Uncomplicated Plasmodium Falciparum Malaria
Conditions
Keywords
malaria, P. falciparum, artemisinin based combination therapy (ACT), antimalarial, pyronaridine artesunate (Pyramax)
Brief summary
The purpose of this study is to evaluate three dose levels of a combination tablet and a fixed dose granule formulation of pyronaridine and artesunate (PA) for the treatment of acute uncomplicated falciparum malaria in children.
Detailed description
This is a Phase II, open-label, sequential-group, dose-escalation, single-centre study to study pharmacokinetics, bioavailability comparison of tablets vs. granules, and safety/tolerability of PA in paediatric patients with acute symptomatic uncomplicated P. falciparum malaria. The study population will include 60 patients, comprising male and female children recruited from a single study site located in the endemic region of Gabon. Patients will be assigned sequentially to 1 of 4 treatment groups (15 per group): Group A (Tablets) PA (48 mg + 16 mg), Group B (Tablets) PA (72 mg + 24 mg), Group C (Tablets) PA (96 mg + 32 mg), Group D (Granules) PA (60 mg + 20 mg). Oral tablets will be taken once daily for 3 consecutive days (Days 0, 1 and 2). The dose given to each patient depends on the dosing cohort group and the patient's body weight. Each patient will attend the study site for screening and baseline procedures, as well as receipt of the first dose of study drug on Day 0 (Visit 1, baseline). Patients will be hospitalised for the first 72 hours and remain near the study site for the entire duration of the study. The patients will return to the study site for all scheduled follow-up visits until discharge on Day 42. The primary efficacy end point for the study is the incidence of patients with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28. 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.
Interventions
Once a day for 3 days
Sponsors
Shin Poong Pharmaceuticals
Institute of Tropical Medicine, University of Tuebingen
Medicines for Malaria Venture
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 14 Years
Healthy volunteers
No
Inclusion criteria
Patients presenting with symptoms of acute uncomplicated falciparum malaria with the following inclusion criteria: * Male or female children, being between 2 and 14 years of age inclusive * Weight between 10 and 40 kg inclusive * Written informed consent, in accordance to local practice, provided by parent/guardian. If the parent/guardian is unable to write, witnessed consent is permitted according to local ethical considerations. Where possible, parent assent will be sought * Absence of severe malnutrition (defined as mid upper arm circumference \<110mm) * Presence of acute symptomatic uncomplicated P. falciparum malaria with a diagnosis confirmed by a positive blood smear with asexual forms of P. falciparum only (i.e. no mixed infection) plus measured temperature of ≥37.5°C (depending on method of measurement as below) or history of fever within the past 24 hours : * the acceptable range is between 1,000 and 200,000 asexual parasite count/μl of blood and * axillary/tympanic temperature of ≥37.5°C or oral/rectal temperature of ≥38.0°C * Females of childbearing potential are not allowed to be pregnant or lactating and must be willing to use adequate measures of contraception during the study period * Ability to comply with the study visit schedule and the study protocol for the duration of the study
Exclusion criteria
* Patients with signs and symptoms of severe/complicated malaria requiring parenteral antimalarial treatment according to the WHO Criteria 2000 * Mixed Plasmodium infection * Severe vomiting, defined as \>3 times in the 24 hours prior to inclusion in the study or inability to tolerate oral treatment, or severe diarrhoea defined as \>3 watery stools per day * Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, acute QTc interval greater or equal to 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 head trauma) * Presence of febrile conditions caused by diseases other than malaria * Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or artesunate or other artemisinins * Use of any other antimalarial treatment within 2 weeks prior to start of the study as confirmed by Lignin test and Saker Solomon urine test * For females of childbearing potential, positive urine pregnancy test or lactating * Use of an investigational drug within the past 8 weeks * Known active Hep A immunoglobulin, Hep B surface antigen, or Hep C antibody * Known seropositive HIV antibody * Liver function tests (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] levels) \>3 times the upper limit of normal * Known significant renal impairment as indicated by a serum creatinine ≥2 mg/dL * Previous participation in this clinical study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28 | Day 28 | Clearance of asexual parasitaemia within 7 days of initiation of study medication without recrudescence within 28 days, without previously meeting any of the criteria for early treatment failure, late clinical failure, or late parasitological failure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Success or Failure | Day 28 | Treatment success for the ACPR analysis is defined as the clearance of asexual parasitaemia within 7 days of initiation of study medication without recrudescence within 28 days, without previously meeting any of the criteria for early treatment failure, late clinical failure, or late parasitological failure. Early and late failures are classified according to the WHO Protocol 2005. |
| Fever Clearance Time | Day 3 | The time from first dosing to the first normal reading with fever clearance, defined as 2 consecutive assessments without fever (\<37.5°C) taken between 8 and 24 hours apart. NB: Time to fever clearance was only summarised for subjects who had fever at baseline or within the first 24 hours after the start of study treatment. Since only 12 subjects in total had fever during this time, the time to fever clearance estimates are not very meaningful. |
| Number of Patients With PCR-corrected ACPR on Day 14 | Day 14 | Clearance of asexual parasitaemia within 7 days of initiation of study medication without recrudescence within 14 days. |
| Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Days 1, 2, 3 | Zero presence of parasites for 2 consecutive negative readings taken between 8 and 24 hours apart. |
| Parasite Clearance Time | Day 3 | The time from first dosing to the time of first blood draw with parasite clearance. Parasite clearance is defined as zero presence of parasites for 2 consecutive negative readings taken between 8 and 24 hours apart. |
| Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Days 1, 2, 3 | Patient without fever for 2 consecutive readings taken between 8 and 24 hours apart. NB: Percentage of fever clearance was only summarised for subjects who had fever at baseline or within the first 24 hours after the start of study treatment. Since only 12 subjects in total had fever during this time, the time to fever clearance estimates are not very meaningful. |
| Crude ACPR on Day 14, 28 and 42 | Days 14, 28, 42 | The proportion of patients with crude (non-PCR corrected) ACPR. |
| Number of Patients With PCR-corrected ACPR on Day 42 | Day 42 | Clearance of asexual parasitaemia within 7 days of initiation of study medication without recrudescence within 42 days. |
| Number of Subjects With P. Falciparum Gametocytes During the Trial | Day 42 | The number of gametocytes per μl at Days 0, 3, 7, 14, 21, 28, 35, and 42 summarised from blood slides taken on the respective days. P. falciparum gametocytes are responsible for transmission from host to vector. |
Countries
Gabon
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A (Tablets) Pyronaridine artesunate 6:2 mg/kg | 14 |
| Group B (Tablets) Pyronaridine artesunate 9:3 mg/kg | 15 |
| Group C (Tablets) Pyronaridine artesunate 12:4 mg/kg | 15 |
| Group D (Granules) Pyronaridine artesunate 9:3 mg/kg | 15 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Not treated | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 5.8 years STANDARD_DEVIATION 2.19 | 5.9 years STANDARD_DEVIATION 3.48 | 5.8 years STANDARD_DEVIATION 2.6 | 4.6 years STANDARD_DEVIATION 1.96 | 5.5 years STANDARD_DEVIATION 2.62 |
| Height | 110.4 cm STANDARD_DEVIATION 13.16 | 109.3 cm STANDARD_DEVIATION 18.66 | 111.8 cm STANDARD_DEVIATION 16.08 | 103.3 cm STANDARD_DEVIATION 14.31 | 108.7 cm STANDARD_DEVIATION 15.67 |
| Race/Ethnicity, Customized Black | 14 Participants | 15 Participants | 15 Participants | 15 Participants | 59 Participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 9 Participants | 7 Participants | 29 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 6 Participants | 8 Participants | 30 Participants |
| Weight | 18.7 kg STANDARD_DEVIATION 5.54 | 18.8 kg STANDARD_DEVIATION 7 | 19.0 kg STANDARD_DEVIATION 6.44 | 16.5 kg STANDARD_DEVIATION 5.15 | 18.2 kg STANDARD_DEVIATION 6.01 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 15 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 13 / 14 | 11 / 15 | 13 / 15 | 12 / 15 |
| serious Total, serious adverse events | 2 / 14 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Percentage of Patients With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28
Clearance of asexual parasitaemia within 7 days of initiation of study medication without recrudescence within 28 days, without previously meeting any of the criteria for early treatment failure, late clinical failure, or late parasitological failure.
Time frame: Day 28
Population: Per protocol population: all patients who received a full course of study treatment, had a known status of the primary efficacy variable, and did not have major protocol violations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A (Tablets) | Percentage of Patients With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28 | 11 Participants |
| Group B (Tablets) | Percentage of Patients With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28 | 13 Participants |
| Group C (Tablets) | Percentage of Patients With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28 | 15 Participants |
| Group D (Granules) | Percentage of Patients With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28 | 14 Participants |
Secondary
Crude ACPR on Day 14, 28 and 42
The proportion of patients with crude (non-PCR corrected) ACPR.
Time frame: Days 14, 28, 42
Population: Per protocol population: all patients who received a full course of study treatment, had a known status of the primary efficacy variable, and did not have major protocol violations.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A (Tablets) | Crude ACPR on Day 14, 28 and 42 | Day 42 | 7 Participants |
| Group A (Tablets) | Crude ACPR on Day 14, 28 and 42 | Day 14 | 11 Participants |
| Group A (Tablets) | Crude ACPR on Day 14, 28 and 42 | Day 28 | 11 Participants |
| Group B (Tablets) | Crude ACPR on Day 14, 28 and 42 | Day 28 | 10 Participants |
| Group B (Tablets) | Crude ACPR on Day 14, 28 and 42 | Day 42 | 6 Participants |
| Group B (Tablets) | Crude ACPR on Day 14, 28 and 42 | Day 14 | 13 Participants |
| Group C (Tablets) | Crude ACPR on Day 14, 28 and 42 | Day 28 | 15 Participants |
| Group C (Tablets) | Crude ACPR on Day 14, 28 and 42 | Day 14 | 15 Participants |
| Group C (Tablets) | Crude ACPR on Day 14, 28 and 42 | Day 42 | 13 Participants |
| Group D (Granules) | Crude ACPR on Day 14, 28 and 42 | Day 14 | 14 Participants |
| Group D (Granules) | Crude ACPR on Day 14, 28 and 42 | Day 28 | 14 Participants |
| Group D (Granules) | Crude ACPR on Day 14, 28 and 42 | Day 42 | 12 Participants |
Secondary
Fever Clearance Time
The time from first dosing to the first normal reading with fever clearance, defined as 2 consecutive assessments without fever (\<37.5°C) taken between 8 and 24 hours apart. NB: Time to fever clearance was only summarised for subjects who had fever at baseline or within the first 24 hours after the start of study treatment. Since only 12 subjects in total had fever during this time, the time to fever clearance estimates are not very meaningful.
Time frame: Day 3
Population: Only patients with a fever at baseline or within 24 hours were taken into account.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (Tablets) | Fever Clearance Time | 8.2 hours |
| Group B (Tablets) | Fever Clearance Time | 8.6 hours |
| Group C (Tablets) | Fever Clearance Time | 8.2 hours |
| Group D (Granules) | Fever Clearance Time | 8.2 hours |
Secondary
Number of Patients With Parasite Clearance at Day 1, 2 and 3
Zero presence of parasites for 2 consecutive negative readings taken between 8 and 24 hours apart.
Time frame: Days 1, 2, 3
Population: Per protocol population: all patients who received a full course of study treatment, had a known status of the primary efficacy variable, and did not have major protocol violations.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >72 hours (Day 3 onwards) | 0 Participants |
| Group A (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >24 - 48 hours (Day 2) | 1 Participants |
| Group A (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | No clearance achieved | 0 Participants |
| Group A (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >48 - 72 hours (Day 3) | 0 Participants |
| Group A (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >0 - 24 hours (Day 1) | 10 Participants |
| Group B (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >48 - 72 hours (Day 3) | 0 Participants |
| Group B (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >72 hours (Day 3 onwards) | 0 Participants |
| Group B (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | No clearance achieved | 0 Participants |
| Group B (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >24 - 48 hours (Day 2) | 2 Participants |
| Group B (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >0 - 24 hours (Day 1) | 11 Participants |
| Group C (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >48 - 72 hours (Day 3) | 0 Participants |
| Group C (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >0 - 24 hours (Day 1) | 14 Participants |
| Group C (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >24 - 48 hours (Day 2) | 1 Participants |
| Group C (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >72 hours (Day 3 onwards) | 0 Participants |
| Group C (Tablets) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | No clearance achieved | 0 Participants |
| Group D (Granules) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >72 hours (Day 3 onwards) | 0 Participants |
| Group D (Granules) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >24 - 48 hours (Day 2) | 0 Participants |
| Group D (Granules) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >0 - 24 hours (Day 1) | 14 Participants |
| Group D (Granules) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | Clearance by >48 - 72 hours (Day 3) | 0 Participants |
| Group D (Granules) | Number of Patients With Parasite Clearance at Day 1, 2 and 3 | No clearance achieved | 0 Participants |
Secondary
Number of Patients With PCR-corrected ACPR on Day 14
Clearance of asexual parasitaemia within 7 days of initiation of study medication without recrudescence within 14 days.
Time frame: Day 14
Population: Per protocol population: all patients who received a full course of study treatment, had a known status of the primary efficacy variable, and did not have major protocol violations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A (Tablets) | Number of Patients With PCR-corrected ACPR on Day 14 | 11 Participants |
| Group B (Tablets) | Number of Patients With PCR-corrected ACPR on Day 14 | 13 Participants |
| Group C (Tablets) | Number of Patients With PCR-corrected ACPR on Day 14 | 15 Participants |
| Group D (Granules) | Number of Patients With PCR-corrected ACPR on Day 14 | 14 Participants |
Secondary
Number of Patients With PCR-corrected ACPR on Day 42
Clearance of asexual parasitaemia within 7 days of initiation of study medication without recrudescence within 42 days.
Time frame: Day 42
Population: Per protocol population: all patients who received a full course of study treatment, had a known status of the primary efficacy variable, and did not have major protocol violations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A (Tablets) | Number of Patients With PCR-corrected ACPR on Day 42 | 10 Participants |
| Group B (Tablets) | Number of Patients With PCR-corrected ACPR on Day 42 | 8 Participants |
| Group C (Tablets) | Number of Patients With PCR-corrected ACPR on Day 42 | 15 Participants |
| Group D (Granules) | Number of Patients With PCR-corrected ACPR on Day 42 | 13 Participants |
Secondary
Number of Subjects With P. Falciparum Gametocytes During the Trial
The number of gametocytes per μl at Days 0, 3, 7, 14, 21, 28, 35, and 42 summarised from blood slides taken on the respective days. P. falciparum gametocytes are responsible for transmission from host to vector.
Time frame: Day 42
Population: Per protocol population: all patients who received a full course of study treatment, had a known status of the primary efficacy variable, and did not have major protocol violations.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | Baseline | 2 Participants |
| Group A (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >0-24 hours | 3 Participants |
| Group A (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >24-48 hours | 2 Participants |
| Group A (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >48-72 hours | 2 Participants |
| Group A (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >72 hours - Day 7 | 2 Participants |
| Group A (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >Day 7 - Day 28 | 1 Participants |
| Group A (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >Day 28 - Day 42 | 0 Participants |
| Group A (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >Day 42 | 0 Participants |
| Group B (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >Day 7 - Day 28 | 0 Participants |
| Group B (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >72 hours - Day 7 | 0 Participants |
| Group B (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >0-24 hours | 1 Participants |
| Group B (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >Day 42 | 0 Participants |
| Group B (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >Day 28 - Day 42 | 0 Participants |
| Group B (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >48-72 hours | 1 Participants |
| Group B (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >24-48 hours | 0 Participants |
| Group B (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | Baseline | 0 Participants |
| Group C (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >Day 28 - Day 42 | 0 Participants |
| Group C (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >24-48 hours | 0 Participants |
| Group C (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >48-72 hours | 0 Participants |
| Group C (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >72 hours - Day 7 | 1 Participants |
| Group C (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >Day 7 - Day 28 | 0 Participants |
| Group C (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >Day 42 | 0 Participants |
| Group C (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | Baseline | 1 Participants |
| Group C (Tablets) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >0-24 hours | 1 Participants |
| Group D (Granules) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >24-48 hours | 0 Participants |
| Group D (Granules) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >48-72 hours | 0 Participants |
| Group D (Granules) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >0-24 hours | 1 Participants |
| Group D (Granules) | Number of Subjects With P. Falciparum Gametocytes During the Trial | Baseline | 1 Participants |
| Group D (Granules) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >72 hours - Day 7 | 0 Participants |
| Group D (Granules) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >Day 42 | 0 Participants |
| Group D (Granules) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >Day 28 - Day 42 | 0 Participants |
| Group D (Granules) | Number of Subjects With P. Falciparum Gametocytes During the Trial | >Day 7 - Day 28 | 0 Participants |
Secondary
Parasite Clearance Time
The time from first dosing to the time of first blood draw with parasite clearance. Parasite clearance is defined as zero presence of parasites for 2 consecutive negative readings taken between 8 and 24 hours apart.
Time frame: Day 3
Population: Per protocol population: all patients who received a full course of study treatment, had a known status of the primary efficacy variable, and did not have major protocol violations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (Tablets) | Parasite Clearance Time | 16.4 hours |
| Group B (Tablets) | Parasite Clearance Time | 16.1 hours |
| Group C (Tablets) | Parasite Clearance Time | 8.1 hours |
| Group D (Granules) | Parasite Clearance Time | 8.3 hours |
Secondary
Percentage of Patients With Fever Clearance at Day 1, 2 and 3
Patient without fever for 2 consecutive readings taken between 8 and 24 hours apart. NB: Percentage of fever clearance was only summarised for subjects who had fever at baseline or within the first 24 hours after the start of study treatment. Since only 12 subjects in total had fever during this time, the time to fever clearance estimates are not very meaningful.
Time frame: Days 1, 2, 3
Population: Only patients with a fever at baseline or within 24 hours were taken into account.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A (Tablets) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Clearance by >0 - 24 hours | 3 Participants |
| Group A (Tablets) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Clearance by >24 - 48 hours | 0 Participants |
| Group A (Tablets) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Clearance by >48 - 72 hours | 0 Participants |
| Group A (Tablets) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | No clearance achieved | 0 Participants |
| Group B (Tablets) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Clearance by >24 - 48 hours | 0 Participants |
| Group B (Tablets) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Clearance by >48 - 72 hours | 0 Participants |
| Group B (Tablets) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | No clearance achieved | 0 Participants |
| Group B (Tablets) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Clearance by >0 - 24 hours | 5 Participants |
| Group C (Tablets) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Clearance by >48 - 72 hours | 0 Participants |
| Group C (Tablets) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Clearance by >24 - 48 hours | 0 Participants |
| Group C (Tablets) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | No clearance achieved | 0 Participants |
| Group C (Tablets) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Clearance by >0 - 24 hours | 3 Participants |
| Group D (Granules) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | No clearance achieved | 0 Participants |
| Group D (Granules) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Clearance by >24 - 48 hours | 0 Participants |
| Group D (Granules) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Clearance by >0 - 24 hours | 1 Participants |
| Group D (Granules) | Percentage of Patients With Fever Clearance at Day 1, 2 and 3 | Clearance by >48 - 72 hours | 0 Participants |
Secondary
Treatment Success or Failure
Treatment success for the ACPR analysis is defined as the clearance of asexual parasitaemia within 7 days of initiation of study medication without recrudescence within 28 days, without previously meeting any of the criteria for early treatment failure, late clinical failure, or late parasitological failure. Early and late failures are classified according to the WHO Protocol 2005.
Time frame: Day 28
Population: Per protocol population: all patients who received a full course of study treatment, had a known status of the primary efficacy variable, and did not have major protocol violations.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A (Tablets) | Treatment Success or Failure | Treatment success | 11 Participants |
| Group A (Tablets) | Treatment Success or Failure | Treatment failure | 0 Participants |
| Group B (Tablets) | Treatment Success or Failure | Treatment failure | 0 Participants |
| Group B (Tablets) | Treatment Success or Failure | Treatment success | 13 Participants |
| Group C (Tablets) | Treatment Success or Failure | Treatment success | 15 Participants |
| Group C (Tablets) | Treatment Success or Failure | Treatment failure | 0 Participants |
| Group D (Granules) | Treatment Success or Failure | Treatment success | 14 Participants |
| Group D (Granules) | Treatment Success or Failure | Treatment failure | 0 Participants |