Trial Outcomes & Findings for Safety and Efficacy of Pyronaridine Artesunate Vs Chloroquine in Children and Adult Patients With Acute Vivax Malaria (NCT NCT04368910)
NCT ID: NCT04368910
Last Updated: 2022-01-26
Results Overview
Percentage of subjects with crude cure rate at Day 14, defined as absence of parasitaemia on Day 14, irrespective of body temperature without previously meeting any of the criteria of treatment failure
TERMINATED
PHASE3
30 participants
Day 14
2022-01-26
Participant Flow
Participant milestones
| Measure |
Pyronaridine - Artesunate
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
|
Chloroquine
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
|
Overall Study
COMPLETED
|
15
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Efficacy of Pyronaridine Artesunate Vs Chloroquine in Children and Adult Patients With Acute Vivax Malaria
Baseline characteristics by cohort
| Measure |
Pyronaridine - Artesunate
n=15 Participants
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
For patients who complete the study up to Day 28 and who have normal G-6-PD activity, a 14-day course of primaquine (15 mg/day) shall be administered starting on Day 28, after all required assessments have been performed, to complete their radical cure. Patients who are deficient in G-6-PD and who complete the study up to Day 28 will be treated as per country policy.
Pyronaridine - artesunate: Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
|
Chloroquine
n=15 Participants
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
For patients who complete the study up to Day 28 and who have normal G-6-PD activity, a 14-day course of primaquine (15 mg/day) shall be administered starting on Day 28, after all required assessments have been performed, to complete their radical cure. Patients who are deficient in G-6-PD and who complete the study up to Day 28 will be treated as per country policy.
Chloroquine: Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.2 years
STANDARD_DEVIATION 14.03 • n=99 Participants
|
42.3 years
STANDARD_DEVIATION 11.79 • n=107 Participants
|
40.3 years
STANDARD_DEVIATION 12.90 • n=206 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian/Oriental
|
15 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
30 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Day 14Population: Efficacy evaluable population: completed a full course of study medication, did not miss a dose, did not use a concomitant medication that may have interfered with the treatment outcome up to D14, did not have a concomitant disease which may have interfered with the classification of the treatment outcome, did not have major protocol deviations.
Percentage of subjects with crude cure rate at Day 14, defined as absence of parasitaemia on Day 14, irrespective of body temperature without previously meeting any of the criteria of treatment failure
Outcome measures
| Measure |
Pyronaridine - Artesunate
n=13 Participants
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
|
Chloroquine
n=15 Participants
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
|
|---|---|---|
|
Crude Cure Rate on Day 14
|
100 percentage of participants
Interval 75.3 to 100.0
|
100 percentage of participants
Interval 78.2 to 100.0
|
SECONDARY outcome
Timeframe: Day 28Population: Efficacy evaluable population: completed a full course of study medication, did not miss a dose, did not use a concomitant medication that may have interfered with the treatment outcome up to D14, did not have a concomitant disease which may have interfered with the classification of the treatment outcome, did not have major protocol deviations.
Percentage of subjects with crude cure rate at Day 28, defined as absence of parasitaemia on Day 28, irrespective of body temperature without previously meeting any of the criteria of treatment failure
Outcome measures
| Measure |
Pyronaridine - Artesunate
n=13 Participants
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
|
Chloroquine
n=15 Participants
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
|
|---|---|---|
|
Crude Cure Rate on Day 28
|
100 percentage of participants
Interval 75.3 to 100.0
|
100 percentage of participants
Interval 78.2 to 100.0
|
SECONDARY outcome
Timeframe: Days 0, 3, 7, 14, 21, 28, 35, and 42 (or on any other day if the subject spontaneously returned within the 42-day period)Population: Efficacy evaluable population: completed a full course of study medication, did not miss a dose, did not use a concomitant medication that may have interfered with the treatment outcome up to D14, did not have a concomitant disease which may have interfered with the classification of the treatment outcome, did not have major protocol deviations.
Parasite clearance time is defined as the time from first dosing to the time of first blood draw with parasite clearance. Parasite clearance was defined as zero presence of asexual parasites for 2 consecutive negative readings taken between 7 and 25 hours apart
Outcome measures
| Measure |
Pyronaridine - Artesunate
n=13 Participants
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
|
Chloroquine
n=15 Participants
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
|
|---|---|---|
|
Parasite Clearance Time (PCT)
|
32.0 hours
Interval 24.0 to 40.0
|
63.9 hours
Interval 55.9 to 160.8
|
SECONDARY outcome
Timeframe: Day 0 and every 8 hours over ≥72 hours following first study drug administration or temperature normalization for ≥2 readings between 7 and 25 hours apart, then at each visit (Days 7, 14, 28 and 42)Population: Efficacy evaluable population: completed a full course of study medication, did not miss a dose, did not use a concomitant medication that may have interfered with the treatment outcome up to D14, did not have a concomitant disease which may have interfered with the classification of the treatment outcome, did not have major protocol deviations.
Fever clearance time is defined as the time from first dosing to the first normal reading of temperature for 2 consecutive normal temperature readings taken between 7 and 25 hours apart
Outcome measures
| Measure |
Pyronaridine - Artesunate
n=13 Participants
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
|
Chloroquine
n=15 Participants
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
|
|---|---|---|
|
Fever Clearance Time (FCT)
|
16.0 hours
Interval 15.9 to 24.0
|
31.9 hours
Interval 23.5 to 39.8
|
SECONDARY outcome
Timeframe: Days 1, 2, and 3Population: Efficacy evaluable population: completed a full course of study medication, did not miss a dose, did not use a concomitant medication that may have interfered with the treatment outcome up to D14, did not have a concomitant disease which may have interfered with the classification of the treatment outcome, did not have major protocol deviations.
Parasite clearance is defined as at least 2 consecutive negative smears for asexual parasites obtained within an interval of 7 to 25 hours post-dosing
Outcome measures
| Measure |
Pyronaridine - Artesunate
n=13 Participants
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
|
Chloroquine
n=15 Participants
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
|
|---|---|---|
|
Percentage of Patients Who Had Cleared Parasite on Days 1, 2, and 3
Day 1 (24h after first dose)
|
30.8 percentage of participants
Interval 5.7 to 55.9
|
0.0 percentage of participants
Interval 0.0 to 0.0
|
|
Percentage of Patients Who Had Cleared Parasite on Days 1, 2, and 3
Day 2 (48h after first dose)
|
92.3 percentage of participants
Interval 77.8 to 100.0
|
26.7 percentage of participants
Interval 4.3 to 49.0
|
|
Percentage of Patients Who Had Cleared Parasite on Days 1, 2, and 3
Day 3 (72h after first dose)
|
100.0 percentage of participants
Interval 100.0 to 100.0
|
60.0 percentage of participants
Interval 35.2 to 84.8
|
SECONDARY outcome
Timeframe: Days 1, 2, and 3Population: Efficacy evaluable population: completed a full course of study medication, did not miss a dose, did not use a concomitant medication that may have interfered with the treatment outcome up to D14, did not have a concomitant disease which may have interfered with the classification of the treatment outcome, did not have major protocol deviations.
Fever clearance is defined as at least 2 consecutive normal body temperature measurements (\<37.5 C axillary/tympanic or \<38.0 C oral/rectal) obtained within an interval of 7 to 25 hours postdosing
Outcome measures
| Measure |
Pyronaridine - Artesunate
n=13 Participants
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
|
Chloroquine
n=15 Participants
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
|
|---|---|---|
|
Percentage of Patients Who Had Cleared Fever on Days 1, 2, and 3
Clearance rate (%) at Day 1 (24h after first dose)
|
76.9 percentage of participants
Interval 54.0 to 99.8
|
41.7 percentage of participants
Interval 13.8 to 69.6
|
|
Percentage of Patients Who Had Cleared Fever on Days 1, 2, and 3
Clearance rate (%) at Day 2 (48h after first dose)
|
92.3 percentage of participants
Interval 77.8 to 100.0
|
91.7 percentage of participants
Interval 76.0 to 100.0
|
|
Percentage of Patients Who Had Cleared Fever on Days 1, 2, and 3
Clearance rate (%) at Day 3 (72h after first dose)
|
100.0 percentage of participants
Interval 100.0 to 100.0
|
100.0 percentage of participants
Interval 100.0 to 100.0
|
SECONDARY outcome
Timeframe: Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of studyPopulation: Safety population, consisting of all randomised subjects who received any amount of study medication; subjects were analysed as treated.
Number of Participants with AEs, including clinically significant laboratory results, electrocardiogram (ECG), vital signs or physical examination abnormalities
Outcome measures
| Measure |
Pyronaridine - Artesunate
n=15 Participants
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
|
Chloroquine
n=15 Participants
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Nr subj. with ≥1 AE
|
10 Participants
|
10 Participants
|
|
Number of Participants With Adverse Events (AEs)
Nr subj. with ≥1 treatment-related AE
|
7 Participants
|
9 Participants
|
|
Number of Participants With Adverse Events (AEs)
Nr subj. with ≥1 SAE
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Nr subj. with ≥1 treatment-related SAE
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Nr subj. with ≥1 severe or life-threatening AE
|
0 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events (AEs)
Nr subj. with ≥1 AE leading to death
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Nr subj. with≥1 AE leading to drug discontinuation
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Nr subj. with ≥1 AE leading to study withdrawal
|
0 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 42Population: Efficacy evaluable population: completed a full course of study medication, did not miss a dose, did not use a concomitant medication that may have interfered with the treatment outcome up to D14, did not have a concomitant disease which may have interfered with the classification of the treatment outcome, did not have major protocol deviations.
Proportion of subjects with crude cure rate at Day 42, defined as absence of parasitaemia on Day 42, irrespective of body temperature without previously meeting any of the criteria of treatment failure
Outcome measures
| Measure |
Pyronaridine - Artesunate
n=13 Participants
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
|
Chloroquine
n=15 Participants
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
|
|---|---|---|
|
Crude Cure Rate on Day 42
|
100 percentage of subjects
Interval 75.3 to 100.0
|
100 percentage of subjects
Interval 78.2 to 100.0
|
Adverse Events
Pyronaridine - Artesunate
Chloroquine
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Pyronaridine - Artesunate
n=15 participants at risk
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
|
Chloroquine
n=15 participants at risk
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Cardiac disorders
Left ventricular hypertrophy
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Gastrointestinal disorders
Dyspepsia
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
General disorders
Fatigue
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Infections and infestations
Hordeolum
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Infections and infestations
Nasopharyngitis
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Investigations
Alanine aminotransferase increased
|
26.7%
4/15 • Number of events 4 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
13.3%
2/15 • Number of events 2 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Investigations
Aspartate aminotransferase increased
|
26.7%
4/15 • Number of events 4 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Investigations
Haemoglobin decreased
|
13.3%
2/15 • Number of events 2 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
20.0%
3/15 • Number of events 3 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Investigations
Haematocrit decreased
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Investigations
Platelet count decreased
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Investigations
Red blood cell count decreased
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Investigations
White blood cell count increased
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Investigations
Electrocardiogram T wave inversion
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Investigations
Transaminases increased
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Investigations
Weight decreased
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Metabolism and nutrition disorders
Anorexia
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Nervous system disorders
Headache
|
26.7%
4/15 • Number of events 4 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
|
Vascular disorders
Hypotension
|
0.00%
0/15 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
6.7%
1/15 • Number of events 1 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place