A Phase 3 interventional study of Pyronaridine artesunate and Coartem® (artemether lumefantrine) in Malaria, sponsored by Medicines for Malaria Venture. Completed at 10 sites in 9 countries. Open to participants aged 3 Years to 60 Years. Per ClinicalTrials.gov, last updated 2021-11-02.
Sponsored by Medicines for Malaria Venture · Phase 3, Interventional, and Treatment
The primary objective of this phase III study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) with that of Coartem® (artemether lumefantrine, AL) in children and adults with uncomplicated P falciparum malaria in Africa and South East Asia.
This is a multi-centre, comparative, randomised, (double-blind, double-dummy), parallel-group, non-inferiority study comparing the efficacy and safety of the fixed combination of PA with that of AL in the treatment of acute, uncomplicated P. falciparum malaria. The study population will include 1269 patients, comprising male and female children (≥20 kg body weight) and adults recruited from study sites in Africa and South East Asia.
Patients will be randomised to receive either oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Days 0, 1, and 2) or AL twice a day plus PA-placebo (once a day) for 3 consecutive days (Days 0, 1, and 2) in a 2:1 ratio. The dose range of PA covered by this regimen is 7.2:2.4 mg/kg to 13.8:4.6 mg/kg, respectively, which has been shown to be effective and safe in Phase I and II studies. Posology will be based on body weight ranges for both the PA and AL regimens.
Patients will be confined to the study facility for ≥4 days (Days 0, 1, 2, and 3) and remain near the study site for ≥7 days, or once fever and parasite clearance has been confirmed for ≥24 hours - whichever occurs later.
The primary efficacy end point for the study is the proportion of patients with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28. Scheduled follow-up visits will continue until completion of the study at Day 42. In the case of adverse events reported and unresolved at Day 42, patients will be followed up for a further 30 days, or until resolution of the event.
1,184 studies on the registry are indexed under Malaria; 79 are open to participants now.
This study's enrollment of 1,272 is above 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.
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 uncomplicated P. falciparum mono-infection confirmed by:
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 protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
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.
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.
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 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.
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.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
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.
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.
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.
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.
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 (PA)
Drug: Pyronaridine artesunate
Arthemether lumefantrine (AL)
Drug: Coartem® (artemether lumefantrine)
Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)
Also known as: Pyramax
AL (20:120mg tablets) twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
Also known as: Coartem
PCR-Corrected Adequate Clinical and Parasitological Response (ACPR) Rate on 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 Adequate Clinical and Parasitological Response (ACPR) on 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
Crude ACPR (Non-PCR Corrected ACPR) on Day 14 and Day 28
Percentage of subjects with adequate clinical and parasitological response (ACPR) on Day 28, without correction by PCR, defined as absence of parasitaemia on Day 28 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure.
Time frame: Day 14 and 28
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, 3, 7, 14, 21, 28, 35, and 42 (or on any other day if the subject spontaneously returned)
Fever Clearance Time
Fever clearance time is defined as the time from first dosing to first normal reading of temperature for 2 consecutive normal temperature readings taken between 7 and 25 hours apart
Time frame: Day 0 and every 8 hours over ≥72 hours following first study drug administration or temperature normalization for ≥2 readings between 7 and 25 hours apart, then at each visit and as clinically indicated
Percentage of Patients With Fever Clearance at Day 1, 2 and 3
Fever clearance time is defined as the time from first dosing to first normal reading of temperature for 2 consecutive normal temperature readings taken between 7 and 25 hours apart.
Time frame: Days 1, 2, 3
Proportion of Patients With Parasite Clearance at Day 1, 2 and 3
Parasite clearance time is defined as the time from first dosing to the time of first blood draw with parasite clearance. Parasite clearance was defined as zero presence of asexual parasites for 2 consecutive negative readings taken between 7 and 25 hours apart.
Time frame: Days 1, 2, 3
Adverse Events and Clinically Significant Laboratory Results
Incidence of adverse events and of clinically significant laboratory results, ECG, vital signs or physical examination abnormalities.
Time frame: Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study or resolution of the event, whichever was earlier
| Milestone | PA Group | AL Group |
|---|---|---|
| Started | 849 | 423 |
| Completed | 751 | 347 |
| Not completed | 98 | 76 |
| Withdrew: Adverse event | 21 | 7 |
| Withdrew: Withdrawal by subject | 12 | 9 |
| Withdrew: Lost to follow-up | 14 | 9 |
| Withdrew: Protocol violation | 4 | 1 |
| Withdrew: Lack of efficacy | 40 | 42 |
| Withdrew: P. vivax infection | 3 | 6 |
| Withdrew: Cyesis | 1 | 0 |
| Withdrew: Withdrawn from study accidentally | 1 | 0 |
| Withdrew: Non-compliance | 1 | 0 |
| Withdrew: Re-location | 0 | 1 |
| Withdrew: Not defined | 1 | 1 |
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 | PA Group | AL Group |
|---|---|---|
| PCR-Corrected Adequate Clinical and Parasitological Response (ACPR) Rate on Day 28 | 99.5 (98.7 to 99.9) | 99.2 (97.7 to 99.8) |
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 | PA Group | AL Group |
|---|---|---|
| PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 14 | 99.9 (99.3 to 100.0) | 100 (99.0 to 100.0) |
Percentage of subjects with adequate clinical and parasitological response (ACPR) on Day 28, without correction by PCR, defined as absence of parasitaemia on Day 28 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure.
| percentage of subjects | PA Group | AL Group |
|---|---|---|
| Cure rate (%) at Day 14 | 100 (99.5 to 100.0) | 100 (99.0 to 100.0) |
| Cure rate (%) at Day 28 | 98.9 (97.8 to 99.5) | 97.2 (95.0 to 98.6) |
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.
| hours | PA Group | AL Group |
|---|---|---|
| Parasite Clearance Time | 23.9 (23.9 to 23.9) | 24.0 (23.9 to 24.1) |
Fever clearance time is defined as the time from first dosing to first normal reading of temperature for 2 consecutive normal temperature readings taken between 7 and 25 hours apart
| hours | PA Group | AL Group |
|---|---|---|
| Fever Clearance Time | 7.9 (7.9 to 8.0) | 8.0 (7.9 to 15.5) |
Fever clearance time is defined as the time from first dosing to first normal reading of temperature for 2 consecutive normal temperature readings taken between 7 and 25 hours apart.
| percentage of subjects | PA Group | AL Group |
|---|---|---|
| Clearance rate (%) at Day 1 (24h after first dose) | 88.7 (86.0 to 91.1) | 87.0 (82.9 to 90.5) |
| Clearance rate (%) at Day 2 (48h after first dose) | 99.0 (97.9 to 99.6) | 98.7 (96.8 to 99.6) |
| Clearance rate (%) at Day 3 (72h after first dose) | 99.5 (98.6 to 99.9) | 99.3 (97.8 to 99.9) |
Parasite clearance time is defined as the time from first dosing to the time of first blood draw with parasite clearance. Parasite clearance was defined as zero presence of asexual parasites for 2 consecutive negative readings taken between 7 and 25 hours apart.
| percentage of subjects | PA Group | AL Group |
|---|---|---|
| Clearance rate (%) at Day 1 (24h after first dose) | 68.1 (64.8 to 71.3) | 52.8 (48.0 to 57.9) |
| Clearance rate (%) at Day 2 (48h after first dose) | 98.1 (96.9 to 98.9) | 97.2 (95.1 to 98.5) |
| Clearance rate (%) at Day 3 (72h after first dose) | 99.5 (98.8 to 99.8) | 99.7 (98.6 to 100) |
Incidence of adverse events and of clinically significant laboratory results, ECG, vital signs or physical examination abnormalities.
| Participants | PA Group | AL Group |
|---|---|---|
| Nr subj. with ≥1 AE | 509 | 241 |
| Nr subj. with ≥1 treatment-related AE | 275 | 123 |
| Nr subj. with ≥1 SAE | 3 | 2 |
| Nr pat with ≥1 treatment-related SAE | 0 | 0 |
| Nr subj. with ≥1 severe or life-threatening AE | 10 | 5 |
| Nr subj. with ≥1 AE leading to death | 0 | 0 |
| Nr subj. ≥1 AE leading to drug discontinuation | 16 | 5 |
| Nr subj. with ≥1 AE leading to study withdrawal | 19 | 6 |
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 |
|---|---|---|---|
| PA Group | 0/849 (0%) | 3/849 (0.4%) | 506/849 (59.6%) |
| AL Group | 0/423 (0%) | 2/423 (0.5%) | 239/423 (56.5%) |
| Event | PA Group | AL Group |
|---|---|---|
| Cerebral malariaInfections and infestations | 0/849 | 1/423 |
| ImmunosuppressionImmune system disorders | 0/849 | 1/423 |
| ParotitisInfections and infestations | 1/849 | 0/423 |
| Typhoid feverInfections and infestations | 1/849 | 0/423 |
| Urinary tract infectionInfections and infestations | 1/849 | 0/423 |
| Event | PA Group | AL Group |
|---|---|---|
| HeadacheNervous system disorders | 71/849 | 41/423 |
| EosinophiliaBlood and lymphatic system disorders | 60/849 | 26/423 |
| NeutropeniaBlood and lymphatic system disorders | 41/849 | 27/423 |
| CoughRespiratory, thoracic and mediastinal disorders | 49/849 | 27/423 |
| Abdominal painGastrointestinal disorders | 50/849 | 23/423 |
| VomitingGastrointestinal disorders | 42/849 | 15/423 |
| LymphocytosisBlood and lymphatic system disorders | 21/849 | 16/423 |
| Upper respiratoty tract infectionInfections and infestations | 32/849 | 12/423 |
| Influenza like illnessGeneral disorders | 30/849 | 13/423 |
| Aspartate aminotransferase increasedInvestigations | 21/849 | 6/423 |
Intent-to-treat (ITT) population, defined as all randomized subjects who received any amount of study medication. Subjects were analyzed as randomized.
| Age, Continuous(years) | PA Group | AL Group | Total |
|---|---|---|---|
| Mean | 17.2 ± 11.12 | 18.0 ± 11.41 | 17.5 ± 11.22 |
| Sex: Female, Male(Participants) | PA Group | AL Group | Total |
|---|---|---|---|
| Female | 359 | 192 | 551 |
| Male | 490 | 231 | 721 |
| Race/Ethnicity, Customized(Participants) | PA Group | AL Group | Total |
|---|---|---|---|
| Black | 722 | 358 | 1080 |
| Asian/Oriental | 127 | 65 | 192 |
| Region of Enrollment(participants) | PA Group | AL Group | Total |
|---|---|---|---|
| Mozambique | 89 | 44 | 133 |
| Gambia | 72 | 34 | 106 |
| Mali | 132 | 66 | 198 |
| Senegal | 138 | 68 | 206 |
| Philippines | 67 | 36 | 103 |
| Congo, The Democratic Republic of the | 199 | 99 | 298 |
| Ghana | 4 | 3 | 7 |
| Kenya | 88 | 44 | 132 |
| Indonesia | 60 | 29 | 89 |
The record gives a start of Jan 2007, a primary completion of Apr 2008 and a completion of May 2008. It does not say whether these dates are actual or estimated.
Results were first posted in Sep 2021, 13 years 5 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.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Medicines for Malaria Venture