.

AUC from time zero to 24 hours post dose, calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval.

Area under the blood concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from blood, CL= Dose/AUC0-inf.

Cmax was obtained directly from the concentration versus time curve.

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z.

Time to reach the maximum blood concentration (Tmax) was obtained directly from the concentration versus time curve.

The Vz/f was defined as the theoretical volume in which the total amount of required to uniformly distribute to produce the desired plasma concentration. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz/f=Dose/AUC(0-inf) multiply Lambda(z).