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 and c show the absolute haemoglobin …
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 …
Panels a-b 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 (panel a) or the …
Three pre-specified outcome variables are shown: the maximum absolute reduction in haemoglobin (panels a & b); the maximum relative reduction (panels c & d); and the mean daily reduction between …
The top rows show the normalised data; the bottom rows the dose-response relationship with the maximum normalised increases.
Top row: individual data (panel a: Part 1; panel b: Part 2) with the daily mean value shown by the thick black line. Bottom row: relationship between dose (panel c: Part 1 summarised by the day 10 …
These pre-specified rules were for guidance only and were not binding as participant safety was the primary concern.
Each cycle was between 3 and 5 days, and doses were increased across the successive cycles. Each subject progressed to the next cycle (i.e. higher dose) only if they had a haemoglobin >70% of their …
The top panels show the dose of primaquine given each day; the bottom panels show the observed haemoglobin measurements (left) and reticulocyte counts (right). Black circles: haemocue and manual …
The subject‘s maximum Hillmen score on days 4–9 varied between 2 and 3 .
Both received very similar ascending dose regimens which are shown in the top panels (mg/kg primaquine daily dose); the middle panels show the observed haemoglobin measurements; the bottom panels …
Black: Part 1; red: Part 2. Each subject has two datapoints corresponding to when the total bilirubin was measured (days 5 and 10 for Part 1; days 3 and 7 for Part 2). The relationship is …
Colours correspond to the day 10 cumulative dose (as in Figure 1 in main text). The numbers in the top panels highlight the data from subjects 7, 11, and 14 who had substantial raises in AST and ALT.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
Blue shows the manual reticulocyte readings and haemocue value; red shows the complete blood count (CBC) values.
The haemocue gave systematically higher haemoglobin concentrations relative to the CBC for low haemoglobin concentrations (about 0.5 g/dL higher at a haemoglobin of 10 g/dL).
For the continuous variables we show the median (range). Of the 27 volunteers, 13 participated in both sub-studies.
Part 1 - Ascending dose | Part 2 - Single 45 mg dose | Overall | |
---|---|---|---|
n | 24 | 16 | 27 |
Age (years) | 32 (18–55) | 34 (20–58) | 32 (18–58) |
Weight (kg) | 64 (46–86) | 64 (52–86) | 64 (46–86) |
G6PD genotype | |||
Viangchan (871G>A) | 12 | 6 | 12 |
Mahidol (487G>A) | 4 | 2 | 4 |
Canton (1376G>T) | 4 | 3 | 5 |
Aures (143T>C) | 1 | 1 | 1 |
Chinese-4 (392G>T)† | 1 | 0 | 1 |
Orissa (131C>G) | 1 | 1 | 1 |
Union (1360C>T) | 1 | 2 | 2 |
Kaiping (1388G>A) | 0 | 1 | 1 |
G6PD enzyme activity (U/g Hb) | 0.15 (0–1.9) | ||
Haemoglobin (g/dL) | 14.3 (11.8–15.8) | 14.0 (12.3–15.9) | |
Red cell count (×1012 per L) | 4.9 (4.2–6.0) | 5.1 (3.9–5.9) | |
Reticulocyte count (%) | 2.4 (1.1–4.0) | 2.4 (1.0–2.9) | |
Platelet count (×1000 per µL) | 285 (190–424) | 289 (174–412) | |
Total white blood cell count (×1000 per µL) | 6.6 (4.8–9.3) | 6.6 (5.2–8.4) | |
Methaemoglobin (%) | 0.5 (0–1.5) | 0.7 (0–1.4) | |
AST (IU/L) | 23 (15–60) | 21 (14–36) | |
ALT (IU/L) | 26 (10–85) | 22 (11–47) | |
Creatinine (mg/dL) | 0.9 (0.8–1.1) | 1.0 (0.7–1.1) | |
Total bilirubin (mg/dL) | 0.6 (0.3–1.6) | 0.7 (0.3–1.3) | |
Haptoglobin (g/L) | 1.1 (0.5–1.7) | 1.1 (0.5–1.7) | |
CYP2D6 genotypes | |||
*10/*10 | 6 | 4 | 8 |
*2/*10 | 7 | 4 | 7 |
*1/*10 | 6 | 4 | 7 |
*1/*2 | 3 | 3 | 3 |
*1/*1 | 2 | 1 | 2 |
Haemoglobin E trait‡ | 7 | 4 | 7 |
Presumptive alpha-thalassaemia trait* | 5 | 5 | 7 |
See definition in Methods.
Also known as Quing Yan (Minucci et al., 2012).
Haemoglobin typing done by electrophoresis in Part 1 only.