A Pharmacokinetics, Safety and Efficacy Study of Tafenoquine (TQ) in Pediatric Subjects With Plasmodium Vivax (P. Vivax) Malaria

Blood samples were collected at indicated time points for pharmacokinetic analysis of tafenoquine. Pharmacokinetic parameters were determined using standard non-compartmental methods. AUC(0-infinity) of tafenoquine was evaluated for participants aged >=2 years to <16 years (weighing >=5 kg). Pharmacokinetic (PK) population consisted of all participants with at least one PK sample taken at Days 3, 15, 29 and 60, with accurate dosing and sample time histories.

Number of participants experiencing gastrointestinal adverse events including vomiting, abdominal pain, diarrhea, gastrointestinal disorder, epigastric discomfort and nausea were assessed. Number of participants with gastrointestinal adverse events for each treatment group have been presented. Safety Population consisted of all participants who received at least one dose of study medication (tafenoquine).

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is known to be a risk factor for hemolysis in participants treated with 8-aminoquinolines. Blood samples were collected for the evaluation of hemoglobin levels. Hemoglobin decrease of >=30 percent (%) of >30 grams per liter (g/L) from Baseline; or, an overall drop in hemoglobin below 60.0 g/L in the first 15 days of the study were considered as protocol defined serious adverse events (SAEs). Number of participants with hemoglobin decline from Baseline over first 10 days have been presented. Baseline was defined as the latest pre-tafenoquine dose assessment on Day 1.

An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/ birth defect, other situations and is associated with liver injury.

Blood samples were collected for analysis of eosinophils, lymphocytes, platelets and reticulocytes. PCI ranges were >1.5*10^9 (high) cells per liter (cells/L) for eosinophils, <0.5*10^9 cells/L (low) or >4*10^9 cells/L (high) for lymphocytes, <50*10^9 cells/L (low) for platelet count and >1*upper limit of normal (ULN) 10^12 cells/L (high) for reticulocyte count. Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Baseline value is the latest pre-tafenoquine dose assessment on Day 1.

Blood samples were collected for analysis of clinical chemistry parameters. PCI ranges were >3*ULN international units per liter (IU/L) (alanine aminotransferase [ALT]), >2.5*ULN IU/L (alkaline phosphatase), >3*ULN IU/L (aspartate aminotransferase [AST]), >1.5*ULN micromoles/L (mcmol/L) (bilirubin), >5*ULN IU/L (creatine kinase [CK]), 3*ULN mcmol/L (creatinine), >1.5*ULN mcmol/L (indirect bilirubin), and >11.067 millimoles/L (urea). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Participants were counted twice if participant has values that changed "To Low and To High", so the percentages may not add to 100%. Baseline value is the latest pre-Tafenoquine dose assessment on Day 1.

Relapse is defined as positive blood smear with or without vivax malaria symptoms. A participant was considered to have demonstrated relapse-free efficacy if: a) Participant is slide positive for Plasmodium vivax (P. vivax) at Baseline. b) Participant showed initial clearance of P. vivax parasitemia defined as a negative slide at or before the Day 29 visit. c) Participant is not slide-positive for P. vivax at any assessment. d) Participant did not take a concomitant medication with anti-malarial activity at any point between Study Day 1 and their last parasite assessment. e) Participant is parasite-free at 4 months defined as a negative asexual P. vivax parasite slide at the first parasite assessment performed during study. Microbiologic-Intent-To-Treat (mITT) Population consisted of all participants who received a dose of study treatment (tafenoquine) and had microscopically-confirmed vivax parasitemia at Baseline.

Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of tafenoquine.