Background
Methods
Study sites, patients, clinical procedures, and laboratory analysis
Outcomes of the study
Statistical analysis
Results
Trial profile and baseline characteristics
Guwahati | Goa | Mangalore | TOTAL | ||||||
---|---|---|---|---|---|---|---|---|---|
DP | A+M | DP | A+M | DP | A+M | DP | A+M | ||
(N=46) | (N=22) | (N=19) | (N=9) | (N=36) | (N=18) | (N=101) | (N=49) | ||
Gender (n)
| |||||||||
Male : female | 17: 5 | 19: 0 | 8 : 1 | 32 : 4 | 17 : 1 | 78 : 23 | 42 : 7 | ||
Age (years)
| |||||||||
Mean | 29.1 | 31.2 | 25.9 | 26.1 | 28.5 | 27.7 | 28.3 | 29.0 | |
SD | 10.9 | 10.2 | 5.5 | 6.8 | 9.6 | 7.8 | 9.6 | 8.9 | |
Weight (kg)
| |||||||||
Mean | 46.7 | 48.6 | 54.3 | 51.0 | 52.9 | 50.2 | 50.4 | 49.6 | |
SD | 7.8 | 7.9 | 8.8 | 3.3 | 6.6 | 5.5 | 8.2 | 6.4 | |
Race (Asian)
| |||||||||
% | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | |
Presence of fever
| |||||||||
N | 46 | 22 | 17 | 9 | 36 | 18 | 99 | 49 | |
% | 100 | 100 | 89 | 100 | 100 | 100 | 100 | 100 | |
Temperature (°C)
| |||||||||
Mean | 37.9 | 37.9 | 38.9 | 38.6 | 38.9 | 38.8 | 38.4 | 38.4 | |
SD | 0.32 | 0.28 | 0.92 | 0.48 | 0.41 | 0.48 | 0.67 | 0.57 | |
Parasitaemia (μ/L)
| |||||||||
Geometric mean | 5337.7 | 5915.1 | 7547.7 | 6650.2 | 6265.1 | 3279.3 | 6032.0 | 4866.3 | |
Hb (g/L)
| |||||||||
Mean | 98.4 | 91.1 | 124.2 | 113.7 | 105.7 | 116.2 | 105.8 | 105 | |
SD | 25.1 | 21.0 | 22.5 | 19.3 | 21.9 | 23.5 | 25.1 | 24.5 | |
Populations
| |||||||||
Safety/ITT | N | 46 | 22 | 19 | 9 | 36 | 18 | 101 | 49 |
% | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | |
Per Protocol | N | 42 | 22 | 19 | 8 | 19 | 11 | 80 | 41 |
% | 91 | 100 | 100 | 89 | 53 | 61 | 79 | 84 |
Clinical and parasitological outcomes
PCR-corrected | Uncorrected | |||
---|---|---|---|---|
DP | A+M | DP | A+M | |
N (%) | N (%) | N (%) | N (%) | |
95% CI | 95% CI | 95% CI | 95% CI | |
ITT Population
| ||||
Heterogeneity test
| p=0.398a | p=0.800a | ||
Guwahati
| 44 (95.7) | 22 (100) | 44 (95.7) | 22 (100) |
(DP=46, A+M=22) | 89.76; 100 | n.a. | 89.76; 100 | n.a. |
Goa
| 19 (100) | 8 (88.9) | 19 (100) | 7 (77.8) |
(DP=19, A+M=9) | n.a. | 68.4; 100 | n.a. | 50.6; 100 |
Mangalore
| 18 (50.0) | 11 (61.1) | 12 (33.3) | 5 (27.8) |
(DP=36, A+M=18) | 33.7; 66.3 | 38.6; 83.6 | 17.9; 48.7 | 7.1; 48.5 |
Total
| 81 (80.2) | 41 (83.7) | 75 (74.3) | 34 (69.4) |
(DP=101, A+M=49) | 72.4; 88.0 | 73.3; 94.0 | 65.7; 82.8 | 56.5; 82.3 |
95% CI for DP - A+M | −16.4; 9.5 | −10.6; 20.3 | ||
PP population
| ||||
Heterogeneity test
| p=0.978b | p=0.574a | ||
Guwahati
| 42 (100) | 22 (100) | 42 (100) | 22 (100) |
(DP=42, A+M=22) | n.a. | n.a. | n.a. | n.a. |
Goa
| 19 (100) | 8 (100) | 19 (100) | 7 (87.5) |
(DP=19, A+M=8) | n.a. | n.a. | n.a. | 64.6; 100 |
Mangalore
| 18 (94.7) | 11 (100) | 12 (63.2) | 5 (45.5) |
(DP=19, A+M=11) | 84.7; 100 | n.a. | 41.5; 84.9 | 16.0; 74.9 |
Total
| 79 (98.8) | 41 (100) | 73 (91.3) | 34 (82.9) |
(DP=80, A+M=41) | 96.3; 100 | n.a. | 85.1; 97.4 | 71.4; 94.4 |
95% CI for DP - A+M | −3.7; 1.2 | −4.8; 21.4 |
DHA-PQP n/N (%) | AS + MQ n/N (%) | P-value2 | |
---|---|---|---|
Fever prevalence
1
| |||
Day 0 | 99/101 (98.0) | 49/49 (100.0) | 1.000 |
Day 1 | 45/101 (44.6) | 21/49 (42.9) | 0.844 |
Day 2 | 30/100 (30.0) | 14/49 (28.6) | 0.857 |
Day 3 | 23/100 (23.0) | 10/49 (20.4) | 0.720 |
Day 7 | 13/98 (13.3) | 7/46 (15.2) | 0.752 |
Overall (day 0 - day 7) | 99/101 (98.0) | 49/49 (100.0) | 1.000 |
Person-fever-days3 | 260/695 (374.1) | 125/334 (374.3) | 0.994 |
Parasitaemia
| |||
Day 0 | 101/101 (100) | 49/49 (100) | |
Day 1 | 37/101 (36.6) | 15/49 (30.6) | |
Day 2 | 7/101 (6.9) | 4/49 (8.2) | |
Day 3 | 0 | 0 |
DP n/N (%) | A + M n/N (%) | |
---|---|---|
Gametocyte prevalence
1
| ||
Day 7 | 7/98 (7.1) | 0/46 (0.0) |
Day 14 | 5/94 (5.3) | 0/44 (0.0) |
Day 28 | 0/89 (0.0) | 0/42 (0.0) |
Day 42 | 0/85 (0.0) | 0/41 (0.0) |
Day 63 | 0/81 (0.0) | 0/41 (0.0) |
Overall (day 7 - day 63) | 9/98 (9.2) | 0/46 (0.0) |
Gametocyte incidence
2
| ||
Day 7 | 7/98 (7.14) | 0/46 (0.0) |
Day 14 | 2/94 (2.13) | 0/44 (0.0) |
Day 28 | 0/89 (0.0) | 0/42 (0.0) |
Day 42 | 0/85 (0.0) | 0/41 (0.0) |
Day 63 | 0/81 (0.0) | 0/41 (0.0) |
Person-gametocyte-weeks
3
| 18/814 (22.1) | 0/391 (0.0) |
DP | A + M | ||
---|---|---|---|
Day 0
| n | 101 | 49 |
mean (SD) | 105.8 (25.1) | 104.5 (24.5) | |
min/max | 45/177 | 50/158 | |
Day 7
| n | 98 | 46 |
mean (SD) | 103.2 (23.2) | 100.6 (26.2) | |
min/max | 40/170 | 45/170 | |
Day 14
| n | 94 | 43 |
mean (SD) | 108.4 (21.7) | 103.4 (24.0) | |
min/max | 50/170 | 45/145 | |
Day 14 – Day 0
| n | 94 | 43 |
mean (SD) | 2.7 (15.3) | −0.1 (16.0) | |
min/max | −47/41 | −45/51 |
Adverse events
Event (MedDRA Preferred Term)1 | DP n (%) | A + M n (%) |
---|---|---|
At least one AE | 60 (59.4%) | 33 (67.4%) |
Anaemia | 6 (5.9%) | 4 (8.2%) |
Asthenia | 10 (9.9%) | 9 (18.4%) |
Pyrexia | 18 (17.8%) | 10 (20.4%) |
Malaria2 | 5 (5.0%) | 7 (14.3%) |
Eosinophil count increased | 13 (12.9%) | 2 (4.1%) |
Haematocrit decreased | 11 (10.9%) | 5 (10.2%) |
Haemoglobin decreased | 13 (12.9%) | 7 (14.3%) |
Red blood cell count decreased | 11 (10.9%) | 10 (20.4%) |
At least one SAE | 5 (5.0%) | 1 (2.0%) |
At least one drug-related SAE | 4 (4.0%) | 1 (2.0%) |