Trial Outcomes & Findings for Pyronaridine Artesunate (3:1) Versus Coartem® in P Falciparum Malaria Patients (NCT NCT00422084)

NCT ID: NCT00422084

Last Updated: 2021-11-02

Results Overview

Percentage of subjects with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28, defined as absence of parasitaemia on Day 28 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1272 participants

Primary outcome timeframe

Day 28

Results posted on

2021-11-02

Participant Flow

Participant milestones

Participant milestones
Measure	PA Group Pyronaridine artesunate (PA) Pyronaridine artesunate: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)	AL Group Arthemether lumefantrine (AL) Coartem® (artemether lumefantrine): AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
Overall Study STARTED	849	423
Overall Study COMPLETED	751	347
Overall Study NOT COMPLETED	98	76

Reasons for withdrawal

Reasons for withdrawal
Measure	PA Group Pyronaridine artesunate (PA) Pyronaridine artesunate: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)	AL Group Arthemether lumefantrine (AL) Coartem® (artemether lumefantrine): AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
Overall Study Adverse Event	21	7
Overall Study Withdrawal by Subject	12	9
Overall Study Lost to Follow-up	14	9
Overall Study Protocol Violation	4	1
Overall Study Lack of Efficacy	40	42
Overall Study P. vivax infection	3	6
Overall Study Cyesis	1	0
Overall Study Withdrawn from study accidentally	1	0
Overall Study Non-compliance	1	0
Overall Study Re-location	0	1
Overall Study Not defined	1	1

Baseline Characteristics

Pyronaridine Artesunate (3:1) Versus Coartem® in P Falciparum Malaria Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PA Group n=849 Participants Pyronaridine artesunate (PA) Pyronaridine artesunate: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)	AL Group n=423 Participants Arthemether lumefantrine (AL) Coartem® (artemether lumefantrine): AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)	Total n=1272 Participants Total of all reporting groups
Age, Continuous	17.2 years STANDARD_DEVIATION 11.12 • n=5 Participants	18.0 years STANDARD_DEVIATION 11.41 • n=7 Participants	17.5 years STANDARD_DEVIATION 11.22 • n=5 Participants
Sex: Female, Male Female	359 Participants n=5 Participants	192 Participants n=7 Participants	551 Participants n=5 Participants
Sex: Female, Male Male	490 Participants n=5 Participants	231 Participants n=7 Participants	721 Participants n=5 Participants
Race/Ethnicity, Customized Black	722 Participants n=5 Participants	358 Participants n=7 Participants	1080 Participants n=5 Participants
Race/Ethnicity, Customized Asian/Oriental	127 Participants n=5 Participants	65 Participants n=7 Participants	192 Participants n=5 Participants
Region of Enrollment Mozambique	89 participants n=5 Participants	44 participants n=7 Participants	133 participants n=5 Participants
Region of Enrollment Gambia	72 participants n=5 Participants	34 participants n=7 Participants	106 participants n=5 Participants
Region of Enrollment Mali	132 participants n=5 Participants	66 participants n=7 Participants	198 participants n=5 Participants
Region of Enrollment Senegal	138 participants n=5 Participants	68 participants n=7 Participants	206 participants n=5 Participants
Region of Enrollment Philippines	67 participants n=5 Participants	36 participants n=7 Participants	103 participants n=5 Participants
Region of Enrollment Congo, The Democratic Republic of the	199 participants n=5 Participants	99 participants n=7 Participants	298 participants n=5 Participants
Region of Enrollment Ghana	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Kenya	88 participants n=5 Participants	44 participants n=7 Participants	132 participants n=5 Participants
Region of Enrollment Indonesia	60 participants n=5 Participants	29 participants n=7 Participants	89 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 28

Population: Efficacy evaluable population subjects completed a full course of study medication; has a known primary efficacy endpoint at D28; did not miss a dose due to vomiting (except at D0); did not use a concomitant medication (except acetaminophen); did not have a concomitant disease which may have interfered with the classification of the treatment outcome; and did not have major protocol deviations.

Outcome measures

Outcome measures
Measure	PA Group n=784 Participants Pyronaridine artesunate (PA) Pyronaridine artesunate: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)	AL Group n=386 Participants Arthemether lumefantrine (AL) Coartem® (artemether lumefantrine): AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
PCR-Corrected Adequate Clinical and Parasitological Response (ACPR) Rate on Day 28	99.5 percentage of subjects Interval 98.7 to 99.9	99.2 percentage of subjects Interval 97.7 to 99.8

SECONDARY outcome

Timeframe: Day 14

Percentage of subjects with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 14, defined as absence of parasitaemia on Day 14 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure.

Outcome measures

Outcome measures
Measure	PA Group n=784 Participants Pyronaridine artesunate (PA) Pyronaridine artesunate: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)	AL Group n=386 Participants Arthemether lumefantrine (AL) Coartem® (artemether lumefantrine): AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 14	99.9 percentage of subjects Interval 99.3 to 100.0	100 percentage of subjects Interval 99.0 to 100.0

SECONDARY outcome

Timeframe: Day 14 and 28

Percentage of subjects with adequate clinical and parasitological response (ACPR) on Day 28, without correction by PCR, defined as absence of parasitaemia on Day 28 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure.

Outcome measures

Outcome measures
Measure	PA Group n=784 Participants Pyronaridine artesunate (PA) Pyronaridine artesunate: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)	AL Group n=386 Participants Arthemether lumefantrine (AL) Coartem® (artemether lumefantrine): AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
Crude ACPR (Non-PCR Corrected ACPR) on Day 14 and Day 28 Cure rate (%) at Day 14	100 percentage of subjects Interval 99.5 to 100.0	100 percentage of subjects Interval 99.0 to 100.0
Crude ACPR (Non-PCR Corrected ACPR) on Day 14 and Day 28 Cure rate (%) at Day 28	98.9 percentage of subjects Interval 97.8 to 99.5	97.2 percentage of subjects Interval 95.0 to 98.6

SECONDARY outcome

Timeframe: Days 0, 3, 7, 14, 21, 28, 35, and 42 (or on any other day if the subject spontaneously returned)

Parasite clearance time is defined as the time from first dosing to the time of first blood draw with parasite clearance. Parasite clearance is defined as zero presence of asexual parasites for 2 consecutive negative readings taken between 7 and 25 hours apart.

Outcome measures

Outcome measures
Measure	PA Group n=784 Participants Pyronaridine artesunate (PA) Pyronaridine artesunate: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)	AL Group n=386 Participants Arthemether lumefantrine (AL) Coartem® (artemether lumefantrine): AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
Parasite Clearance Time	23.9 hours Interval 23.9 to 23.9	24.0 hours Interval 23.9 to 24.1

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 and as clinically indicated

Fever clearance time is defined as the time from first dosing to first normal reading of temperature for 2 consecutive normal temperature readings taken between 7 and 25 hours apart

Outcome measures

Outcome measures
Measure	PA Group n=584 Participants Pyronaridine artesunate (PA) Pyronaridine artesunate: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)	AL Group n=299 Participants Arthemether lumefantrine (AL) Coartem® (artemether lumefantrine): AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
Fever Clearance Time	7.9 hours Interval 7.9 to 8.0	8.0 hours Interval 7.9 to 15.5

SECONDARY outcome

Timeframe: Days 1, 2, 3

Fever clearance time is defined as the time from first dosing to first normal reading of temperature for 2 consecutive normal temperature readings taken between 7 and 25 hours apart.

Outcome measures

Outcome measures
Measure	PA Group n=584 Participants Pyronaridine artesunate (PA) Pyronaridine artesunate: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)	AL Group n=299 Participants Arthemether lumefantrine (AL) Coartem® (artemether lumefantrine): AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
Percentage of Patients With Fever Clearance at Day 1, 2 and 3 Clearance rate (%) at Day 1 (24h after first dose)	88.7 percentage of subjects Interval 86.0 to 91.1	87.0 percentage of subjects Interval 82.9 to 90.5
Percentage of Patients With Fever Clearance at Day 1, 2 and 3 Clearance rate (%) at Day 2 (48h after first dose)	99.0 percentage of subjects Interval 97.9 to 99.6	98.7 percentage of subjects Interval 96.8 to 99.6
Percentage of Patients With Fever Clearance at Day 1, 2 and 3 Clearance rate (%) at Day 3 (72h after first dose)	99.5 percentage of subjects Interval 98.6 to 99.9	99.3 percentage of subjects Interval 97.8 to 99.9

SECONDARY outcome

Timeframe: Days 1, 2, 3

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

Outcome measures
Measure	PA Group n=784 Participants Pyronaridine artesunate (PA) Pyronaridine artesunate: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)	AL Group n=386 Participants Arthemether lumefantrine (AL) Coartem® (artemether lumefantrine): AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
Proportion of Patients With Parasite Clearance at Day 1, 2 and 3 Clearance rate (%) at Day 1 (24h after first dose)	68.1 percentage of subjects Interval 64.8 to 71.3	52.8 percentage of subjects Interval 48.0 to 57.9
Proportion of Patients With Parasite Clearance at Day 1, 2 and 3 Clearance rate (%) at Day 2 (48h after first dose)	98.1 percentage of subjects Interval 96.9 to 98.9	97.2 percentage of subjects Interval 95.1 to 98.5
Proportion of Patients With Parasite Clearance at Day 1, 2 and 3 Clearance rate (%) at Day 3 (72h after first dose)	99.5 percentage of subjects Interval 98.8 to 99.8	99.7 percentage of subjects Interval 98.6 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 study or resolution of the event, whichever was earlier

Population: The safety population consists of all randomized subjects who received any amount of study medication; subjects were analyzed as treated.

Incidence of adverse events and of clinically significant laboratory results, ECG, vital signs or physical examination abnormalities.

Outcome measures

Outcome measures
Measure	PA Group n=849 Participants Pyronaridine artesunate (PA) Pyronaridine artesunate: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)	AL Group n=423 Participants Arthemether lumefantrine (AL) Coartem® (artemether lumefantrine): AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
Adverse Events and Clinically Significant Laboratory Results Nr subj. with ≥1 AE	509 Participants	241 Participants
Adverse Events and Clinically Significant Laboratory Results Nr subj. with ≥1 treatment-related AE	275 Participants	123 Participants
Adverse Events and Clinically Significant Laboratory Results Nr subj. with ≥1 SAE	3 Participants	2 Participants
Adverse Events and Clinically Significant Laboratory Results Nr pat with ≥1 treatment-related SAE	0 Participants	0 Participants
Adverse Events and Clinically Significant Laboratory Results Nr subj. with ≥1 severe or life-threatening AE	10 Participants	5 Participants
Adverse Events and Clinically Significant Laboratory Results Nr subj. with ≥1 AE leading to death	0 Participants	0 Participants
Adverse Events and Clinically Significant Laboratory Results Nr subj. ≥1 AE leading to drug discontinuation	16 Participants	5 Participants
Adverse Events and Clinically Significant Laboratory Results Nr subj. with ≥1 AE leading to study withdrawal	19 Participants	6 Participants

Adverse Events

PA Group

Serious events: 3 serious events

Other events: 506 other events

Deaths: 0 deaths

AL Group

Serious events: 2 serious events

Other events: 239 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PA Group n=849 participants at risk Pyronaridine artesunate (PA) Pyronaridine artesunate: Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)	AL Group n=423 participants at risk Arthemether lumefantrine (AL) Coartem® (artemether lumefantrine): AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
Infections and infestations Parotitis	0.12% 1/849 • 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 or resolution of the event, whichever was earlier An AE was defined as any unfavorable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study.	0.00% 0/423 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study or resolution of the event, whichever was earlier An AE was defined as any unfavorable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study.
Infections and infestations Typhoid fever	0.12% 1/849 • 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 or resolution of the event, whichever was earlier An AE was defined as any unfavorable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study.	0.00% 0/423 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study or resolution of the event, whichever was earlier An AE was defined as any unfavorable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study.
Infections and infestations Urinary tract infection	0.12% 1/849 • 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 or resolution of the event, whichever was earlier An AE was defined as any unfavorable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study.	0.00% 0/423 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study or resolution of the event, whichever was earlier An AE was defined as any unfavorable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study.
Infections and infestations Cerebral malaria	0.00% 0/849 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study or resolution of the event, whichever was earlier An AE was defined as any unfavorable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study.	0.24% 1/423 • 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 or resolution of the event, whichever was earlier An AE was defined as any unfavorable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study.
Immune system disorders Immunosuppression	0.00% 0/849 • Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study or resolution of the event, whichever was earlier An AE was defined as any unfavorable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study.	0.24% 1/423 • 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 or resolution of the event, whichever was earlier An AE was defined as any unfavorable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study.

Other adverse events

Additional Information

Stephan Duparc, MD, Chief Medical Officer

Medicines for Malaria Venture (MMV)

Phone: +41 22 555 0300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place