Baseline characteristics of the healthy male volunteers. For the continuous variables we show the median (range). Of the 27 volunteers, 13 participated in both sub-studies. †also known as Quing Yan (Minucci et al., 2012).‡haemoglobin typing done by electrophoresis in part 1 only. ∗see definition in Methods.

Ascending dose study in 23 male hemizygote G6PD deficient healthy volunteers included in the primary analysis. Colours from blue to red are in order of increasing day 10 total cumulative primaquine dose as shown in panel a (cumulative primaquine doses over time). Panels b & c show the absolute haemoglobin values and reticulocyte counts over time; panel d shows the relative change from baseline in haemoglobin over time. The thick black lines in panels b-d show the daily median values.

Haemolytic effect of 45 mg single primaquine dose in 16 male hemizygote G6PD deficient healthy volunteers. Colours from blue to red are in order of increasing mg/kg dose. Panel a: absolute haemoglobin values; panel b: reticulocyte counts; panel c: relative change in haemoglobin from baseline. The thick black lines in panels a-c show the daily median values.

Comparing the haemolytic effect of ascending dose primaquine regimens (dark blue triangles) and the single 45 mg primaquine dose (pink circles). The top panels show the relationship between the total cumulative dose of primaquine given to each subject in each study (x-axis) and the absolute fall in haemoglobin concentration (left panel) or the relative fall (right panel). Subjects who participated in both parts are joined by the light grey dashed lines. The horizontal dashed lines show the median falls by sub-study. The bottom panels show the daily observed changes in haemoglobin (left: Part 1; right: Part 2), the red line shows the daily median change.

Haemolysis dose-response relationships (left column: Part 1; right column: Part 2). The dose exposure summary in Part 1 is the day 10 cumulative primaquine dose (n=23); for Part 2 it is the mg/kg single dose (n=16). Hb: haemoglobin.

Relationship between primaquine dose (Part 1: day 10 cumulative mg/kg dose; Part 2: mg/kg single dose) and total plasma bilirubin (panels a and c) and LDH concentrations (panels b and d). The top row show the normalised data; the bottom row the dose-response relationship with the maximum normalised increases.

Changes in blood methaemoglobin concentration. Top row: individual data (left: Part 1; right: Part 2) with the daily mean value shown by the thick black line. Bottom row: relationship between dose (left: Part 1 summarised by the day 10 total dose; right: Part 2 summarised by the mg/kg dose) and peak observed blood methaemoglobin (%).