Pyronaridine Artesunate (3:1) Versus Coartem® in P Falciparum Malaria Patients
Study Details
Study Description
Brief Summary
The primary objective of this phase III study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) with that of Coartem® (artemether lumefantrine, AL) in children and adults with uncomplicated P falciparum malaria in Africa and South East Asia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a multi-centre, comparative, randomised, (double-blind, double-dummy), parallel-group, non-inferiority study comparing the efficacy and safety of the fixed combination of PA with that of AL in the treatment of acute, uncomplicated P. falciparum malaria. The study population will include 1269 patients, comprising male and female children (≥20 kg body weight) and adults recruited from study sites in Africa and South East Asia.
Patients will be randomised to receive either oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Days 0, 1, and 2) or AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Days 0, 1, and 2) in a 2:1 ratio. The dose range of PA covered by this regimen is 7.2:2.4 mg/kg to 13.8:4.6 mg/kg, respectively, which has been shown to be effective and safe in Phase I and II studies. Posology will be based on body weight ranges for both the PA and AL regimens.
Patients will be confined 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PA group Pyronaridine artesunate (PA) |
Drug: 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)
Other Names:
|
| Active Comparator: AL group Arthemether lumefantrine (AL) |
Drug: Coartem® (artemether lumefantrine)
AL (20:120mg tablets) twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- PCR-Corrected Adequate Clinical and Parasitological Response (ACPR) Rate 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
- PCR-corrected Adequate Clinical and Parasitological Response (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.
- Crude ACPR (Non-PCR Corrected ACPR) on Day 14 and Day 28 [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.
- Parasite Clearance Time [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.
- Fever Clearance Time [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
- Percentage of Patients With Fever Clearance at Day 1, 2 and 3 [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.
- Proportion of Patients With Parasite Clearance at Day 1, 2 and 3 [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.
- 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]
Incidence of adverse events and of clinically significant laboratory results, ECG, vital signs or physical examination abnormalities.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female patients between the age 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:
-
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,
-
Positive microscopy of P. falciparum with parasite density between 1,000 and 100,000 asexual parasite count/μl of blood.
-
Written informed consent, in accordance with local practice, 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, lumefantrine or artesunate or other artemisinins.
-
Patients with known disturbances of electrolytes balance, e.g., hypokalaemia or hypomagnesaemia.
-
Use of any other antimalarial agent within 2 weeks prior to start of the study as evidenced by a 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.
-
Patients taking any drug which is metabolised by the cytochrome enzyme CYP2D6 (flecainide, metoprol, imipramine, amitriptyline, clomipramine).
-
Received an investigational drug within the past 4 weeks.
-
Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen. (HBsAg) or Hepatitis C antibody (HCV Ab).
-
Known seropositive HIV antibody.
-
Liver function tests [ASAT/ALAT levels] >2.5 times the upper limit of normal range.
-
Known significant renal impairment as indicated by serum creatinine >1.4 mg/dL.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ecole de Santé Publique, Faculté de Médecine, Université de Kinshasa | Kinshasa | Congo, The Democratic Republic of the | ||
| 2 | Farafenni Field Station, c/o: MRC Laboratories | Fajara | Gambia | ||
| 3 | Komfo Anoykye Teaching Hospital | Kumasi | Ghana | ||
| 4 | RSUD TC Hillers | Maumere | Nusa Tenggara Timur | Indonesia | 86113 |
| 5 | Jayapura General Hospital (RSUD) DOK II | Jayapura | Papua | Indonesia | |
| 6 | Siaya District Hospital, Medical Superintendent's office | Siaya | Kenya | ||
| 7 | Malaria Research and Training Center, Faculté de Médecine, de Pharmacie et d'Ondonto-stomatologie | Bamako | Mali | ||
| 8 | Instituto Nacional de Saude, Ministero de Saude | Maputo | Mozambique | ||
| 9 | Puerto Princesa General Hospital | Puerto Princesa | Philippines | ||
| 10 | Service de Parasitologie, Faculté de Médecine, Université Cheikh Anta Diop | Dakar | Dakar Fann | Senegal |
Sponsors and Collaborators
- Medicines for Malaria Venture
- Shin Poong Pharmaceuticals
Investigators
- Study Director: Claude Oeuvray, PhD, Medicines for Malaria Venture
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- SP-C-005-06
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | PA Group | AL Group |
|---|---|---|
| Arm/Group Description | 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) | 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) |
| Period Title: Overall Study | ||
| STARTED | 849 | 423 |
| COMPLETED | 751 | 347 |
| NOT COMPLETED | 98 | 76 |
Baseline Characteristics
| Arm/Group Title | PA Group | AL Group | Total |
|---|---|---|---|
| Arm/Group Description | 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) | 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 of all reporting groups |
| Overall Participants | 849 | 423 | 1272 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
17.2
(11.12)
|
18.0
(11.41)
|
17.5
(11.22)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
359
42.3%
|
192
45.4%
|
551
43.3%
|
| Male |
490
57.7%
|
231
54.6%
|
721
56.7%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Black |
722
85%
|
358
84.6%
|
1080
84.9%
|
| Asian/Oriental |
127
15%
|
65
15.4%
|
192
15.1%
|
| Region of Enrollment (participants) [Number] | |||
| Mozambique |
89
10.5%
|
44
10.4%
|
133
10.5%
|
| Gambia |
72
8.5%
|
34
8%
|
106
8.3%
|
| Mali |
132
15.5%
|
66
15.6%
|
198
15.6%
|
| Senegal |
138
16.3%
|
68
16.1%
|
206
16.2%
|
| Philippines |
67
7.9%
|
36
8.5%
|
103
8.1%
|
| Congo, The Democratic Republic of the |
199
23.4%
|
99
23.4%
|
298
23.4%
|
| Ghana |
4
0.5%
|
3
0.7%
|
7
0.6%
|
| Kenya |
88
10.4%
|
44
10.4%
|
132
10.4%
|
| Indonesia |
60
7.1%
|
29
6.9%
|
89
7%
|
Outcome Measures
| Title | PCR-Corrected Adequate Clinical and Parasitological Response (ACPR) Rate 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 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. |
| Arm/Group Title | PA Group | AL Group |
|---|---|---|
| Arm/Group Description | 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) | 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) |
| Measure Participants | 784 | 386 |
| Number (95% Confidence Interval) [percentage of subjects] |
99.5
|
99.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PA Group, AL Group |
|---|---|---|
| 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 (AL) 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 (AL) 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) and a 5% non-inferiority margin. Non-inferiority was demonstrated if the lower limit of the CI for the difference >-5%. | |
| Statistical Test of Hypothesis | p-Value | 0.578 |
| Comments | If non-inferiority of PA is demonstrated, the p-value associated with a superiority test was calculated based on a 2-sided Chi-square test. If the calculated p-value is <5%, then the superiority of PA compared to AL is statistically demonstrated. | |
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | ACPR percent difference |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 1.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | PCR-corrected Adequate Clinical and Parasitological Response (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 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. |
| Arm/Group Title | PA Group | AL Group |
|---|---|---|
| Arm/Group Description | 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) | 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) |
| Measure Participants | 784 | 386 |
| Number (95% Confidence Interval) [percentage of subjects] |
99.9
|
100
|
| Title | Crude ACPR (Non-PCR Corrected ACPR) on Day 14 and Day 28 |
|---|---|
| Description | 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. |
| Time Frame | Day 14 and 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | PA Group | AL Group |
|---|---|---|
| Arm/Group Description | 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) | 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) |
| Measure Participants | 784 | 386 |
| Cure rate (%) at Day 14 |
100
|
100
|
| Cure rate (%) at Day 28 |
98.9
|
97.2
|
| Title | Parasite Clearance Time |
|---|---|
| Description | 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. |
| Time Frame | Days 0, 3, 7, 14, 21, 28, 35, and 42 (or on any other day if the subject spontaneously returned) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | PA Group | AL Group |
|---|---|---|
| Arm/Group Description | 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) | 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) |
| Measure Participants | 784 | 386 |
| Median (95% Confidence Interval) [hours] |
23.9
|
24.0
|
| Title | Fever Clearance Time |
|---|---|
| Description | 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 |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | PA Group | AL Group |
|---|---|---|
| Arm/Group Description | 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) | 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) |
| Measure Participants | 584 | 299 |
| Median (95% Confidence Interval) [hours] |
7.9
|
8.0
|
| Title | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 2, 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | PA Group | AL Group |
|---|---|---|
| Arm/Group Description | 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) | 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) |
| Measure Participants | 584 | 299 |
| Clearance rate (%) at Day 1 (24h after first dose) |
88.7
|
87.0
|
| Clearance rate (%) at Day 2 (48h after first dose) |
99.0
|
98.7
|
| Clearance rate (%) at Day 3 (72h after first dose) |
99.5
|
99.3
|
| Title | Proportion of Patients With Parasite Clearance at Day 1, 2 and 3 |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 2, 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | PA Group | AL Group |
|---|---|---|
| Arm/Group Description | 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) | 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) |
| Measure Participants | 784 | 386 |
| Clearance rate (%) at Day 1 (24h after first dose) |
68.1
|
52.8
|
| Clearance rate (%) at Day 2 (48h after first dose) |
98.1
|
97.2
|
| Clearance rate (%) at Day 3 (72h after first dose) |
99.5
|
99.7
|
| Title | Adverse Events and Clinically Significant Laboratory Results |
|---|---|
| Description | Incidence 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 consists of all randomized subjects who received any amount of study medication; subjects were analyzed as treated. |
| Arm/Group Title | PA Group | AL Group |
|---|---|---|
| Arm/Group Description | 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) | 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) |
| Measure Participants | 849 | 423 |
| Nr subj. with ≥1 AE |
509
60%
|
241
57%
|
| Nr subj. with ≥1 treatment-related AE |
275
32.4%
|
123
29.1%
|
| Nr subj. with ≥1 SAE |
3
0.4%
|
2
0.5%
|
| Nr pat with ≥1 treatment-related SAE |
0
0%
|
0
0%
|
| Nr subj. with ≥1 severe or life-threatening AE |
10
1.2%
|
5
1.2%
|
| Nr subj. with ≥1 AE leading to death |
0
0%
|
0
0%
|
| Nr subj. ≥1 AE leading to drug discontinuation |
16
1.9%
|
5
1.2%
|
| Nr subj. with ≥1 AE leading to study withdrawal |
19
2.2%
|
6
1.4%
|
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 | PA Group | AL Group | ||
| Arm/Group Description | 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) | 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) | ||
All Cause Mortality |
||||
| PA Group | AL Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/849 (0%) | 0/423 (0%) | ||
Serious Adverse Events |
||||
| PA Group | AL Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/849 (0.4%) | 2/423 (0.5%) | ||
| Immune system disorders | ||||
| Immunosuppression | 0/849 (0%) | 0 | 1/423 (0.2%) | 1 |
| Infections and infestations | ||||
| Parotitis | 1/849 (0.1%) | 1 | 0/423 (0%) | 0 |
| Typhoid fever | 1/849 (0.1%) | 1 | 0/423 (0%) | 0 |
| Urinary tract infection | 1/849 (0.1%) | 1 | 0/423 (0%) | 0 |
| Cerebral malaria | 0/849 (0%) | 0 | 1/423 (0.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| PA Group | AL Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 506/849 (59.6%) | 239/423 (56.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 17/849 (2%) | 17 | 4/423 (0.9%) | 4 |
| Eosinophilia | 60/849 (7.1%) | 60 | 26/423 (6.1%) | 26 |
| Lymphocytosis | 21/849 (2.5%) | 23 | 16/423 (3.8%) | 17 |
| Neutropenia | 41/849 (4.8%) | 45 | 27/423 (6.4%) | 27 |
| Cardiac disorders | ||||
| Bradycardia | 5/849 (0.6%) | 5 | 5/423 (1.2%) | 5 |
| Ear and labyrinth disorders | ||||
| Vertigo | 14/849 (1.6%) | 15 | 6/423 (1.4%) | 6 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 50/849 (5.9%) | 50 | 23/423 (5.4%) | 23 |
| Abdominal pain upper | 13/849 (1.5%) | 13 | 9/423 (2.1%) | 10 |
| Diarrhoea | 17/849 (2%) | 17 | 3/423 (0.7%) | 3 |
| Dyspepsia | 9/849 (1.1%) | 9 | 4/423 (0.9%) | 4 |
| Nausea | 14/849 (1.6%) | 14 | 9/423 (2.1%) | 9 |
| Toothache | 9/849 (1.1%) | 9 | 2/423 (0.5%) | 2 |
| Vomiting | 42/849 (4.9%) | 43 | 15/423 (3.5%) | 15 |
| General disorders | ||||
| Influenza like illness | 30/849 (3.5%) | 30 | 13/423 (3.1%) | 15 |
| Pyrexia | 20/849 (2.4%) | 20 | 10/423 (2.4%) | 10 |
| Infections and infestations | ||||
| Helminthic infection | 13/849 (1.5%) | 13 | 6/423 (1.4%) | 6 |
| Influenza | 7/849 (0.8%) | 7 | 8/423 (1.9%) | 8 |
| Nasopharyngitis | 13/849 (1.5%) | 15 | 5/423 (1.2%) | 5 |
| Oral herpes | 16/849 (1.9%) | 16 | 8/423 (1.9%) | 8 |
| Respiratory tract infection | 10/849 (1.2%) | 12 | 2/423 (0.5%) | 2 |
| Rhinitis | 10/849 (1.2%) | 10 | 9/423 (2.1%) | 9 |
| Upper respiratoty tract infection | 32/849 (3.8%) | 36 | 12/423 (2.8%) | 12 |
| Urinary tract infection | 20/849 (2.4%) | 21 | 9/423 (2.1%) | 9 |
| Investigations | ||||
| Alanine aminotransferase increased | 9/849 (1.1%) | 9 | 0/423 (0%) | 0 |
| Aspartate aminotransferase increased | 21/849 (2.5%) | 23 | 6/423 (1.4%) | 6 |
| Platelet count increased | 16/849 (1.9%) | 19 | 1/423 (0.2%) | 1 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 8/849 (0.9%) | 8 | 8/423 (1.9%) | 8 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 10/849 (1.2%) | 10 | 2/423 (0.5%) | 2 |
| Nervous system disorders | ||||
| Headache | 71/849 (8.4%) | 76 | 41/423 (9.7%) | 42 |
| Renal and urinary disorders | ||||
| Haematuria | 11/849 (1.3%) | 11 | 3/423 (0.7%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 49/849 (5.8%) | 52 | 27/423 (6.4%) | 27 |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Stephan Duparc, MD, Chief Medical Officer |
|---|---|
| Organization | Medicines for Malaria Venture (MMV) |
| Phone | +41 22 555 0300 ext 351 |
| duparcs@mmv.org |
- SP-C-005-06