A Phase 2 interventional study of M5717 330 mg and M5717 500 mg in Acute Malaria, sponsored by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany. Completed at 5 sites in 4 countries. Open to participants aged 12 Years to 55 Years. Per ClinicalTrials.gov, last updated 2025-08-27.
Sponsored by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany (part of Merck KGaA, Darmstadt, Germany) · Phase 2, Interventional, and Treatment
The purpose of this study was to evaluate the safety, efficacy, and pharmacokinetic of the combination M5717 plus pyronaridine in participants with acute uncomplicated Plasmodium falciparum malaria.
455 studies on the registry are indexed under Malaria, Falciparum; 37 are open to participants now.
This study's enrollment of 38 is below the median of 126 across 376 interventional studies indexed under Malaria, Falciparum.
Browse Malaria, Falciparum studies →Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany is the lead sponsor of 55 studies on the registry; 4 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
M5717 and pyronaridine once daily in a single day treatment regimen at low dose of 330 milligrams (mg) and 360 mg respectively.
Drug: M5717 330 mg · Drug: Pyronaridine 360 mg
After completion of Part A, if dose will be considered safe and well tolerated, the Internal Data Monitoring Committee (IDMC) will have the option to recommend dose adjustments. M5717 and pyronaridine once daily will be administered in an escalated dose in a single day or 2-day treatment regimen.
Drug: M5717 500 mg · Drug: M5717 660 mg · Drug: Pyronaridine 360 mg · Drug: Pyronaridine 540 mg · Drug: Pyronaridine 720 mg
Participants will receive orally 330 mg granules of M5717 in combination with pyronaridine dispersed in water under fasting condition.
Adolescent participants with weight less than (\<) 45 kilograms (kg) will receive orally 500 mg granules of M5717 in combination with pyronaridine dispersed in water once daily under fasting condition.
Adult and adolescent participants with weight more than or equal to (\>=) 45 kg will receive orally 660 mg granules of M5717 in combination with pyronaridine dispersed in water once daily under fasting condition.
Participants will receive 360 mg of pyronaridine tablets in combination with M5717 under fasting condition.
Participants with weight \>=24 to \<45 kg will receive 360 mg of tablets in combination with M5717 under fasting condition.
Participants with weight \>=45 to \<65 kg will receive 540 mg of Pyronaridine tablets in combination with M5717 under fasting condition.
Participants with weight \>=65 kg will receive 720 mg of Pyronaridine tablets in combination with M5717 under fasting condition.
Cohort A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs
An adverse event (AE) was defined as any untoward medical occurrence in a participant. TEAEs are defined as AEs which started at or after the administration of study intervention (study treatment) or which started prior to the first administration of study intervention but worsened after the dose intake, until the last scheduled assessment will be regarded as treatment-emergent, but before established rescue antimalarial treatment is administered, if required. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was considered to be "related" if a causal relationship between study treatment and the TEAE is at least reasonably possible.
Time frame: Day 1 up to Day 43
Cohort A: Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Parameters
Number of participants with clinically significant change from baseline in laboratory parameters were reported. Clinical Significance was decided by the investigator. Laboratory investigation included hematology, biochemistry, and coagulation.
Time frame: Day 1 up to Day 29
Cohort A: Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
Number of participants with clinically significant change from baseline in ECG parameters were reported. Clinical Significance was decided by the investigator. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), Respiratory Rate, Pulse Rate, QRS, QT and QTcB calculated by the Bazett formula.
Time frame: Day 1 up to Day 29
Cohort A: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Number of participants with clinically significant change from baseline in vital signs. Clinical Significance was decided by the investigator. Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate.
Time frame: Day 1 up to Day 29
Cohort B0: Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
PCR-adjusted ACPR 28 days after first treatment (i.e., on Day 29) was defined as absence of parasitemia (thick smear/microscopy, after adjustment for parasitemia due to new infections as determined by genotyping using PCR techniques), irrespective of axillary temperature, in participants who did not previously meet any of the criteria of Early treatment failure (ETF), Late clinical failure (LCF), or Late parasitological failure (LPF).
Time frame: At Day 29
Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 and Pyronaridine
The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination. Calculated as AUC0-inf = AUC0-tlast + Clast pred/ lambda z.
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717 and Pyronaridine
The AUC from time zero (dosing time) to 24 hours post dose was calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval.
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) of M5717 and Pyronaridine
The AUC from time zero (= dosing time) to the time of the last quantifiable concentration (tlast), calculated using the mixed log linear trapezoidal rule (linear up, log down)
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Apparent Total Clearance (CL/F) of M5717 and Pyronaridine
The apparent total body clearance of study intervention following extravascular administration. CL/ F was calculated by oral dose divided by Area under the plasma concentration curve 0- infinity.
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Maximum Plasma Concentration (Cmax) of M5717 and Pyronaridine
Cmax was taken directly from the observed concentration-time curve.
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Apparent Terminal Half-Life of M5717 and Pyronaridine
t1/2 was the time measured for the concentration to decrease by one half. t1/2 was calculated by natural log 2 divided by Lambda z.
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Time to Reach Maximum Plasma Concentration (Tmax) of M5717 and Pyronaridine
tmax was obtained directly from the concentration versus time curve.
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Apparent Volume of Distribution (Vz/F) of M5717 and Pyronaridine
The apparent volume of distribution during the terminal phase following extravascular administration. Vz/F = Dose/(AUC0-∞\*λz) following single dose.
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Dose Normalized Area Under the Curve From Time Zero to 24 Hours Post Dose (AUC0-24h/Dose) of M5717 and Pyronaridine
The dose normalized AUC from time zero to 24 hours post dose. Normalized using the dose, using the formula AUC0-24/Dose.
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Dose Normalized Area Under the Curve From Time Zero to the Last Sampling Time (AUC0-tlast/Dose) of M5717 and Pyronaridine
The dose normalized AUC from time zero to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Normalized using the dose, using the formula AUC0-tlast /Dose.
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Dose Normalized Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-∞/Dose) of M5717 and Pyronaridine
The dose normalized AUC from time zero extrapolated to infinity. Normalized using dose, using the formula AUC0-∞ /Dose.
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Terminal Elimination Rate Constant (Lambda z) of M5717 and Pyronaridine
Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Dose Normalized Maximum Concentration (Cmax/Dose) of M5717 and Pyronaridine
The dose normalized maximum concentration. Normalized using the dose, and the formula Cmax /Dose.
Time frame: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43
Cohort A and Cohort B0: Percentage of Participants With Early Treatment Failure (ETF)
Early treatment failure (ETF) was defined as meeting any of the following : 1. Danger signs or severe malaria 1, 2, or 3 days after treatment, in the presence of parasitemia2. Parasitemia 2 days after treatment higher than on day of treatment, irrespective of axillary temperature • Parasitemia 3 days after treatment with temperature ≥ 37.5°C 3. Parasitemia 3 days after treatment ≥ 25% of count on day of treatment. ETF rate will be estimated with 95% confidence intervals. Confidence intervals was derived by use of Wilson's score method.
Time frame: Up to Day 3 post treatment on Day 1
Cohort A and Cohort B0: Percentage of Participants With Late Clinical Failure (LCF)
Late clinical failure (LCF) was defined as:1. Danger signs or severe malaria in the presence of parasitemia on any day between 4 and 28 days after treatment (i.e., between Days 5 and 29) in participants who did not previously meet any of the criteria of ETF. 2. Presence of parasitemia on any day between 4 and 28 days after treatment with temperature ≥ 37.5°C in participants who did not previously meet any of the criteria of ETF. LCF was estimated with 95% confidence intervals. Confidence intervals will be derived by use of Wilson's score method.
Time frame: Day 1 up to Day 29
Cohort A and Cohort B0: Percentage of Participants With Late Parasitological Failure (LPF)
Late parasitological failure (LPF) was defined as: Presence of parasitemia on any day between 7 and 28 days after treatment (i.e., between Days 8 and 29) with temperature \< 37.5°C in participants who did not previously meet any of the criteria of ETF or LCF. LPF was estimated with 95% confidence intervals. Confidence intervals will be derived by use of Wilson's score method.
Time frame: From Day 8 to Day 29
Cohort A: Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)
PCR-adjusted ACPR 28 and 42 days after treatment defined as absence of parasitemia (thick smear/microscopy, after adjustment for parasitemia due to new infections as determined by genotyping using PCR techniques), irrespective of axillary temperature, in participants who did not previously meet any of the criteria of ETF, LCF, or LPF.
Time frame: Day 28 and 42
Cohort A and B0: Percentage of Participants With Crude Adequate Clinical and Parasitological Response (ACPR)
Crude ACPR 28 and 42 days after first dose is defined as absence of parasitemia (parasite count = 0) from thick smear/microscopy, irrespective of axillary temperature, in participants who did not previously meet any of the criteria of ETF, LCF, or LPF.
Time frame: Day 28 and 42
Cohort A and Cohort B0: Time to Fever Clearance as Estimated by Kaplan-Meier Method
Fever clearance time was defined as the time from first dosing to the first measurement of temperature \< 37.5°C for 2 consecutive temperature readings plus confirmed normal temperature 24 h after the first normal body temperature reading. This analysis was done on participants with fever.
Time frame: Day 1 up to Day 29
Cohort A and Cohort B0: Parasite Clearance Time as Estimated by Kaplan-Meier Method
Parasite clearance time defined as time from dosing to the first negative (no parasites) film
Time frame: Day 1 up to Day 43
Cohort B0: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs
An adverse event (AE) was defined as any untoward medical occurrence in a participant. TEAEs are defined as AEs which started at or after the administration of study intervention (study treatment) or which started prior to the first administration of study intervention but worsened after the dose intake, until the last scheduled assessment will be regarded as treatment-emergent, but before established rescue antimalarial treatment is administered, if required. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was considered to be "related" if a causal relationship between study treatment and the TEAE is at least reasonably possible.
Time frame: Day 1 up to Day 43
| Milestone | Cohort A: M5717+Pyronaridine | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine |
|---|---|---|
| Started | 12 | 26 |
| Completed | 11 | 25 |
| Not completed | 1 | 1 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Protocol deviation | 1 | 0 |
An adverse event (AE) was defined as any untoward medical occurrence in a participant. TEAEs are defined as AEs which started at or after the administration of study intervention (study treatment) or which started prior to the first administration of study intervention but worsened after the dose intake, until the last scheduled assessment will be regarded as treatment-emergent, but before established rescue antimalarial treatment is administered, if required. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was considered to be "related" if a causal relationship between study treatment and the TEAE is at least reasonably possible.
| Participants | Cohort A: M5717+Pyronaridine |
|---|---|
| TEAEs | 9 |
| Serious TEAEs | 0 |
| Related TEAEs | 1 |
Number of participants with clinically significant change from baseline in laboratory parameters were reported. Clinical Significance was decided by the investigator. Laboratory investigation included hematology, biochemistry, and coagulation.
| Participants | Cohort A: M5717+Pyronaridine |
|---|---|
| Cohort A: Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Parameters | 0 |
Number of participants with clinically significant change from baseline in ECG parameters were reported. Clinical Significance was decided by the investigator. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), Respiratory Rate, Pulse Rate, QRS, QT and QTcB calculated by the Bazett formula.
| Participants | Cohort A: M5717+Pyronaridine |
|---|---|
| Cohort A: Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 |
Number of participants with clinically significant change from baseline in vital signs. Clinical Significance was decided by the investigator. Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate.
| Participants | Cohort A: M5717+Pyronaridine |
|---|---|
| Cohort A: Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 |
PCR-adjusted ACPR 28 days after first treatment (i.e., on Day 29) was defined as absence of parasitemia (thick smear/microscopy, after adjustment for parasitemia due to new infections as determined by genotyping using PCR techniques), irrespective of axillary temperature, in participants who did not previously meet any of the criteria of Early treatment failure (ETF), Late clinical failure (LCF), or Late parasitological failure (LPF).
| percentage of participants | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine |
|---|---|
| Cohort B0: Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) | 92.3 (75.9 to 97.9) |
The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination. Calculated as AUC0-inf = AUC0-tlast + Clast pred/ lambda z.
| hour*nanogram/milliliter(h*ng/ml) | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 and Pyronaridine | 11194.723 ± 0.238 | 33307.278 ± 0.153 | 33756.087 ± 0.384 | 4397.819 ± 0.590 | 8557.596 ± 0.347 | 5899.378 ± 0.289 |
The AUC from time zero (dosing time) to 24 hours post dose was calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval.
| h*ng/ml | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717 and Pyronaridine | 3663.092 ± 0.373 | 13063.782 ± 0.127 | 12038.002 ± 0.393 | 1206.579 ± 0.417 | 2113.426 ± 0.399 | 1603.917 ± 0.197 |
The AUC from time zero (= dosing time) to the time of the last quantifiable concentration (tlast), calculated using the mixed log linear trapezoidal rule (linear up, log down)
| h*ng/ml | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) of M5717 and Pyronaridine | 9877.195 ± 0.455 | 32747.057 ± 0.153 | 33275.071 ± 0.391 | 4397.819 ± 0.590 | 8557.596 ± 0.347 | 5899.378 ± 0.289 |
The apparent total body clearance of study intervention following extravascular administration. CL/ F was calculated by oral dose divided by Area under the plasma concentration curve 0- infinity.
| Liters/hour (l/h) | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Apparent Total Clearance (CL/F) of M5717 and Pyronaridine | 29.478 ± 0.238 | 15.012 ± 0.153 | 19.552 ± 0.384 | 81.859 ± 0.590 | 63.102 ± 0.347 | 122.047 ± 0.289 |
Cmax was taken directly from the observed concentration-time curve.
| ng/ml | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Maximum Plasma Concentration (Cmax) of M5717 and Pyronaridine | 269.358 ± 0.483 | 956.145 ± 0.173 | 991.144 ± 0.385 | 125.600 ± 44.565 | 191.000 ± 78.773 | 138.000 ± 15.122 |
t1/2 was the time measured for the concentration to decrease by one half. t1/2 was calculated by natural log 2 divided by Lambda z.
| hours (h) | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Apparent Terminal Half-Life of M5717 and Pyronaridine | 74.523 ± 0.264 | 65.638 ± 0.152 | 84.202 ± 0.325 | 174.918 ± 0.599 | 228.509 ± 0.233 | 229.264 ± 0.314 |
tmax was obtained directly from the concentration versus time curve.
| hours | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Time to Reach Maximum Plasma Concentration (Tmax) of M5717 and Pyronaridine | 3.179 ± 0.480 | 2.784 ± 0.385 | 3.196 ± 0.508 | 2.778 ± 0.325 | 3.394 ± 0.599 | 4.444 ± 0.767 |
The apparent volume of distribution during the terminal phase following extravascular administration. Vz/F = Dose/(AUC0-∞\*λz) following single dose.
| liters (l) | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Apparent Volume of Distribution (Vz/F) of M5717 and Pyronaridine | 3169.306 ± 0.389 | 1421.536 ± 0.220 | 2375.135 ± 0.647 | 20657.284 ± 0.459 | 20802.718 ± 0.250 | 40368.007 ± 0.224 |
The dose normalized AUC from time zero to 24 hours post dose. Normalized using the dose, using the formula AUC0-24/Dose.
| h*ng/mL/mg | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Dose Normalized Area Under the Curve From Time Zero to 24 Hours Post Dose (AUC0-24h/Dose) of M5717 and Pyronaridine | 11.100 ± 0.373 | 26.128 ± 0.127 | 18.239 ± 0.393 | 3.352 ± 0.417 | 3.914 ± 0.399 | 2.228 ± 0.197 |
The dose normalized AUC from time zero to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Normalized using the dose, using the formula AUC0-tlast /Dose.
| h*ng/mL/mg | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Dose Normalized Area Under the Curve From Time Zero to the Last Sampling Time (AUC0-tlast/Dose) of M5717 and Pyronaridine | 29.931 ± 0.455 | 65.494 ± 0.153 | 50.417 ± 0.391 | 11.033 ± 0.625 | 14.792 ± 0.366 | 7.639 ± 0.303 |
The dose normalized AUC from time zero extrapolated to infinity. Normalized using dose, using the formula AUC0-∞ /Dose.
| h*ng/mL/mg | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Dose Normalized Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-∞/Dose) of M5717 and Pyronaridine | 33.923 ± 0.238 | 66.615 ± 0.153 | 51.146 ± 0.384 | 12.216 ± 0.590 | 15.847 ± 0.347 | 8.194 ± 0.289 |
Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
| hours (h) | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Terminal Elimination Rate Constant (Lambda z) of M5717 and Pyronaridine | 0.009 ± 0.264 | 0.011 ± 0.152 | 0.008 ± 0.325 | 0.004 ± 0.599 | 0.003 ± 0.233 | 0.003 ± 0.314 |
The dose normalized maximum concentration. Normalized using the dose, and the formula Cmax /Dose.
| ng/mL/mg | Cohort A: M5717 330 mg | Cohort B0: M5717 500 mg | Cohort B0: M5717 660 mg | Cohort A and B0: Pyronaridine 360 mg | Cohort B0: Pyronaridine 540 mg | Cohort B0: Pyronaridine 720 mg |
|---|---|---|---|---|---|---|
| Cohort A and Cohort B0: Dose Normalized Maximum Concentration (Cmax/Dose) of M5717 and Pyronaridine | 0.816 ± 0.483 | 1.912 ± 0.173 | 1.502 ± 0.385 | 12.216 ± 0.590 | 15.847 ± 0.347 | 8.194 ± 0.289 |
Early treatment failure (ETF) was defined as meeting any of the following : 1. Danger signs or severe malaria 1, 2, or 3 days after treatment, in the presence of parasitemia2. Parasitemia 2 days after treatment higher than on day of treatment, irrespective of axillary temperature • Parasitemia 3 days after treatment with temperature ≥ 37.5°C 3. Parasitemia 3 days after treatment ≥ 25% of count on day of treatment. ETF rate will be estimated with 95% confidence intervals. Confidence intervals was derived by use of Wilson's score method.
| percentage of participants | Cohort A: M5717+Pyronaridine | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine |
|---|---|---|
| Cohort A and Cohort B0: Percentage of Participants With Early Treatment Failure (ETF) | 0.0 (0.0 to 24.3) | 0.0 (0.0 to 12.9) |
Late clinical failure (LCF) was defined as:1. Danger signs or severe malaria in the presence of parasitemia on any day between 4 and 28 days after treatment (i.e., between Days 5 and 29) in participants who did not previously meet any of the criteria of ETF. 2. Presence of parasitemia on any day between 4 and 28 days after treatment with temperature ≥ 37.5°C in participants who did not previously meet any of the criteria of ETF. LCF was estimated with 95% confidence intervals. Confidence intervals will be derived by use of Wilson's score method.
| percentage of participants | Cohort A: M5717+Pyronaridine | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine |
|---|---|---|
| Cohort A and Cohort B0: Percentage of Participants With Late Clinical Failure (LCF) | 0.0 (0.0 to 24.3) | 0.0 (0.0 to 12.9) |
Late parasitological failure (LPF) was defined as: Presence of parasitemia on any day between 7 and 28 days after treatment (i.e., between Days 8 and 29) with temperature \< 37.5°C in participants who did not previously meet any of the criteria of ETF or LCF. LPF was estimated with 95% confidence intervals. Confidence intervals will be derived by use of Wilson's score method.
| percentage of participants | Cohort A: M5717+Pyronaridine | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine |
|---|---|---|
| Cohort A and Cohort B0: Percentage of Participants With Late Parasitological Failure (LPF) | 0.0 (0.0 to 24.3) | 0.0 (0.0 to 12.9) |
PCR-adjusted ACPR 28 and 42 days after treatment defined as absence of parasitemia (thick smear/microscopy, after adjustment for parasitemia due to new infections as determined by genotyping using PCR techniques), irrespective of axillary temperature, in participants who did not previously meet any of the criteria of ETF, LCF, or LPF.
| percentage of participants | Cohort A: M5717+Pyronaridine |
|---|---|
| Day 28 | 91.7 (64.6 to 98.5) |
| Day 42 | 91.7 (64.6 to 98.5) |
Crude ACPR 28 and 42 days after first dose is defined as absence of parasitemia (parasite count = 0) from thick smear/microscopy, irrespective of axillary temperature, in participants who did not previously meet any of the criteria of ETF, LCF, or LPF.
| percentage of participants | Cohort A: M5717+Pyronaridine | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine |
|---|---|---|
| Day 28 | 91.7 (64.6 to 98.5) | 92.3 (75.9 to 97.9) |
| Day 42 | 91.7 (64.6 to 98.5) | 76.9 (57.9 to 89.0) |
Fever clearance time was defined as the time from first dosing to the first measurement of temperature \< 37.5°C for 2 consecutive temperature readings plus confirmed normal temperature 24 h after the first normal body temperature reading. This analysis was done on participants with fever.
| hours | Cohort A: M5717+Pyronaridine | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine |
|---|---|---|
| Cohort A and Cohort B0: Time to Fever Clearance as Estimated by Kaplan-Meier Method | 6.0 (6.0 to 6.0) | 6.2 (6.0 to 17.9) |
Parasite clearance time defined as time from dosing to the first negative (no parasites) film
| days | Cohort A: M5717+Pyronaridine | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine |
|---|---|---|
| Cohort A and Cohort B0: Parasite Clearance Time as Estimated by Kaplan-Meier Method | 4.0 (3.0 to 9.0) | 4.5 (2.0 to 10.0) |
An adverse event (AE) was defined as any untoward medical occurrence in a participant. TEAEs are defined as AEs which started at or after the administration of study intervention (study treatment) or which started prior to the first administration of study intervention but worsened after the dose intake, until the last scheduled assessment will be regarded as treatment-emergent, but before established rescue antimalarial treatment is administered, if required. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was considered to be "related" if a causal relationship between study treatment and the TEAE is at least reasonably possible.
| Participants | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine |
|---|---|
| TEAEs | 16 |
| Serious TEAEs | 0 |
| Related TEAEs | 0 |
Collected over Up to Day 43. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort A: M5717+Pyronaridine | 0/12 (0%) | 0/12 (0%) | 9/12 (75%) |
| Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine | 0/26 (0%) | 0/26 (0%) | 16/26 (61.5%) |
| Event | Cohort A: M5717+Pyronaridine | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine |
|---|---|---|
| HeadacheNervous system disorders | 5/12 | 1/26 |
| Blood alkaline phosphatase increasedInvestigations | 0/12 | 5/26 |
| Urinary tract infectionInfections and infestations | 2/12 | 1/26 |
| DizzinessNervous system disorders | 2/12 | 0/26 |
| MalariaInfections and infestations | 0/12 | 4/26 |
| AnaemiaBlood and lymphatic system disorders | 0/12 | 3/26 |
| Upper respiratory tract infectionInfections and infestations | 1/12 | 3/26 |
| Conjunctivitis viralInfections and infestations | 0/12 | 2/26 |
| Blood bilirubin increasedInvestigations | 0/12 | 2/26 |
| Age, Continuous(Years) | Cohort A: M5717+Pyronaridine | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine | Total |
|---|---|---|---|
| Mean | 23 ± 9.56 | 18 ± 9.03 | 20 ± 9.38 |
| Sex: Female, Male(Participants) | Cohort A: M5717+Pyronaridine | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine | Total |
|---|---|---|---|
| Female | 11 | 15 | 26 |
| Male | 1 | 11 | 12 |
| Race/Ethnicity, Customized(Participants) | Cohort A: M5717+Pyronaridine | Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine | Total |
|---|---|---|---|
| Ethnicity-Hispanic or Latino | 0 | 1 | 1 |
| Ethnicity-Not Hispanic or Latino | 0 | 25 | 25 |
| Ethnicity-Unknown or Not Reported | 12 | 0 | 12 |
| Race-Black or African American | 12 | 25 | 37 |
| Race-White | 0 | 1 | 1 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
Supporting information: Study protocol, Statistical analysis plan, Clinical study report, Analytic code
Time frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
Access criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
Data sharing details ↗ · bit.ly
This study is completed, as verified in Aug 2025. 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.
Studies of the drugs tested here: Cabamiquine · Pyronaridine
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany →