A Phase 2 interventional study of pyronaridine/artesunate in Plasmodium Falciparum Malaria, sponsored by Medicines for Malaria Venture. Completed at 6 sites in 6 countries. Open to participants aged 15 Years to 60 Years. Per ClinicalTrials.gov, last updated 2021-11-02.
Sponsored by Medicines for Malaria Venture · Phase 2, Interventional, and Treatment
The primary trial objective is to determine the clinically effective dose of orally administered pyronaridine/artesunate (Pyramax®, PA) with a 3:1 ratio to treat adults with acute, symptomatic, uncomplicated P. falciparum malaria in South East Asia and Africa. Secondary trial objectives are to determine the safety of once-daily dosing for 3 days of PA and to explore possible ethnic differences in safety or efficacy.
This is a double-blind, multicentre, randomized, parallel group, dose-finding study of the efficacy, safety and tolerability of a once-daily 3-day regimen of PA with a 3:1 weight/weight ratio for patients with acute, symptomatic, uncomplicated P. falciparum malaria. Patients will be recruited from 5 to 7 study sites in endemic regions of South East Asia and Africa and will be randomized to 1 of 3 treatment groups differing in dosage, with 160 patients per group (n-480). Randomization will be balanced within each study site across all 3 study groups in pre-assigned treatment blocks.
The first dose will be administered on Day 0 and patients will remain hospitalized for at least 4 days whilst undertaking the 3-day regimen. Patients will remain near the study site for a minimum of 7 days or once fever and parasite clearance is confirmed (assessed by 3 negative readings of fever and/or slide).
The primary efficacy end point is the cure rate on Day 28 - the proportion of patients with PCR-corrected adequate clinical and parasitological response (ACPR). Despite this Day 28 end point, the relatively long half-life of pyronaridine necessitates follow-up until 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.
455 studies on the registry are indexed under Malaria, Falciparum; 37 are open to participants now.
This study's enrollment of 477 is above the median of 126 across 376 interventional studies indexed under Malaria, Falciparum.
Browse Malaria, Falciparum studies →Medicines for Malaria Venture is the lead sponsor of 66 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
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 history of fever within the previous 24 hours or a measured temperature of ≥37.5°C (depending on method of measurement):
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.
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.
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.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
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.
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.
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.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
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 tetraphosphate 6 mg/kg and artesunate 2 mg/kg
Drug: pyronaridine/artesunate
pyronaridine tetraphosphate 9 mg/kg and artesunate 3 mg/kg
Drug: pyronaridine/artesunate
pyronaridine tetraphsophate 12 mg/kg and artesunate 4 mg/kg
Drug: pyronaridine/artesunate
Tablets of fixed dose combination of pyronaridine and artesunate at a ratio of 3:1. The tablets were taken daily for 3 days.
Also known as: Pyramax
PCR-Corrected ACPR at 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
Time frame: Day 28
PCR-Corrected ACPR at 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
Time frame: Day 14
Parasite Clearance Time
Parasite clearance time was defined as the time (in hours) from first dosing to the time of first blood draw with parasite clearance. Parasite clearance is defined as zero presence of parasites for two consecutive negative readings eight hours apart, with confirmed negative reading at 24 hours after the first negative slide
Time frame: Thick blood slides were examined every 8 hours until at least 72 hours or until a negative smear was recorded
Fever Clearance Time
Fever clearance time was defined as the time (in hours) from first dosing to the first normal reading with fever clearance (2 consecutive assessments without fever (\<37.5°C)). The method of temperature measurement was the same (ie, axillary, tympanic, oral or rectal) for each subject. Any subjects with a documented history of fever at inclusion, but who did not subsequently have a documented temperature reading \>37.5°C during the 24 hours after initial dosing, were not included in this end point analysis.
Time frame: Every 8 hours for at least 72 hours after the first dose
Parasite Clearance
Parasite clearance is defined as zero presence of parasites for 2 consecutive negative readings 8 hours apart, with confirmed negative reading at 24 hours after the first negative slide. The proportion of subjects with parasite clearance was summarized at Days 1, 2, and 3.
Time frame: Days 1, 2, and 3
Fever Clearance
Fever clearance was defined as a subject without fever for 2 consecutive assessments, plus confirmed normal temperature at 24 hours. The proportion of subjects with fever clearance was summarized at Days 1, 2, and 3.
Time frame: Days 1, 2 and 3
Adverse Events (AEs)
An AE was defined as any unfavourable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study
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
| Milestone | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) |
|---|---|---|---|
| Started | 160 | 157 | 160 |
| Completed | 131 | 145 | 146 |
| Not completed | 29 | 12 | 14 |
| Withdrew: Adverse event | 3 | 1 | 1 |
| Withdrew: Withdrawal by subject | 2 | 1 | 1 |
| Withdrew: Lack of efficacy | 7 | 2 | 2 |
| Withdrew: Lost to follow-up | 4 | 3 | 3 |
| Withdrew: Protocol violation | 2 | 1 | 0 |
| Withdrew: No defiined | 11 | 4 | 7 |
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
| percentage of subjects | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) |
|---|---|---|---|
| PCR-Corrected ACPR at Day 28 | 95 (89.9 to 98.0) | 99 (95.5 to 100.0) | 99 (95.4 to 99.9) |
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
| percentage of subjects | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) |
|---|---|---|---|
| PCR-Corrected ACPR at Day 14 | 100 (97.2 to 100.0) | 100 (97.2 to 100.0) | 100 (97.2 to 100.0) |
Parasite clearance time was defined as the time (in hours) from first dosing to the time of first blood draw with parasite clearance. Parasite clearance is defined as zero presence of parasites for two consecutive negative readings eight hours apart, with confirmed negative reading at 24 hours after the first negative slide
| hours | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) |
|---|---|---|---|
| Parasite Clearance Time | 36.9 ± 20.73 | 33.6 ± 17.08 | 30.8 ± 14.96 |
Fever clearance time was defined as the time (in hours) from first dosing to the first normal reading with fever clearance (2 consecutive assessments without fever (\<37.5°C)). The method of temperature measurement was the same (ie, axillary, tympanic, oral or rectal) for each subject. Any subjects with a documented history of fever at inclusion, but who did not subsequently have a documented temperature reading \>37.5°C during the 24 hours after initial dosing, were not included in this end point analysis.
| hours | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) |
|---|---|---|---|
| Fever Clearance Time | 16.8 ± 12.75 | 24.0 ± 25.99 | 17.0 ± 12.90 |
Parasite clearance is defined as zero presence of parasites for 2 consecutive negative readings 8 hours apart, with confirmed negative reading at 24 hours after the first negative slide. The proportion of subjects with parasite clearance was summarized at Days 1, 2, and 3.
| percentage of subjects | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) |
|---|---|---|---|
| Clearance rate (%) at Day 1 (24h after first dose) | 74 (64.8 to 82.0) | 82 (73.1 to 88.4) | 84 (76.2 to 90.6) |
| Clearance rate (%) at Day 2 (48h after first dose) | 93 (85.9 to 96.7) | 96 (90.9 to 99.0) | 95 (89.6 to 98.5) |
| Clearance rate (%) at Day 3 (72h after first dose) | 96 (90.8 to 99.0) | 98 (93.5 to 99.8) | 99 (95.0 to 100.0) |
Fever clearance was defined as a subject without fever for 2 consecutive assessments, plus confirmed normal temperature at 24 hours. The proportion of subjects with fever clearance was summarized at Days 1, 2, and 3.
| percentage of subjects | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) |
|---|---|---|---|
| Clearance rate (%) at Day 1 (24h after first dose) | 96 (90.8 to 99.0) | 91 (83.8 to 95.5) | 96 (90.9 to 99.0) |
| Clearance rate (%) at Day 2 (48h after first dose) | 99 (94.9 to 100.0) | 96 (90.9 to 99.0) | 100 (96.7 to 100.0) |
| Clearance rate (%) at Day 3 (72h after first dose) | 99 (94.9 to 100.0) | 96 (90.9 to 99.0) | 100 (96.7 to 100.0) |
An AE was defined as any unfavourable and unintended sign, symptom, syndrome, or illness that developed or worsened during the period of observation in the clinical study
| Participants | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) |
|---|---|---|---|
| Nr subj. with ≥1 AE | 106 | 90 | 91 |
| Nr subj. with ≥1 treatment-related AE | 35 | 33 | 36 |
| Nr subj. with ≥1 SAE | 3 | 0 | 1 |
| Nr subj. with ≥1 treatment-related SAE | 0 | 0 | 1 |
| Nr subj. with ≥1 AE leading to death | 0 | 0 | 0 |
| Nr subj. with ≥1 AE leading to study withdrawal | 3 | 1 | 1 |
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% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group A: Pyronaridine/Artesunate (6:2 mg/kg) | 0/160 (0%) | 3/160 (1.9%) | 106/160 (66.3%) |
| Group B: Pyronaridine/Artesunate (9:3 mg/kg) | 0/157 (0%) | 0/157 (0%) | 90/157 (57.3%) |
| Group C: Pyronaridine/Artesunate (12:4 mg/kg) | 0/159 (0%) | 1/159 (0.6%) | 91/159 (57.2%) |
| Event | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) |
|---|---|---|---|
| Urinary tract infectionInfections and infestations | 0/160 | 0/157 | 1/159 |
| Hepatic enzyme increasedInvestigations | 0/160 | 0/157 | 1/159 |
| Abortion incompletePregnancy, puerperium and perinatal conditions | 0/160 | 0/157 | 1/159 |
| Cardiac failureCardiac disorders | 1/160 | 0/157 | 0/159 |
| Abscess LimbInfections and infestations | 1/160 | 0/157 | 0/159 |
| MalariaInfections and infestations | 1/160 | 0/157 | 0/159 |
| Event | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) |
|---|---|---|---|
| HeadacheNervous system disorders | 22/160 | 19/157 | 17/159 |
| Eosinophil count increasedInvestigations | 17/160 | 14/157 | 14/159 |
| AnaemiaBlood and lymphatic system disorders | 16/160 | 15/157 | 13/159 |
| CoughRespiratory, thoracic and mediastinal disorders | 13/160 | 7/157 | 13/159 |
| VomitingGastrointestinal disorders | 12/160 | 8/157 | 8/159 |
| MalariaInfections and infestations | 12/160 | 8/157 | 7/159 |
| BradycardiaCardiac disorders | 10/160 | 7/157 | 8/159 |
| MyalgiaMusculoskeletal and connective tissue disorders | 5/160 | 8/157 | 4/159 |
| Abdominal painGastrointestinal disorders | 8/160 | 6/157 | 4/159 |
| EosinophiliaBlood and lymphatic system disorders | 6/160 | 7/157 | 5/159 |
| Age, Continuous(years) | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) | Total |
|---|---|---|---|---|
| Mean | 27.0 ± 10.9 | 27.4 ± 10.9 | 28.9 ± 11.4 | 27.8 ± 11.1 |
| Sex: Female, Male(Participants) | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) | Total |
|---|---|---|---|---|
| Female | 43 | 37 | 40 | 120 |
| Male | 117 | 120 | 119 | 356 |
| Race/Ethnicity, Customized(Participants) | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) | Total |
|---|---|---|---|---|
| White/Caucasian | 0 | 0 | 0 | 0 |
| Black | 49 | 47 | 48 | 144 |
| Asian/Oriental | 111 | 110 | 111 | 332 |
| Region of Enrollment(participants) | Group A: Pyronaridine/Artesunate (6:2 mg/kg) | Group B: Pyronaridine/Artesunate (9:3 mg/kg) | Group C: Pyronaridine/Artesunate (12:4 mg/kg) | Total |
|---|---|---|---|---|
| Cambodia | 10 | 9 | 10 | 29 |
| Senegal | 32 | 32 | 30 | 94 |
| Gambia | 12 | 10 | 13 | 35 |
| Uganda | 5 | 5 | 6 | 16 |
| Thailand | 80 | 80 | 80 | 160 |
| Indonesia | 21 | 21 | 21 | 63 |
The record gives a start of Jul 2005, a primary completion of Mar 2006 and a completion of Apr 2006. It does not say whether these dates are actual or estimated.
Results were first posted in Sep 2021, 15 years 6 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Oct 2021. You cannot join it, but the record below documents what was studied.
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Medicines for Malaria Venture