Trial Outcomes & Findings for Phase II Efficacy Study of Artefenomel & Piperaquine in Adults & Children With P. Falciparum Malaria. (NCT NCT02083380)
NCT ID: NCT02083380
Last Updated: 2017-03-10
Results Overview
Polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification. Per protocol population (PP). 95% Clopper-Pearson 2-sided Confidence Interval (CI) constructed around the single binomial proportion per treatment arm and total.
COMPLETED
PHASE2/PHASE3
448 participants
Day 28
2017-03-10
Participant Flow
Randomized double blind study. Conduct was July 2014-August 2015 in Africa (Benin, Burkina Faso, Democratic Republic of Congo, Gabon, Mozambique and Uganda) and Vietnam. Following informed consent patients were recruited to the study. Patients below the age to give legal Informed Consent were consented according local customs / legal requirements.
Patients were assigned a screening number and underwent screening procedures to assess eligibility. Eligible patients were randomized through an Interactive web-response system and followed for efficacy and safety up to 42 days post dose and 63 days at selected centers. Patients were consented separately to remain in the study up to Day 63.
Participant milestones
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Overall Study
STARTED
|
148
|
151
|
149
|
|
Overall Study
COMPLETED
|
57
|
56
|
65
|
|
Overall Study
NOT COMPLETED
|
91
|
95
|
84
|
Reasons for withdrawal
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
Artefenomel 800mg: Piperaquine phosphate 640mg loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Overall Study
Lack of Efficacy
|
68
|
79
|
64
|
|
Overall Study
Withdrawal by Subject
|
9
|
3
|
7
|
|
Overall Study
Physician Decision
|
1
|
6
|
3
|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
5
|
3
|
3
|
|
Overall Study
Other
|
8
|
4
|
6
|
Baseline Characteristics
Phase II Efficacy Study of Artefenomel & Piperaquine in Adults & Children With P. Falciparum Malaria.
Baseline characteristics by cohort
| Measure |
A) Artefenomel 800mg: PQP 640mg
n=143 Participants
Artefenomel 800mg: Piperaquine 640mg
|
B) Artefenomel 800mg: PQP 960mg
n=148 Participants
Artefenomel 800mg: Piperaquine 960mg
|
C) Artefenomel 800mg: PQP 1440mg
n=146 Participants
Artefenomel 800mg: Piperaquine 1440mg
|
Total
n=437 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
> 15 years
|
41 participants
n=93 Participants
|
42 participants
n=4 Participants
|
41 participants
n=27 Participants
|
124 participants
n=483 Participants
|
|
Age, Customized
> 5 to <= 15 years
|
8 participants
n=93 Participants
|
8 participants
n=4 Participants
|
9 participants
n=27 Participants
|
25 participants
n=483 Participants
|
|
Age, Customized
> 2 to <= 5 years
|
69 participants
n=93 Participants
|
72 participants
n=4 Participants
|
70 participants
n=27 Participants
|
211 participants
n=483 Participants
|
|
Age, Customized
>= 0.5 to <= 2 years
|
25 participants
n=93 Participants
|
26 participants
n=4 Participants
|
26 participants
n=27 Participants
|
77 participants
n=483 Participants
|
|
Sex: Female, Male
Female
|
83 Participants
n=93 Participants
|
85 Participants
n=4 Participants
|
98 Participants
n=27 Participants
|
266 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
60 Participants
n=93 Participants
|
63 Participants
n=4 Participants
|
48 Participants
n=27 Participants
|
171 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Day 28Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification. Per protocol population (PP). 95% Clopper-Pearson 2-sided Confidence Interval (CI) constructed around the single binomial proportion per treatment arm and total.
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=106 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=117 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=117 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PCR-adjusted ACPR at Day 28 in the PP Population (All Patients)
|
70.8 % ACPR PCR-adjusted
Interval 61.13 to 79.19
|
68.4 % ACPR PCR-adjusted
Interval 59.13 to 76.66
|
78.6 % ACPR PCR-adjusted
Interval 70.09 to 85.67
|
PRIMARY outcome
Timeframe: Day 28Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification. 95% Clopper-Pearson 2-sided CI constructed around the single binomial proportion per treatment arm and total.
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=25 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=25 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=27 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PCR-adjusted ACPR at Day 28 in the PP Population: Asia (All Ages)
|
64 % ACPR PCR-adjusted
Interval 42.52 to 82.03
|
64 % ACPR PCR-adjusted
Interval 42.52 to 82.03
|
70.4 % ACPR PCR-adjusted
Interval 49.82 to 86.25
|
PRIMARY outcome
Timeframe: Day 28Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification. 95% Clopper-Pearson 2-sided CI constructed around the single binomial proportion per treatment arm and total.
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=81 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=92 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=90 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PCR-adjusted ACPR at Day 28 in the PP Population: Africa (All Ages)
|
72.8 % ACPR PCR-adjusted
Interval 61.81 to 82.13
|
69.6 % ACPR PCR-adjusted
Interval 59.1 to 78.73
|
81.1 % ACPR PCR-adjusted
Interval 71.49 to 88.59
|
PRIMARY outcome
Timeframe: Day 28Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification. 95% Clopper-Pearson 2-sided CI constructed around the single binomial proportion per treatment arm and total.
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=18 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=21 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=19 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PCR-adjusted ACPR at Day 28 in the PP Population: Africa (> Than 5 Years)
|
77.8 % ACPR PCR-adjusted
Interval 52.36 to 93.59
|
90.5 % ACPR PCR-adjusted
Interval 69.62 to 98.83
|
89.5 % ACPR PCR-adjusted
Interval 66.86 to 98.7
|
PRIMARY outcome
Timeframe: Day 28Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification. 95% Clopper-Pearson 2-sided CI constructed around the single binomial proportion per treatment arm and total.
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=63 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=71 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=71 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PCR-adjusted ACPR at Day 28 in the PP Population: Africa (< = 5 Years)
|
71.4 % ACPR PCR-adjusted
Interval 58.65 to 82.11
|
63.4 % ACPR PCR-adjusted
Interval 51.1 to 74.5
|
78.9 % ACPR PCR-adjusted
Interval 67.56 to 87.67
|
PRIMARY outcome
Timeframe: Day 28Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification. 95% Clopper-Pearson 2-sided CI constructed around the single binomial proportion per treatment arm and total.
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=45 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=50 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=55 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PCR-adjusted ACPR at Day 28 in the PP Population: Africa (>2 to <= 5 Years)
|
75.6 % ACPR PCR-adjusted
Interval 60.46 to 87.12
|
74.0 % ACPR PCR-adjusted
Interval 59.66 to 85.37
|
83.6 % ACPR PCR-adjusted
Interval 71.2 to 92.23
|
PRIMARY outcome
Timeframe: Day 28Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
PCR-adjusted adequate clinical and parasitological response (ACPR) at Day 28: defined as: absence of parasitaemia on Day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure (ETF), late clinical failure (LCF) or late parasitological failure (LPF). Definition of ETF, LCF and LPF according to a modified standard WHO classification. 95% Clopper-Pearson 2-sided CI constructed around the single binomial proportion per treatment arm and total.
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=18 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=21 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=16 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PCR-adjusted ACPR at Day 28 in the PP Population: Africa (>= 0.5 to <= 2 Years)
|
61.1 % ACPR PCR-adjusted
Interval 35.75 to 82.7
|
38.1 % ACPR PCR-adjusted
Interval 18.11 to 61.56
|
62.5 % ACPR PCR-adjusted
Interval 35.43 to 84.8
|
SECONDARY outcome
Timeframe: Days 42Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
PCR - adjusted adequate clinical and parasitological response at Day 42
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=100 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=108 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=100 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PCR - Adjusted ACPR at Day 42 in the PP Population
|
65.0 % ACPR PCR-adjusted
Interval 54.82 to 74.27
|
65.7 % ACPR PCR-adjusted
Interval 55.99 to 74.6
|
72.0 % ACPR PCR-adjusted
Interval 62.13 to 80.52
|
SECONDARY outcome
Timeframe: Day 63Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
PCR-adjusted adequate clinical and parasitological response at Day 63
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=83 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=90 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=84 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PCR-adjusted ACPR at Day 63 in the PP Population
|
57.8 % ACPR PCR-adjusted
Interval 46.49 to 68.6
|
58.9 % ACPR PCR-adjusted
Interval 48.02 to 69.16
|
69.0 % ACPR PCR-adjusted
Interval 58.02 to 78.69
|
SECONDARY outcome
Timeframe: Day 28Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration. The PP population comprised 93.3% of the randomized population.
Crude adequate clinical and parasitological response at Day 28
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=129 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=136 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=133 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Crude ACPR at Day 28 in the PP Population
|
57.4 % ACPR unadjusted (crude)
Interval 48.36 to 66.03
|
56.6 % ACPR unadjusted (crude)
Interval 47.85 to 65.09
|
66.9 % ACPR unadjusted (crude)
Interval 58.23 to 74.83
|
SECONDARY outcome
Timeframe: Day 42Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Crude adequate clinical and parasitological response at Day 42
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=127 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=134 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=130 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Crude ACPR at Day 42 in the PP Population
|
48.0 % ACPR unajusted (crude)
Interval 39.09 to 57.07
|
48.5 % ACPR unajusted (crude)
Interval 39.79 to 57.29
|
51.5 % ACPR unajusted (crude)
Interval 42.62 to 60.39
|
SECONDARY outcome
Timeframe: Day 63Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration. The PP population comprised 93.3% of the randomized population.
Crude adequate clinical and parasitological response at Day 63
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=114 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=122 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=116 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Crude ACPR at Day 63 in the PP Population
|
42.1 % ACPR unadjusted (crude)
Interval 32.92 to 51.71
|
39.3 % ACPR unadjusted (crude)
Interval 30.62 to 48.59
|
49.1 % ACPR unadjusted (crude)
Interval 39.74 to 58.58
|
SECONDARY outcome
Timeframe: Day 28Population: Intent to Treat (ITT) population : all patients who provided written informed consent, were randomised, received the single dose combination of OZ439/PQP study drug (or part thereof), and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
PCR-adjusted adequate clinical and parasitological response at Day 28. Intent to Treat ( ITT) population.
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=143 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=148 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=146 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PCR-adjusted ACPR at Day 28 in the ITT Population
|
53.8 % ACPR PCR-adjusted
Interval 45.32 to 62.21
|
55.4 % ACPR PCR-adjusted
Interval 47.02 to 63.57
|
65.1 % ACPR PCR-adjusted
Interval 56.75 to 72.76
|
SECONDARY outcome
Timeframe: Day 42Population: Intent to Treat (ITT) population : all patients who provided written informed consent, were randomised, received the single dose combination of OZ439/PQP study drug (or part thereof), and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
PCR-adjusted adequate clinical and parasitological response at Day 42 in the ITT population
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=143 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=148 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=146 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PCR-adjusted ACPR at Day 42 in the ITT Population
|
46.9 % ACPR PCR-adjusted
Interval 38.47 to 55.37
|
48.6 % ACPR PCR-adjusted
Interval 40.36 to 56.99
|
50.0 % ACPR PCR-adjusted
Interval 41.62 to 58.38
|
SECONDARY outcome
Timeframe: Day 63Population: Intent to Treat (ITT) population : all patients who provided written informed consent, were randomised, received the single dose combination of OZ439/PQP study drug (or part thereof), and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
PCR-adjusted adequate clinical and parasitological response at Day 63 in the ITT population
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=136 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=140 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=135 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PCR-adjusted ACPR at Day 63 in the ITT Population
|
36.8 % ACPR PCR-adjusted
Interval 28.67 to 45.45
|
38.6 % ACPR PCR-adjusted
Interval 30.47 to 47.16
|
43.7 % ACPR PCR-adjusted
Interval 35.19 to 52.5
|
SECONDARY outcome
Timeframe: Day 28Population: Intent to Treat (ITT) population : all patients who provided written informed consent, were randomised, received the single dose combination of OZ439/PQP study drug (or part thereof), and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Crude adequate clinical and parasitological response at Day 28 in the ITT population
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=143 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=148 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=146 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Crude ACPR at Day 28 in the ITT Population
|
53.1 % ACPR unadjusted (crude)
Interval 44.63 to 61.53
|
53.4 % ACPR unadjusted (crude)
Interval 45.01 to 61.61
|
63.0 % ACPR unadjusted (crude)
Interval 54.64 to 70.85
|
SECONDARY outcome
Timeframe: Day 42Population: Intent to Treat (ITT) population : all patients who provided written informed consent, were randomised, received the single dose combination of OZ439/PQP study drug (or part thereof), and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Crude adequate clinical and parasitological response at Day 42 in the ITT population
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=143 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=148 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=146 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Crude ACPR at Day 42 in the ITT Population
|
44.1 % ACPR unadjusted (crude)
Interval 35.77 to 52.59
|
44.6 % ACPR unadjusted (crude)
Interval 36.43 to 52.98
|
46.6 % ACPR unadjusted (crude)
Interval 38.29 to 55.01
|
SECONDARY outcome
Timeframe: Day 63Population: Intent to Treat (ITT) population : all patients who provided written informed consent, were randomised, received the single dose combination of OZ439/PQP study drug (or part thereof), and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Crude adequate clinical and parasitological response at Day 63 in the ITT population
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=136 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=140 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=135 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Crude ACPR at Day 63 in the ITT Population
|
36.8 % ACPR unadjusted (crude)
Interval 28.67 to 45.45
|
35.0 % ACPR unadjusted (crude)
Interval 27.14 to 43.51
|
43.0 % ACPR unadjusted (crude)
Interval 34.48 to 51.76
|
SECONDARY outcome
Timeframe: Day 63Population: modified Intent to Treat (mITT) population : all patients who provided written informed consent, were randomised, were compliant with the single dose combination of OZ439/PQP study drug and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Kaplan-Meier estimate of number of recurrent infections (either recrudescence or new infection)
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=141 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=141 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=140 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Kaplan-Meier Estimate of Recurrence
|
44.7 % population recurring
|
54.6 % population recurring
|
43.6 % population recurring
|
SECONDARY outcome
Timeframe: Day 63Population: modified Intent to Treat (mITT) population : all patients who provided written informed consent, were randomised, were compliant with the single dose combination of OZ439/PQP study drug and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Kaplan-Meier estimate of number of patients with recrudescence
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=141 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=141 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=140 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Kaplan-Meier Estimate of Recrudescence
|
22.7 % patients with recrudescence
|
29.1 % patients with recrudescence
|
18.6 % patients with recrudescence
|
SECONDARY outcome
Timeframe: Day 63Population: modified Intent to Treat (mITT) population : all patients who provided written informed consent, were randomised, were compliant with the single dose combination of OZ439/PQP study drug and had a confirmed positive blood film for P. falciparum asexual parasitaemia at inclusion.
Kaplan-Meier estimate of number of patients with new infections
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=141 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=141 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=140 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Kaplan-Meier Estimate of New Infection Rate
|
11.3 % population with new infection
|
16.3 % population with new infection
|
13.6 % population with new infection
|
SECONDARY outcome
Timeframe: 0, 6, 12, 18, 24, 30, 36, 48 and 72 hours post dosePopulation: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Time post dose to parasite clearance
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=139 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=140 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=139 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Parasite Clearance Time
|
36.1 hours
Interval 36.0 to 36.1
|
36.0 hours
Interval 36.0 to 36.1
|
36.1 hours
Interval 36.0 to 36.1
|
SECONDARY outcome
Timeframe: Day 42Population: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration.
Time to fever clearance (hours)
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=139 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=140 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=139 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Fever Clearance Time
|
1.0 hours
Interval 1.0 to 2.6
|
1.2 hours
Interval 1.0 to 2.1
|
1.1 hours
Interval 1.0 to 2.0
|
SECONDARY outcome
Timeframe: 0, 6, 12, 18, 24, 30, 36 and 48 hours post dosePopulation: Primary analysis population was the per protocol population defined as all patients comprising the ITT set and without major protocol deviations. Including insufficient evidence of study indication, no baseline parasitemia and non-compliance with study drug administration. Subjects with sufficient data points to determine PRR48
Parasite reduction ratio at 48 hours post dose
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=97 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=103 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=99 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
PRR48
|
9.120 ratio
Interval 6.9 to 12.97
|
9.300 ratio
Interval 7.66 to 13.34
|
8.690 ratio
Interval 6.85 to 12.26
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 7Piperaquine concentration at Day7 in Asian patients all ages
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=27 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=28 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=28 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Piperaquine: Cday7 Asia (All Ages)
|
4.2 ng/mL
Geometric Coefficient of Variation 72
|
6.9 ng/mL
Geometric Coefficient of Variation 61
|
9.3 ng/mL
Geometric Coefficient of Variation 78
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 7Piperaquine concentration at Day7 in African patients \> 5 years
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=21 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=22 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=21 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Piperaquine: Cday7 Africa (> 5 Years)
|
5.6 ng/mL
Geometric Coefficient of Variation 113
|
8.8 ng/mL
Geometric Coefficient of Variation 105
|
12.1 ng/mL
Geometric Coefficient of Variation 103
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 7Piperaquine concentration at Day7 in African patients \> 2 and \<= 5years
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=43 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=42 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=33 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Piperaquine: Cday7 Africa (>2 to <= 5 Years)
|
6.3 ng/mL
Geometric Coefficient of Variation 71
|
9.2 ng/mL
Geometric Coefficient of Variation 87
|
10.9 ng/mL
Geometric Coefficient of Variation 92
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 7Piperaquine concentration at Day7 in African patients \>= 0.5 and \<= 2 years
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=51 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
n=52 Participants
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
n=59 Participants
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Piperaquine: Cday7 Africa (>=0.5 to <= 2 Years)
|
5.0 ng/mL
Geometric Coefficient of Variation 63
|
5.9 ng/mL
Geometric Coefficient of Variation 70
|
9.0 ng/mL
Geometric Coefficient of Variation 94
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 7Artefenomel concentration on Day 7 in Asian Patients (all ages). All Treatment arms.
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=82 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Artefenomel Cday7 Asian Patients (All Ages)
|
5.1 ng/mL
Geometric Coefficient of Variation 95
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 7Artefenomel concentration on Day 7 in African Patients \> 5 years. All Treatment arms.
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=64 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Artefenomel Cday7 African Patients (> 5 Years)
|
3.3 ng/mL
Geometric Coefficient of Variation 141
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 7Artefenomel concentration on Day 7 in African Patients \>2 to \<= 5 years. All Treatment arms.
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=120 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Artefenomel Cday7 African Patients (>2 to <= 5 Years)
|
3.3 ng/mL
Geometric Coefficient of Variation 142
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 7Artefenomel concentration on Day 7 in African Patients \>= 0.5 to \<=2 years. All Treatment arms.
Outcome measures
| Measure |
A) Artefenomel 800mg: Piperaquine 640mg
n=161 Participants
Artefenomel 800mg: piperaquine 640mg: Active, loose combination
|
B) Artefenomel 800mg: Piperaquine 960mg
Artefenomel 800mg: Piperaquine phosphate 960mg loose combination
|
C) Artefenomel 800mg: Piperaquine 1440mg
Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
|
|---|---|---|---|
|
Artefenomel Cday7 African Patients (>=0.5 to <= 2 Years)
|
2.0 ng/mL
Geometric Coefficient of Variation 147
|
—
|
—
|
Adverse Events
B) Artefenomel 800mg: PQP 960mg
C) Artefenomel 800mg: PQP 1440mg
A) Artefenomel 800mg: PQP 640mg
Serious adverse events
| Measure |
B) Artefenomel 800mg: PQP 960mg
n=148 participants at risk
Artefenomel 800mg: Piperaquine 960mg
|
C) Artefenomel 800mg: PQP 1440mg
n=143 participants at risk
Artefenomel 800mg: Piperaquine 1440mg
|
A) Artefenomel 800mg: PQP 640mg
n=146 participants at risk
Artefenomel 800mg: Piperaquine phosphate 640mg
|
|---|---|---|---|
|
Investigations
Transaminase elevation
|
0.00%
0/148 • From screening up to Day 63 post dose
|
0.70%
1/143 • Number of events 2 • From screening up to Day 63 post dose
|
0.00%
0/146 • From screening up to Day 63 post dose
|
|
Investigations
Anemia
|
0.00%
0/148 • From screening up to Day 63 post dose
|
0.70%
1/143 • Number of events 1 • From screening up to Day 63 post dose
|
0.00%
0/146 • From screening up to Day 63 post dose
|
|
Nervous system disorders
Febrile convulsion
|
0.68%
1/148 • Number of events 1 • From screening up to Day 63 post dose
|
0.00%
0/143 • From screening up to Day 63 post dose
|
0.00%
0/146 • From screening up to Day 63 post dose
|
|
Investigations
Hemoglobin drop < 5 g/dL
|
0.00%
0/148 • From screening up to Day 63 post dose
|
0.00%
0/143 • From screening up to Day 63 post dose
|
0.68%
1/146 • Number of events 1 • From screening up to Day 63 post dose
|
Other adverse events
| Measure |
B) Artefenomel 800mg: PQP 960mg
n=148 participants at risk
Artefenomel 800mg: Piperaquine 960mg
|
C) Artefenomel 800mg: PQP 1440mg
n=143 participants at risk
Artefenomel 800mg: Piperaquine 1440mg
|
A) Artefenomel 800mg: PQP 640mg
n=146 participants at risk
Artefenomel 800mg: Piperaquine phosphate 640mg
|
|---|---|---|---|
|
Infections and infestations
malaria
|
30.4%
45/148 • Number of events 48 • From screening up to Day 63 post dose
|
30.1%
43/143 • Number of events 44 • From screening up to Day 63 post dose
|
23.3%
34/146 • Number of events 34 • From screening up to Day 63 post dose
|
|
Infections and infestations
Bronchitis
|
8.8%
13/148 • Number of events 19 • From screening up to Day 63 post dose
|
9.1%
13/143 • Number of events 16 • From screening up to Day 63 post dose
|
6.8%
10/146 • Number of events 11 • From screening up to Day 63 post dose
|
|
Infections and infestations
Rhinitis
|
6.1%
9/148 • Number of events 10 • From screening up to Day 63 post dose
|
7.7%
11/143 • Number of events 11 • From screening up to Day 63 post dose
|
6.8%
10/146 • Number of events 10 • From screening up to Day 63 post dose
|
|
Infections and infestations
Plasmodium Falciparum Infection
|
6.8%
10/148 • Number of events 10 • From screening up to Day 63 post dose
|
6.3%
9/143 • Number of events 9 • From screening up to Day 63 post dose
|
4.8%
7/146 • Number of events 7 • From screening up to Day 63 post dose
|
|
Investigations
Electrocardiumgram QT prolonged
|
27.7%
41/148 • Number of events 48 • From screening up to Day 63 post dose
|
18.9%
27/143 • Number of events 29 • From screening up to Day 63 post dose
|
30.1%
44/146 • Number of events 56 • From screening up to Day 63 post dose
|
|
Investigations
Neutrophil count decreased
|
7.4%
11/148 • Number of events 11 • From screening up to Day 63 post dose
|
12.6%
18/143 • Number of events 18 • From screening up to Day 63 post dose
|
8.2%
12/146 • Number of events 13 • From screening up to Day 63 post dose
|
|
Investigations
Haemoglobin decreased
|
13.5%
20/148 • Number of events 22 • From screening up to Day 63 post dose
|
6.3%
9/143 • Number of events 9 • From screening up to Day 63 post dose
|
7.5%
11/146 • Number of events 11 • From screening up to Day 63 post dose
|
|
Gastrointestinal disorders
Diarrhoea
|
14.2%
21/148 • Number of events 21 • From screening up to Day 63 post dose
|
7.7%
11/143 • Number of events 12 • From screening up to Day 63 post dose
|
13.7%
20/146 • Number of events 20 • From screening up to Day 63 post dose
|
|
Gastrointestinal disorders
Vomiting
|
13.5%
20/148 • Number of events 20 • From screening up to Day 63 post dose
|
9.8%
14/143 • Number of events 14 • From screening up to Day 63 post dose
|
11.0%
16/146 • Number of events 16 • From screening up to Day 63 post dose
|
|
Gastrointestinal disorders
Abdominal pain
|
5.4%
8/148 • Number of events 9 • From screening up to Day 63 post dose
|
3.5%
5/143 • Number of events 5 • From screening up to Day 63 post dose
|
8.2%
12/146 • Number of events 13 • From screening up to Day 63 post dose
|
|
General disorders
Pyrexia
|
8.1%
12/148 • Number of events 13 • From screening up to Day 63 post dose
|
3.5%
5/143 • Number of events 5 • From screening up to Day 63 post dose
|
6.2%
9/146 • Number of events 11 • From screening up to Day 63 post dose
|
Additional Information
Associate Professor Dr Michael Ramharter
Medical University of Vienna, Division of Infectious Diseases and Tropical Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place