A Phase 2 interventional study of Pyronaridine-Artesunate in Uncomplicated Plasmodium Falciparum Malaria, sponsored by Medicines for Malaria Venture. Completed at 1 site in Gabon. Open to participants aged 2 Years to 14 Years. Per ClinicalTrials.gov, last updated 2022-05-05.
Sponsored by Medicines for Malaria Venture · Phase 2, Interventional, and Treatment
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.
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.
1,184 studies on the registry are indexed under Malaria; 79 are open to participants now.
This study's enrollment of 60 is below the median of 252 across 937 interventional studies indexed under Malaria.
Browse Malaria studies →Medicines for Malaria Venture is the lead sponsor of 66 studies on the registry; 3 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients presenting with symptoms of acute uncomplicated falciparum malaria with the following inclusion criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Pyronaridine artesunate 6:2 mg/kg. The tablet strength is 48:16 mg oral PA, with the number of tablets depending on body weight.
Drug: Pyronaridine-Artesunate
Pyronaridine artesunate 9:3 mg/kg. The tablet strength is 72:24 mg oral PA, with the number of tablets depending on body weight.
Drug: Pyronaridine-Artesunate
Pyronaridine artesunate 12:4 mg/kg. The tablet strength is 96:32 mg oral PA, with the number of tablets depending on body weight.
Drug: Pyronaridine-Artesunate
Pyronaridine artesunate 9:3 mg/kg. The sachet of granules strength is 60:20 mg PA, with the number of sachets depending on body weight, and is administered as a suspension with water.
Drug: Pyronaridine-Artesunate
Once a day for 3 days
Also known as: Pyramax
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
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
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
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
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
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
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
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
Crude ACPR on Day 14, 28 and 42
The proportion of patients with crude (non-PCR corrected) ACPR.
Time frame: Days 14, 28, 42
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
| Milestone | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Started | 15 | 15 | 15 | 15 |
| Completed | 10 | 8 | 15 | 14 |
| Not completed | 5 | 7 | 0 | 1 |
| Withdrew: Adverse event | 3 | 5 | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 1 | 0 | 0 |
| Withdrew: Protocol violation | 1 | 0 | 0 | 0 |
| Withdrew: Not treated | 1 | 0 | 0 | 0 |
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.
| Participants | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Percentage of Patients With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28 | 11 | 13 | 15 | 14 |
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.
| hours | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Parasite Clearance Time | 16.4 (16.1 to 22.4) | 16.1 (8.3 to 16.4) | 8.1 (8.0 to 16.0) | 8.3 (8.1 to 15.9) |
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.
| Participants | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Treatment success | 11 | 13 | 15 | 14 |
| Treatment failure | 0 | 0 | 0 | 0 |
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.
| hours | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Fever Clearance Time | 8.2 (8.1 to 16.2) | 8.6 (8.1 to 17.2) | 8.2 (8.1 to 16.2) | 8.2 (NA to NA) |
Clearance of asexual parasitaemia within 7 days of initiation of study medication without recrudescence within 14 days.
| Participants | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Number of Patients With PCR-corrected ACPR on Day 14 | 11 | 13 | 15 | 14 |
Zero presence of parasites for 2 consecutive negative readings taken between 8 and 24 hours apart.
| Participants | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Clearance by >0 - 24 hours (Day 1) | 10 | 11 | 14 | 14 |
| Clearance by >24 - 48 hours (Day 2) | 1 | 2 | 1 | 0 |
| Clearance by >48 - 72 hours (Day 3) | 0 | 0 | 0 | 0 |
| Clearance by >72 hours (Day 3 onwards) | 0 | 0 | 0 | 0 |
| No clearance achieved | 0 | 0 | 0 | 0 |
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.
| Participants | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Baseline | 2 | 0 | 1 | 1 |
| >0-24 hours | 3 | 1 | 1 | 1 |
| >24-48 hours | 2 | 0 | 0 | 0 |
| >48-72 hours | 2 | 1 | 0 | 0 |
| >72 hours - Day 7 | 2 | 0 | 1 | 0 |
| >Day 7 - Day 28 | 1 | 0 | 0 | 0 |
| >Day 28 - Day 42 | 0 | 0 | 0 | 0 |
| >Day 42 | 0 | 0 | 0 | 0 |
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.
| Participants | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Clearance by >0 - 24 hours | 3 | 5 | 3 | 1 |
| Clearance by >24 - 48 hours | 0 | 0 | 0 | 0 |
| Clearance by >48 - 72 hours | 0 | 0 | 0 | 0 |
| No clearance achieved | 0 | 0 | 0 | 0 |
The proportion of patients with crude (non-PCR corrected) ACPR.
| Participants | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Day 14 | 11 | 13 | 15 | 14 |
| Day 28 | 11 | 10 | 15 | 14 |
| Day 42 | 7 | 6 | 13 | 12 |
Clearance of asexual parasitaemia within 7 days of initiation of study medication without recrudescence within 42 days.
| Participants | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Number of Patients With PCR-corrected ACPR on Day 42 | 10 | 8 | 15 | 13 |
Collected over 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. Non-serious events are listed at a 1.7% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group A (Tablets) | 0/14 (0%) | 2/14 (14.3%) | 13/14 (92.9%) |
| Group B (Tablets) | 0/15 (0%) | 0/15 (0%) | 11/15 (73.3%) |
| Group C (Tablets) | 0/15 (0%) | 0/15 (0%) | 13/15 (86.7%) |
| Group D (Granules) | 0/15 (0%) | 0/15 (0%) | 12/15 (80%) |
| Event | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Abdominal painGastrointestinal disorders | 1/14 | 0/15 | 0/15 | 0/15 |
| PyrexiaGeneral disorders | 1/14 | 0/15 | 0/15 | 0/15 |
| ParonychiaInfections and infestations | 1/14 | 0/15 | 0/15 | 0/15 |
| Event | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) |
|---|---|---|---|---|
| Plasmodium falciparum infectionInfections and infestations | 1/14 | 6/15 | 2/15 | 2/15 |
| HeadacheNervous system disorders | 5/14 | 1/15 | 2/15 | 1/15 |
| NasopharyngitisInfections and infestations | 2/14 | 0/15 | 3/15 | 5/15 |
| MalariaInfections and infestations | 4/14 | 0/15 | 0/15 | 0/15 |
| VomitingGastrointestinal disorders | 4/14 | 3/15 | 1/15 | 1/15 |
| AscariasisInfections and infestations | 1/14 | 1/15 | 3/15 | 1/15 |
| CoughRespiratory, thoracic and mediastinal disorders | 2/14 | 1/15 | 2/15 | 1/15 |
| AnorexiaMetabolism and nutrition disorders | 2/14 | 0/15 | 0/15 | 1/15 |
| AcarodermatitisInfections and infestations | 0/14 | 0/15 | 2/15 | 1/15 |
| Fungal skin infectionInfections and infestations | 0/14 | 0/15 | 0/15 | 2/15 |
Safety population: all subjects who received at least 1 dose of study drug. Males/Females between ages of 2 and 14 years, with body weight between 10 and 40kg.
| Age, Continuous(years) | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) | Total |
|---|---|---|---|---|---|
| Mean | 5.8 ± 2.19 | 5.9 ± 3.48 | 5.8 ± 2.60 | 4.6 ± 1.96 | 5.5 ± 2.62 |
| Sex: Female, Male(Participants) | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) | Total |
|---|---|---|---|---|---|
| Female | 6 | 7 | 9 | 7 | 29 |
| Male | 8 | 8 | 6 | 8 | 30 |
| Race/Ethnicity, Customized(Participants) | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) | Total |
|---|---|---|---|---|---|
| Black | 14 | 15 | 15 | 15 | 59 |
| Height(cm) | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) | Total |
|---|---|---|---|---|---|
| Mean | 110.4 ± 13.16 | 109.3 ± 18.66 | 111.8 ± 16.08 | 103.3 ± 14.31 | 108.7 ± 15.67 |
| Weight(kg) | Group A (Tablets) | Group B (Tablets) | Group C (Tablets) | Group D (Granules) | Total |
|---|---|---|---|---|---|
| Mean | 18.7 ± 5.54 | 18.8 ± 7.00 | 19.0 ± 6.44 | 16.5 ± 5.15 | 18.2 ± 6.01 |
This study is completed, as verified in May 2022. You cannot join it, but the record below documents what was studied.
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Medicines for Malaria Venture