Malaria
Conditions
Keywords
P vivax, malaria, artemisinin based combination therapy (ACT), antimalarial, pyronaridine artesunate (Pyramax)
Brief summary
The purpose of this study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) (180:60 mg) with that of standard chloroquine therapy in children and adults with acute, uncomplicated Plasmodium vivax malaria.
Detailed description
This is a multi-centre, randomised, double-blind, double-dummy, parallel-group, non-inferiority study comparing the efficacy and safety of the fixed combination of pyronaridine/artesunate (ie, PP/AS \[PA\]) (180:60 mg) with that of standard chloroquine therapy in children and adults with acute uncomplicated P. vivax malaria. The study population will include 456 patients, comprising male and female children (≥20 kg body weight) and adults recruited from study sites in South East Asia and India. Patients will be randomised in a 1:1 ratio to receive either oral PA (180:60 mg tablets) plus chloroquine-placebo or oral chloroquine (155 mg tablets).plus PA-placebo, once a day for 3 consecutive days (Days 0, 1, and 2). For PA, posology was based on body weight ranges with subjects receiving 1 to 4 tablets depending on their body weight. The dose range covered by this regimen is 7.2:2.4 mg/kg to 13.8:4.6 mg/kg, which has been shown to be effective and safe in Phase I and II studies. The chloroquine daily dose is 10 mg/kg on Days 0 and 1 and 5 mg/kg on Day 2 for children, and 620 mg on Days 0 and 1 and 310 mg on Day 2 for adults. Patients will be confined to the study facility for ≥4 days (Days 0,1,2 & 3) and ideally 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 crude cure rate on Day 14, which is defined as the absence of P. vivax parasitaemia on Day 14. 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. For patients who complete the study up to Day 28 and who have normal glucose-6-phosphate dehydrogenase (G-6-PD) activity, a 14-day course of primaquine (15 mg/day for adults and 0.3 mg/kg/day for children) will be administered starting on Day 28 to complete their radical cure. Subjects who are deficient in G-6-PD and who completed the study up to Day 28 will be treated per country policy.
Interventions
DRUGChloroquine
Sponsors
Shin Poong Pharmaceuticals
Medicines for Malaria Venture
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
3 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients between the age of 3 and 60 years, inclusive. 2. Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition. 3. Presence of acute uncomplicated P. vivax mono-infection confirmed by: * Fever, as defined by axillary/tympanic temperature ≥37.5°C or oral/rectal temperature ≥38°C, or history of fever in the previous 24 hours (history of fever must be documented) and, * Positive microscopy of P. vivax with parasite density ≥250/ mcL of blood (including at least 50% of asexual parasites). 4. Written informed consent, in accordance with local practice, provided by patient and/or parent/guardian/spouse. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations. 5. Ability to swallow oral medication. 6. Ability and willingness to participate based on information given to patient or parent or guardian and access to health facility.
Exclusion criteria
1. Presence of a mixed Plasmodium infection. 2. Presence of other clinical condition requiring hospitalization. 3. Presence of significant anaemia, as defined by Hb \<8 g/dL. 4. Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval ≥450 msec), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric or other abnormality (including recent head trauma). 5. Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, chloroquine or artesunate or other artemisinins. 6. Known history of hypersensitivity, allergic or adverse reactions to chloroquine, primaquine and related agents. 7. Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab). 8. Known seropositive HIV antibody. 9. Have received any antimalarial treatment in the preceding 2 weeks, as determined by history and, whenever feasible, by screening test. 10. Have received antibacterial with known antimalarial activity in the preceding 2 weeks. 11. Have received any investigational drug within the past 4 weeks. 12. Liver function tests (AST/ALT levels) \>2.5 times the upper limit of normal range. 13. Known significant renal impairment as indicated by serum creatinine levels of \>1.4 mg/dL. 14. 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. 15. Previous participation in the present clinical trial with PA.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Crude Cure Rate on Day 14 | Day 14 | Cure rate on Day 14 is defined as the absence of P. vivax parasitaemia on Day 14 irrespective of temperature (axillary, oral, tympanic, rectal) without previously meeting any of the criteria of treatment failure throughout the follow-up period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Crude Cure Rate on Days 21 and 28. | Day 21 and 28 | Cure on Day 21 and 28 is defined as the absence of P. vivax parasitaemia on Day 21 and 28 irrespective of temperature (axillary, oral, tympanic, rectal) without previously meeting any of the criteria of treatment failure throughout the follow-up period. |
| Parasite Clearance Time | Days 0 to 42 | 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 | Days 0 to 42 | Fever clearance time is defined as the time from first dosing to the first normal reading of temperature (\<37.5°C for axillary/tympanic or \<38°C for oral/rectal) for 2 consecutive normal temperature readings taken between 7 and 25 hours apart. |
| Percentage of Subjects With Fever Clearance on Days 1, 2, and 3 | Day 1, 2, and 3 | Percentage of subjects with fever clearance on Day 1 (24 hours after first dose), Day 2 (48 hours after first dose), and Day 3 (72 hours after first dose). |
| Number of Participants With Adverse Events | 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 | Number of participants with adverse events, including clinically significant laboratory results, ECG, vital signs or physical examination abnormalities. |
| Percentage of Subjects With Parasite Clearance on Days 1, 2, and 3 | Days 1, 2, and 3 | Percentage of subjects with parasite clearance on Day 1 (24 hours after first dose), Day 2 (48 hours after first dose), and Day 3 (72 hours after first dose). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With PCR-corrected Cure Rate on Days 14, 21, and 28 | Day 14, 21, and 28 | Cure on Days 14, 21, and 28 is defined as the absence of P. vivax parasitaemia on Days 14, 21, and 28 irrespective of temperature (axillary, oral, tympanic, rectal) without previously meeting any of the criteria of treatment failure throughout the follow-up period. |
| Percentage of Subjects With Crude and PCR-corrected Cure Rate on Day 42 | Day 42 | Cure on Day 42 is defined as the absence of P. vivax parasitaemia on Day 42 irrespective of temperature (axillary, oral, tympanic, rectal) without previously meeting any of the criteria of treatment failure throughout the follow-up period. |
Countries
Cambodia, India, Indonesia, Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pyronaridine - Artesunate Subjects receive oral active-pyronaridine artesunate (tablet 180:60 mg) + chloroquine-placebo, once a day for 3 consecutive days (D0, 1, and 2).
Posology was based on body weight ranges with subjects receiving 1 to 4 tablets depending on their body weight. The actual dose range covered by this regimen was 7.2:2.4 mg/kg to 13.8:4.6 mg/kg. | 228 |
| Chloroquine Subjects receive oral active-chloroquine (tablet 155 mg) + pyronaridine artesunate - placebo, once per day for 3 consecutive days (D0, 1, and 2).
The daily dose is 10 mg/kg on Days 0 and 1, and 5 mg/kg on Day 2 for children, and 620 mg on Days 0 and 1, and 310 mg on Day 2 for adults. | 228 |
| Total | 456 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lack of Efficacy | 6 | 7 |
| Overall Study | Lost to Follow-up | 19 | 12 |
| Overall Study | Mixed infection at entry | 1 | 0 |
| Overall Study | P. falciparum malaria | 5 | 14 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Subjets missed the visit | 1 | 0 |
| Overall Study | Subj left hosp without inform staff | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 5 |
Baseline characteristics
| Characteristic | Pyronaridine - Artesunate | Total | Chloroquine |
|---|---|---|---|
| Age, Continuous Cambodia | 21.0 years STANDARD_DEVIATION 8.93 | 22.0 years STANDARD_DEVIATION 9.46 | 23.0 years STANDARD_DEVIATION 9.92 |
| Age, Continuous India | 31.5 years STANDARD_DEVIATION 12.2 | 29.7 years STANDARD_DEVIATION 12.15 | 27.9 years STANDARD_DEVIATION 11.99 |
| Age, Continuous Indonesia/Maumere | 26.7 years STANDARD_DEVIATION 10.59 | 23.0 years STANDARD_DEVIATION 10.54 | 18.6 years STANDARD_DEVIATION 9.07 |
| Age, Continuous Thailand/Mae Ramat | 30.5 years STANDARD_DEVIATION 9.93 | 29.7 years STANDARD_DEVIATION 10.47 | 29.0 years STANDARD_DEVIATION 11.04 |
| Age, Continuous Thailand/Mae Sot | 29.6 years STANDARD_DEVIATION 11.15 | 29.6 years STANDARD_DEVIATION 10.44 | 29.6 years STANDARD_DEVIATION 9.8 |
| Age, Continuous Total | 27.0 years STANDARD_DEVIATION 11.7 | 26.7 years STANDARD_DEVIATION 11.04 | 26.4 years STANDARD_DEVIATION 10.93 |
| Age, Customized ≤12 years | 14 Participants | 27 Participants | 13 Participants |
| Age, Customized >12 years | 214 Participants | 429 Participants | 215 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 228 Participants | 456 Participants | 228 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Cambodia | 77 participants | 154 participants | 77 participants |
| Region of Enrollment India | 39 participants | 80 participants | 41 participants |
| Region of Enrollment Indonesia | 13 participants | 24 participants | 11 participants |
| Region of Enrollment Thailand | 99 participants | 198 participants | 99 participants |
| Sex: Female, Male Cambodia Female | 25 Participants | 52 Participants | 27 Participants |
| Sex: Female, Male Cambodia Male | 52 Participants | 102 Participants | 50 Participants |
| Sex: Female, Male India Female | 5 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male India Male | 34 Participants | 68 Participants | 34 Participants |
| Sex: Female, Male Indonesia/Maumere Female | 6 Participants | 9 Participants | 3 Participants |
| Sex: Female, Male Indonesia/Maumere Male | 7 Participants | 15 Participants | 8 Participants |
| Sex: Female, Male Thailand/Mae Ramat Female | 9 Participants | 25 Participants | 16 Participants |
| Sex: Female, Male Thailand/Mae Ramat Male | 41 Participants | 74 Participants | 33 Participants |
| Sex: Female, Male Thailand/Mae Sot Female | 11 Participants | 22 Participants | 11 Participants |
| Sex: Female, Male Thailand/Mae Sot Male | 38 Participants | 77 Participants | 39 Participants |
| Sex: Female, Male Total Female | 56 Participants | 120 Participants | 64 Participants |
| Sex: Female, Male Total Male | 172 Participants | 336 Participants | 164 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 228 | 0 / 228 |
| other Total, other adverse events | 90 / 228 | 72 / 228 |
| serious Total, serious adverse events | 2 / 228 | 0 / 228 |
Outcome results
Primary
Crude Cure Rate on Day 14
Cure rate on Day 14 is defined as the absence of P. vivax parasitaemia on Day 14 irrespective of temperature (axillary, oral, tympanic, rectal) without previously meeting any of the criteria of treatment failure throughout the follow-up period.
Time frame: Day 14
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | Gender - Female | 53 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | Cambodia | 75 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | India | 33 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | Previous P. vivax episode in the past = no | 107 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | Previous P. vivax episode in the past = yes | 110 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | Indonesia/Maumere | 11 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | Thailand/Mae Sot | 49 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | Thailand/Mae Ramat | 50 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | baseline P. vivax = 250-5,000/uL | 69 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | baseline P. vivax = >5,000/uL-10,000/uL | 58 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | baseline P. vivax = >10,000/uL | 89 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | age ≤ 12 years | 13 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | age ≥ 12 years | 204 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | Gender - Male | 164 Participants |
| Pyronaridine Artesunate | Crude Cure Rate on Day 14 | Total cured | 217 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | baseline P. vivax = >10,000/uL | 70 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | Total cured | 209 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | Thailand/Mae Ramat | 47 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | Cambodia | 73 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | age ≥ 12 years | 198 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | India | 33 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | Gender - Female | 61 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | baseline P. vivax = 250-5,000/uL | 80 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | Previous P. vivax episode in the past = no | 93 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | age ≤ 12 years | 11 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | Previous P. vivax episode in the past = yes | 116 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | baseline P. vivax = >5,000/uL-10,000/uL | 59 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | Indonesia/Maumere | 10 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | Gender - Male | 148 Participants |
| Chloroquine | Crude Cure Rate on Day 14 | Thailand/Mae Sot | 46 Participants |
Comparison: Null hypothesis: The cure rate on Day 14 for the PA group is inferior to the cure rate on Day 14 for the chloroquine group by more than 10%.~Was tested against the alternative:~Alternative hypothesis: The cure rate on Day 14 for the PA group was not inferior to the cure rate on Day 14 for the chloroquine group by more than 10%.95% CI: [-2.6, 1.4]
Secondary
Crude Cure Rate on Days 21 and 28.
Cure on Day 21 and 28 is defined as the absence of P. vivax parasitaemia on Day 21 and 28 irrespective of temperature (axillary, oral, tympanic, rectal) without previously meeting any of the criteria of treatment failure throughout the follow-up period.
Time frame: Day 21 and 28
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pyronaridine Artesunate | Crude Cure Rate on Days 21 and 28. | Cure rate (%) at Day 21 | 99.5 percentage of cured subjects |
| Pyronaridine Artesunate | Crude Cure Rate on Days 21 and 28. | Cure rate (%) at Day 28 | 97.1 percentage of cured subjects |
| Chloroquine | Crude Cure Rate on Days 21 and 28. | Cure rate (%) at Day 21 | 99.5 percentage of cured subjects |
| Chloroquine | Crude Cure Rate on Days 21 and 28. | Cure rate (%) at Day 28 | 98.0 percentage of cured subjects |
Secondary
Fever Clearance Time
Fever clearance time is defined as the time from first dosing to the first normal reading of temperature (\<37.5°C for axillary/tympanic or \<38°C for oral/rectal) for 2 consecutive normal temperature readings taken between 7 and 25 hours apart.
Time frame: Days 0 to 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pyronaridine Artesunate | Fever Clearance Time | 15.8 hours |
| Chloroquine | Fever Clearance Time | 23.8 hours |
Secondary
Number of Participants With Adverse Events
Number of participants with adverse events, including 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
Population: Safety population consists of all randomized subjects who received any amount of study medication, subjects were analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pyronaridine Artesunate | Number of Participants With Adverse Events | Nr subj. with ≥1 AE | 92 Participants |
| Pyronaridine Artesunate | Number of Participants With Adverse Events | Nr subj. with ≥1 treatment-related AE | 27 Participants |
| Pyronaridine Artesunate | Number of Participants With Adverse Events | Nr subj. with ≥1 SAE | 2 Participants |
| Pyronaridine Artesunate | Number of Participants With Adverse Events | Nr subj. with ≥1 treatment-related SAE | 0 Participants |
| Pyronaridine Artesunate | Number of Participants With Adverse Events | Nr subj. with ≥1 severe or life-threatening AE | 0 Participants |
| Pyronaridine Artesunate | Number of Participants With Adverse Events | Nr subj. with ≥1 AE leading to death | 0 Participants |
| Pyronaridine Artesunate | Number of Participants With Adverse Events | Nr subj. ≥1 AE leading to study drug discontinuation | 0 Participants |
| Pyronaridine Artesunate | Number of Participants With Adverse Events | Nr subj. with ≥1 AE leading to study withdrawal | 0 Participants |
| Chloroquine | Number of Participants With Adverse Events | Nr subj. with ≥1 AE leading to study withdrawal | 2 Participants |
| Chloroquine | Number of Participants With Adverse Events | Nr subj. with ≥1 AE | 72 Participants |
| Chloroquine | Number of Participants With Adverse Events | Nr subj. with ≥1 severe or life-threatening AE | 2 Participants |
| Chloroquine | Number of Participants With Adverse Events | Nr subj. with ≥1 treatment-related AE | 23 Participants |
| Chloroquine | Number of Participants With Adverse Events | Nr subj. ≥1 AE leading to study drug discontinuation | 2 Participants |
| Chloroquine | Number of Participants With Adverse Events | Nr subj. with ≥1 SAE | 0 Participants |
| Chloroquine | Number of Participants With Adverse Events | Nr subj. with ≥1 AE leading to death | 0 Participants |
| Chloroquine | Number of Participants With Adverse Events | Nr subj. with ≥1 treatment-related SAE | 0 Participants |
Secondary
Parasite Clearance Time
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 to 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pyronaridine Artesunate | Parasite Clearance Time | 23.1 hours |
| Chloroquine | Parasite Clearance Time | 32.0 hours |
Secondary
Percentage of Subjects With Fever Clearance on Days 1, 2, and 3
Percentage of subjects with fever clearance on Day 1 (24 hours after first dose), Day 2 (48 hours after first dose), and Day 3 (72 hours after first dose).
Time frame: Day 1, 2, and 3
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pyronaridine Artesunate | Percentage of Subjects With Fever Clearance on Days 1, 2, and 3 | Clearance rate (%) at Day 1 (24h after first dose) | 78.6 percentage of subjects |
| Pyronaridine Artesunate | Percentage of Subjects With Fever Clearance on Days 1, 2, and 3 | Clearance rate (%) at Day 2 (48h after first dose) | 89.9 percentage of subjects |
| Pyronaridine Artesunate | Percentage of Subjects With Fever Clearance on Days 1, 2, and 3 | Clearance rate (%) at Day 3 (72h after first dose) | 97.0 percentage of subjects |
| Chloroquine | Percentage of Subjects With Fever Clearance on Days 1, 2, and 3 | Clearance rate (%) at Day 1 (24h after first dose) | 58.4 percentage of subjects |
| Chloroquine | Percentage of Subjects With Fever Clearance on Days 1, 2, and 3 | Clearance rate (%) at Day 2 (48h after first dose) | 88.3 percentage of subjects |
| Chloroquine | Percentage of Subjects With Fever Clearance on Days 1, 2, and 3 | Clearance rate (%) at Day 3 (72h after first dose) | 97.4 percentage of subjects |
Secondary
Percentage of Subjects With Parasite Clearance on Days 1, 2, and 3
Percentage of subjects with parasite clearance on Day 1 (24 hours after first dose), Day 2 (48 hours after first dose), and Day 3 (72 hours after first dose).
Time frame: Days 1, 2, and 3
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pyronaridine Artesunate | Percentage of Subjects With Parasite Clearance on Days 1, 2, and 3 | Clearance rate (%) at Day 1 (24h after first dose) | 71.6 percentage of subjects |
| Pyronaridine Artesunate | Percentage of Subjects With Parasite Clearance on Days 1, 2, and 3 | Clearance rate (%) at Day 3 (72h after first dose) | 100.0 percentage of subjects |
| Pyronaridine Artesunate | Percentage of Subjects With Parasite Clearance on Days 1, 2, and 3 | Clearance rate (%) at Day 2 (48h after first dose) | 99.5 percentage of subjects |
| Chloroquine | Percentage of Subjects With Parasite Clearance on Days 1, 2, and 3 | Clearance rate (%) at Day 2 (48h after first dose) | 88.0 percentage of subjects |
| Chloroquine | Percentage of Subjects With Parasite Clearance on Days 1, 2, and 3 | Clearance rate (%) at Day 3 (72h after first dose) | 96.7 percentage of subjects |
| Chloroquine | Percentage of Subjects With Parasite Clearance on Days 1, 2, and 3 | Clearance rate (%) at Day 1 (24h after first dose) | 30.6 percentage of subjects |
Other Pre-specified
Percentage of Subjects With Crude and PCR-corrected Cure Rate on Day 42
Cure on Day 42 is defined as the absence of P. vivax parasitaemia on Day 42 irrespective of temperature (axillary, oral, tympanic, rectal) without previously meeting any of the criteria of treatment failure throughout the follow-up period.
Time frame: Day 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pyronaridine Artesunate | Percentage of Subjects With Crude and PCR-corrected Cure Rate on Day 42 | Crude cure rate (%) | 95.5 percentage of subjects |
| Pyronaridine Artesunate | Percentage of Subjects With Crude and PCR-corrected Cure Rate on Day 42 | PCR-corrected cure rate (%) | 95.0 percentage of subjects |
| Chloroquine | Percentage of Subjects With Crude and PCR-corrected Cure Rate on Day 42 | Crude cure rate (%) | 92.1 percentage of subjects |
| Chloroquine | Percentage of Subjects With Crude and PCR-corrected Cure Rate on Day 42 | PCR-corrected cure rate (%) | 94.1 percentage of subjects |
Other Pre-specified
Percentage of Subjects With PCR-corrected Cure Rate on Days 14, 21, and 28
Cure on Days 14, 21, and 28 is defined as the absence of P. vivax parasitaemia on Days 14, 21, and 28 irrespective of temperature (axillary, oral, tympanic, rectal) without previously meeting any of the criteria of treatment failure throughout the follow-up period.
Time frame: Day 14, 21, and 28
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pyronaridine Artesunate | Percentage of Subjects With PCR-corrected Cure Rate on Days 14, 21, and 28 | Cure rate (%) at Day 14 | 100.0 percentage of subjects |
| Pyronaridine Artesunate | Percentage of Subjects With PCR-corrected Cure Rate on Days 14, 21, and 28 | Cure rate (%) at Day 21 | 100.0 percentage of subjects |
| Pyronaridine Artesunate | Percentage of Subjects With PCR-corrected Cure Rate on Days 14, 21, and 28 | Cure rate (%) at Day 28 | 98.1 percentage of subjects |
| Chloroquine | Percentage of Subjects With PCR-corrected Cure Rate on Days 14, 21, and 28 | Cure rate (%) at Day 14 | 99.5 percentage of subjects |
| Chloroquine | Percentage of Subjects With PCR-corrected Cure Rate on Days 14, 21, and 28 | Cure rate (%) at Day 21 | 99.5 percentage of subjects |
| Chloroquine | Percentage of Subjects With PCR-corrected Cure Rate on Days 14, 21, and 28 | Cure rate (%) at Day 28 | 97.9 percentage of subjects |