Pyronaridine - Artesunate (3:1) Versus Mefloquine Plus Artesunate in Plasmodium Falciparum Malaria Patients

• Sponsor: Medicines for Malaria Venture (Other)
• Overall Status: Completed
• CT.gov ID: NCT00403260
• Collaborator: Shin Poong Pharmaceuticals (Industry)
• Enrollment: 1,271
• Locations: 9
• Arms: 2
• Actual Duration (Months): 23
• Patients Per Site: 141.2
• Patients Per Site Per Month: 6.1

Study Details

Study Description

Brief Summary

The primary objective of this phase III clinical study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) with that of the combination of mefloquine plus artesunate (MQ + AS) in children and adults with uncomplicated P falciparum malaria in South East Asia, India and Africa.

Condition or Disease	Intervention/Treatment	Phase
Falciparum Malaria	Drug: Pyronaridine - artesunate; Drug: Mefloquine plus artesunate	Phase 3

Detailed Description

This is a multi-centre, comparative, randomised, open-label, parallel-group, non-inferiority study comparing the efficacy and safety of a fixed combination of PA to a loose combination of MQ + AS for patients with acute, symptomatic, uncomplicated P. falciparum malaria. The study population will include 1271 patients, comprising male and female children (≥20 kg body weight) and adults, recruited from study sites in South East Asia, India and Africa. Patients will be randomised in a 2:1 ratio to receive either oral PA (180:60mg tablets) or MQ (250mg tablets) plus AS (100mg tablets) once a day for 3 consecutive days (Days 0, 1, and 2). The study drug will be administered by a Third-Party Investigator unblinded to the study treatment, while the Investigator remains blinded.

Patients will be confined to the to the study facility for ≥4 days (Days 0, 1, 2, and 3) and remain near the study site for ≥7 days, or once fever and parasite clearance has been confirmed for ≥24 hours - whichever occurs later.

The primary efficacy end point for the study is the proportion of patients with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28. Scheduled follow-up visits will continue until completion of the study at Day 42. In the case of adverse events reported and unresolved at Day 42, patients will be followed up for a further 30 days, or until resolution of the event.

The primary efficacy end point for the study is the proportion of subjects with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28 (defined as the absence of parasitaemia without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure). Scheduled follow-up visits will continue until completion of the study at Day 42. In the case of adverse events reported and unresolved at Day 42, patients will be followed up for a further 30 days, or until resolution of the event.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1271 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Comparative, Open-label, Randomised, Multi-centre Study to Assess the Efficacy of Pyronaridine Artesunate (180:60mg) Versus Mefloquine (250mg) Plus Artesunate (100mg) in Children & Adult Patients With Acute Falciparum Malaria
• Actual Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pyronaridine - artesunate Oral pyronaridine artesunate (180:60mg tablets) once a day for 3 consecutive days (Day 0, 1, and 2). Posology based on body weight ranges.	Drug: Pyronaridine - artesunate; once a day for 3 days; Other Names: Pyramax
Active Comparator: Mefloquine plus artesunate Mefloquine (250mg tablets) plus artesunate (100mg tablets) once a day for 3 consecutive days (Day 0, 1, and 2). Posology based on body weight ranges.	Drug: Mefloquine plus artesunate; once a day for 3 days

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28 [Day 28]

   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.

Secondary Outcome Measures

1. PCR-corrected ACPR on Day 14 [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

2. Crude ACPR on Days 14 and 28 [Days 14 and 28]

   Percentage of subjects with adequate clinical and parasitological response (ACPR) on Days 14 and 28, without correction by PCR, defined as absence of parasitaemia on Days 14 and 28 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure

3. Parasite Clearance Time [Thick blood films were examined every 8 hours until ≥72 hours or until 2 consecutive negative readings occurred 7 to 25 hours apart, and on Days 3, 7, 14, 21, 28, 35, and 42 (or any other day if the subject returned).]

   Parasite clearance time was defined as the time from first dosing to 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.

4. Fever Clearance Time [Every 8 hours over ≥72 hours following first study drug administration or temperature normalisation for ≥2 readings between 7 and 25 hours apart, then at each visit.]

   Fever clearance time was defined as the time from first dosing to first normal reading of temperature (<37.5°C taken axillary or tympanic; <38°C taken oral or rectal) for 2 consecutive normal temperature readings taken between 7 and 25 hours apart.

5. Parasite Clearance at Day 1, 2 and 3 [Days 1, 2 and 3]

   Parasite clearance time was 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.

6. Fever Clearance at Day 1, 2 and 3 [Days 1, 2 and 3]

   Fever clearance time was defined as the time for at least 2 consecutive normal body temperature measurements (<37.5°C axillary/tympanic or <38.0°C oral/rectal) to be obtained within an interval of 7 to 25 hours post-dosing.

7. Adverse Events and Clinically Significant Laboratory Results [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]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female patients between the ages of 3 and 60 years, inclusive.

• Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition.

• Presence of acute uncomplicated P. falciparum mono-infection confirmed by:

1. Fever, as defined by axillary/tympanic temperature ≥37.5°C or oral/rectal temperature ≥38°C, or documented history of fever in the previous 24 hours and,

2. Positive microscopy of P. falciparum with parasite density between 1,000 and 100,000 asexual parasite count/µl of blood

• Written informed consent provided by patient and/or parent/guardian/spouse.

• Ability to swallow oral medication.

Exclusion Criteria:

• Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization Criteria 2000.

• Mixed Plasmodium infection.

• Severe vomiting or severe diarrhoea.

• Known history or evidence of clinically significant disorders.

• Presence of significant anaemia, as defined by Hb <8 g/dL.

• Presence of febrile conditions caused by diseases other than malaria.

• Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, mefloquine or artesunate or other artemisinins.

• Use of any other antimalarial agent within 2 weeks prior to start of the study as evidenced by positive urine test.

• Female patients of child-bearing potential must be neither pregnant (as demonstrated by a negative pregnancy test) nor lactating, and must be willing to take measures to not become pregnant during the study period.

• Presence of significant renal or hepatic impairment.

• Receipt of an investigational drug within the past 4 weeks.

• Known active Hepatitis A IgM, Hepatitis B surface antigen or Hepatitis C antibody.

• Known seropositive HIV antibody.

• Previous participation in any clinical study with PA.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	RAOTAP2/Centre Muraz	Bobo Dioulasso	Houet Province	Burkina Faso	01 BP390
2	Pailin Referral Hospital	Pailin	Pailin Province	Cambodia
3	Institut Pasteur	Abidjan		Côte D'Ivoire
4	Wentlock District Hospital	Mangalore		India
5	Bagamoyo Research and Training Centre of Ifakara Health Institute	Bagamoyo		Tanzania
6	MaeLamad District Hospital	Mae Ramat	Tak Province	Thailand
7	MaeSod General Hospital	Mae Sot	Tak Province	Thailand
8	NIMPE	Hanoi	Commune Xy	Vietnam
9	Choray Hospital, Dak O	Ho Chi Minh City		Vietnam

Sponsors and Collaborators

• Medicines for Malaria Venture
• Shin Poong Pharmaceuticals

Investigators

• Study Director: Isabelle Borghini-Fuhrer, PhD, Medicines for Malaria Venture

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Medicines for Malaria Venture

Publications

None provided.

• Responsible Party: Medicines for Malaria Venture
• ClinicalTrials.gov Identifier: NCT00403260
• Other Study ID Numbers: SP-C-004-06
• First Posted: Nov 23, 2006
• Last Update Posted: Nov 2, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Medicines for Malaria Venture: malaria; antimalarial; P falciparum; pyronaridine; artesunate; artemisinin based combination therapy (ACT); pyronaridine artesunate (Pyramax)
• Additional relevant MeSH terms: Malaria; Malaria, Falciparum; Artesunate; Mefloquine; Pyronaridine

Study Results

Participant Flow

Arm/Group Title	Pyronaridine - Artesunate	Mefloquine Plus Artesunate
Arm/Group Description	Pyronaridine - artesunate (180:60mg) once a day for 3 days. Posology was based on body weight ranges.	Mefloquine (250mg) plus artesunate (100mg) once a day for 3 days. Posology was based on body weight ranges.
Period Title: Overall Study
STARTED	848	423
COMPLETED	723	357
NOT COMPLETED	125	66

Baseline Characteristics

Arm/Group Title	Pyronaridine - Artesunate	Mefloquine Plus Artesunate	Total
Arm/Group Description	Pyronaridine - artesunate (180:60mg) once a day for 3 days. Posology was based on body weight ranges.	Mefloquine (250mg) plus artesunate (100mg) once a day for 3 days. Posology was based on body weight ranges.	Total of all reporting groups
Overall Participants	848	423	1271
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.0 (11.67)	25.4 (12.54)	25.1 (11.96)
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	23	23.0	23.0
Sex: Female, Male (Count of Participants)
Female	214 25.2%	93 22%	307 24.2%
Male	634 74.8%	330 78%	964 75.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	689 81.3%	344 81.3%	1033 81.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	159 18.8%	79 18.7%	238 18.7%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Vietnam	108 12.7%	55 13%	163 12.8%
Burkina Faso	83 9.8%	39 9.2%	122 9.6%
Cambodia	140 16.5%	71 16.8%	211 16.6%
Tanzania	25 2.9%	13 3.1%	38 3%
Côte D'Ivoire	51 6%	27 6.4%	78 6.1%
Thailand	402 47.4%	198 46.8%	600 47.2%
India	39 4.6%	20 4.7%	59 4.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28
Description	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.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Efficacy evaluable population subjects completed a full course of study med., did not miss a dose, did not use a concomitant med. 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, and did not have major protocol deviations.

Arm/Group Title	Pyronaridine - Artesunate	Mefloquine Plus Artesunate
Arm/Group Description	Pyronaridine - artesunate (180:60mg) once a day for 3 days. Posology was based on body weight ranges.	Mefloquine (250mg) plus artesunate (100mg) once a day for 3 days. Posology was based on body weight ranges.
Measure Participants	749	367
Number (95% Confidence Interval) [percentage of subjects]	99.2	98.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pyronaridine - Artesunate, Mefloquine Plus Artesunate
	Comments	Null hypothesis: The PCR-corrected ACPR response rate at Day 28 for the PA group is inferior to the PCR-corrected ACPR response rate at Day 28 for the comparator group (MQ + AS) by more than 5%. Was tested versus the alternative: Alternative hypothesis: the PCR-corrected ACPR response rate at Day 28 for the PA group is not inferior to the PCR-corrected ACPR response rate at Day 28 for the comparator group (MQ + AS) by more than -5%.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The primary efficacy analysis tested the non-inferiority of the PA group compared to the comparator group with regard to the PCR-corrected ACPR response rate at Day 28 using the 2-sided 95% confidence interval (CI) (Newcombe-Wilson score method without continuity correction). Non-inferiority of PA to MQ + AS was concluded if the lower limit of the CI for the difference was >-5%.
Statistical Test of Hypothesis	p-Value	0.106
	Comments	If non-inferiority of PA was demonstrated, the p-value associated with a superiority test is calculated based on a 2-sided Chi-square test. If the calculated p-value is <5%, then the superiority of PA compared to MQ+AS was statistically demonstrated.
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	ACPR percent difference
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -0.2 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	PCR-corrected ACPR on Day 14
Description	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
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

Efficacy evaluable population subjects completed a full course of study med., did not miss a dose, did not use a concomitant med. 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, and did not have major protocol deviations.

Arm/Group Title	Pyronaridine - Artesunate	Mefloquine Plus Artesunate
Arm/Group Description	Pyronaridine - artesunate (180:60mg) once a day for 3 days. Posology was based on body weight ranges.	Mefloquine (250mg) plus artesunate (100mg) once a day for 3 days. Posology was based on body weight ranges.
Measure Participants	749	367
Mean (95% Confidence Interval) [percentage of subjects]	99.9	99.5

3. Secondary Outcome

Title	Crude ACPR on Days 14 and 28
Description	Percentage of subjects with adequate clinical and parasitological response (ACPR) on Days 14 and 28, without correction by PCR, defined as absence of parasitaemia on Days 14 and 28 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure
Time Frame	Days 14 and 28

Outcome Measure Data

Analysis Population Description

Efficacy evaluable population subjects completed a full course of study med., did not miss a dose, did not use a concomitant med. 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, and did not have major protocol deviations.

Arm/Group Title	Pyronaridine - Artesunate	Mefloquine Plus Artesunate
Arm/Group Description	Pyronaridine - artesunate (180:60mg) once a day for 3 days. Posology was based on body weight ranges.	Mefloquine (250mg) plus artesunate (100mg) once a day for 3 days. Posology was based on body weight ranges.
Measure Participants	749	367
Cure rate (%) on Day 14	99.9	99.5
Cure rate (%) on Day 28	98.7	96.7

4. Secondary Outcome

Title	Parasite Clearance Time
Description	Parasite clearance time was defined as the time from first dosing to 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.
Time Frame	Thick blood films were examined every 8 hours until ≥72 hours or until 2 consecutive negative readings occurred 7 to 25 hours apart, and on Days 3, 7, 14, 21, 28, 35, and 42 (or any other day if the subject returned).

Outcome Measure Data

Analysis Population Description

Efficacy evaluable population subjects completed a full course of study med., did not miss a dose, did not use a concomitant med. 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, and did not have major protocol deviations.

Arm/Group Title	Pyronaridine - Artesunate	Mefloquine Plus Artesunate
Arm/Group Description	Pyronaridine - artesunate (180:60mg) once a day for 3 days. Posology was based on body weight ranges.	Mefloquine (250mg) plus artesunate (100mg) once a day for 3 days. Posology was based on body weight ranges.
Measure Participants	749	367
Median (95% Confidence Interval) [hours]	31.7	32.0

5. Secondary Outcome

Title	Fever Clearance Time
Description	Fever clearance time was defined as the time from first dosing to first normal reading of temperature (<37.5°C taken axillary or tympanic; <38°C taken oral or rectal) for 2 consecutive normal temperature readings taken between 7 and 25 hours apart.
Time Frame	Every 8 hours over ≥72 hours following first study drug administration or temperature normalisation for ≥2 readings between 7 and 25 hours apart, then at each visit.

Outcome Measure Data

Analysis Population Description

Efficacy evaluable population subjects completed a full course of study med., did not miss a dose, did not use a concomitant med. 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, and did not have major protocol deviations.

Arm/Group Title	Pyronaridine - Artesunate	Mefloquine Plus Artesunate
Arm/Group Description	Pyronaridine - artesunate (180:60mg) once a day for 3 days. Posology was based on body weight ranges.	Mefloquine (250mg) plus artesunate (100mg) once a day for 3 days. Posology was based on body weight ranges.
Measure Participants	627	313
Median (95% Confidence Interval) [hours]	15.9	16.0

6. Secondary Outcome

Title	Parasite Clearance at Day 1, 2 and 3
Description	Parasite clearance time was 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.
Time Frame	Days 1, 2 and 3

Outcome Measure Data

Analysis Population Description

Efficacy evaluable population subjects completed a full course of study med., did not miss a dose, did not use a concomitant med. 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, and did not have major protocol deviations.

Arm/Group Title	Pyronaridine - Artesunate	Mefloquine Plus Artesunate
Arm/Group Description	Pyronaridine - artesunate (180:60mg) once a day for 3 days. Posology was based on body weight ranges.	Mefloquine (250mg) plus artesunate (100mg) once a day for 3 days. Posology was based on body weight ranges.
Measure Participants	749	367
Clearance rate (%) at Day 1 (24h after first dose)	38.5	31.6
Clearance rate (%) at Day 2 (48h after first dose)	83.8	79.8
Clearance rate (%) at Day 3 (48h after first dose)	91.5	90.5

7. Secondary Outcome

Title	Fever Clearance at Day 1, 2 and 3
Description	Fever clearance time was defined as the time for at least 2 consecutive normal body temperature measurements (<37.5°C axillary/tympanic or <38.0°C oral/rectal) to be obtained within an interval of 7 to 25 hours post-dosing.
Time Frame	Days 1, 2 and 3

Outcome Measure Data

Analysis Population Description

Efficacy evaluable population subjects completed a full course of study med., did not miss a dose, did not use a concomitant med. 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, and did not have major protocol deviations.

Arm/Group Title	Pyronaridine - Artesunate	Mefloquine Plus Artesunate
Arm/Group Description	Pyronaridine - artesunate (180:60mg) once a day for 3 days. Posology was based on body weight ranges.	Mefloquine (250mg) plus artesunate (100mg) once a day for 3 days. Posology was based on body weight ranges.
Measure Participants	627	313
Clearance rate (%) at Day 1 (24h after first dose)	78.5	78.9
Clearance rate (%) at Day 2 (48h after first dose)	95.9	96.2
Clearance rate (%) at Day 3 (72h after first dose)	99.2	98.4

8. Secondary Outcome

Title	Adverse Events and Clinically Significant Laboratory Results
Description	Cases and severity of adverse events and of clinically significant laboratory results, ECG, vital signs or physical examination abnormalities
Time Frame	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

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomised subjects who received any amount of study medication; subjects were analysed as treated.

Arm/Group Title	Pyronaridine - Artesunate	Mefloquine Plus Artesunate
Arm/Group Description	Pyronaridine - artesunate (180:60mg) once a day for 3 days. Posology was based on body weight ranges.	Mefloquine (250mg) plus artesunate (100mg) once a day for 3 days. Posology was based on body weight ranges.
Measure Participants	848	423
Nr subj. with ≥1 AE	389 45.9%	190 44.9%
Nr subj. with ≥1 treatment-related AE	153 18%	94 22.2%
Nr subj. with ≥1 SAE	6 0.7%	3 0.7%
Nr subj. with ≥1 treatment-related SAE	0 0%	2 0.5%
Nr subj. with ≥1 severe or life threatenining AE	24 2.8%	23 5.4%
Nr subj. with ≥1 AE leading to death	0 0%	0 0%
Nr subj with ≥1 AE leading to drug discontinuation	5 0.6%	4 0.9%
Nr subj. with ≥1 AE leading to study withdrawal	5 0.6%	4 0.9%

Adverse Events

Time Frame	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
Adverse Event Reporting Description	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.
Arm/Group Title	Pyronaridine - Artesunate		Mefloquine Plus Artesunate
Arm/Group Description	Pyronaridine artesunate (180:60mg) Pyronaridine artesunate: once a day for 3 days		Mefloquine (250mg) plus artesunate (100mg) Mefloquine plus artesunate: once a day for 3 days
All Cause Mortality
	Pyronaridine - Artesunate		Mefloquine Plus Artesunate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/848 (0%)		0/423 (0%)
Serious Adverse Events
	Pyronaridine - Artesunate		Mefloquine Plus Artesunate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/848 (0.7%)		3/423 (0.7%)
Blood and lymphatic system disorders
Anaemia haemolytic autoimmune	1/848 (0.1%)	1	0/423 (0%)	0
Infections and infestations
Cholera	1/848 (0.1%)	1	0/423 (0%)	0
Pyelonephritis acute	1/848 (0.1%)	1	0/423 (0%)	0
Wound infection	1/848 (0.1%)	1	0/423 (0%)	0
Pneumonia	1/848 (0.1%)	1	0/423 (0%)	0
Cerebral malaria	0/848 (0%)	0	1/423 (0.2%)	1
Nervous system disorders
Grand mal convulsion	0/848 (0%)	0	1/423 (0.2%)	1
Convulsion	0/848 (0%)	0	1/423 (0.2%)	1
Pregnancy, puerperium and perinatal conditions
Abortion complete	1/848 (0.1%)	1	0/423 (0%)	0
Psychiatric disorders
Depression	1/848 (0.1%)	1	0/423 (0%)	0
Other (Not Including Serious) Adverse Events
	Pyronaridine - Artesunate		Mefloquine Plus Artesunate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	389/848 (45.9%)		190/423 (44.9%)
Blood and lymphatic system disorders
Anaemia	31/848 (3.7%)	31	17/423 (4%)	17
Basophilia	8/848 (0.9%)	8	9/423 (2.1%)	9
Eosinophilia	20/848 (2.4%)	20	5/423 (1.2%)	5
Ear and labyrinth disorders
Vertigo	3/848 (0.4%)	3	7/423 (1.7%)	7
Gastrointestinal disorders
Abdominal pain	14/848 (1.7%)	14	7/423 (1.7%)	9
Diarrhoea	10/848 (1.2%)	10	9/423 (2.1%)	9
Nausea	9/848 (1.1%)	9	8/423 (1.9%)	8
Vomiting	18/848 (2.1%)	18	9/423 (2.1%)	9
General disorders
Fatigue	16/848 (1.9%)	18	6/423 (1.4%)	6
Pyrexia	12/848 (1.4%)	12	4/423 (0.9%)	4
Infections and infestations
Bronchitis	15/848 (1.8%)	15	6/423 (1.4%)	6
Nasopharyngitis	21/848 (2.5%)	21	11/423 (2.6%)	11
Investigations
Alanine aminotransferase increased	21/848 (2.5%)	21	0/423 (0%)	0
Aspartate aminotransferase increased	19/848 (2.2%)	19	1/423 (0.2%)	1
Blood creatinine phosphokinase increased	12/848 (1.4%)	12	4/423 (0.9%)	4
Electrocardiogram QT prolonged	1/848 (0.1%)	1	5/423 (1.2%)	5
Eosinophil count increased	9/848 (1.1%)	9	6/423 (1.4%)	6
Haemoglobin decreased	21/848 (2.5%)	21	7/423 (1.7%)	7
Platelet count increased	10/848 (1.2%)	10	3/423 (0.7%)	3
Transaminases increased	18/848 (2.1%)	18	3/423 (0.7%)	3
Metabolism and nutrition disorders
Anorexia	39/848 (4.6%)	41	13/423 (3.1%)	13
Musculoskeletal and connective tissue disorders
Myalgia	53/848 (6.3%)	60	19/423 (4.5%)	20
Nervous system disorders
Dizziness	26/848 (3.1%)	26	28/423 (6.6%)	29
Headache	101/848 (11.9%)	120	44/423 (10.4%)	48
Psychiatric disorders
Insomnia	13/848 (1.5%)	13	8/423 (1.9%)	8
Respiratory, thoracic and mediastinal disorders
Cough	30/848 (3.5%)	33	10/423 (2.4%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.