Falciparum MalariaPhase 3NCT00403260
Pyronaridine - Artesunate (3:1) Versus Mefloquine Plus Artesunate in Plasmodium Falciparum Malaria Patients
A Phase 3 study testing Pyronaridine - artesunate and Mefloquine plus artesunate in people with Falciparum Malaria, run by Medicines for Malaria Venture at 9 sites in 7 countries.
Trial summary
The primary objective of this phase III clinical study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) with that of the combination of mefloquine plus artesunate (MQ + AS) in children and adults with uncomplicated P falciparum malaria in South East Asia, India… Read more about this study
- Who is it for?
- Ages 3 to 60 years
- Conditions the study is for
- Falciparum Malaria
- What is being tested?
- Pyronaridine - artesunate and Mefloquine plus artesunate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,271 participants
- Where
- 9 sitesin 7 countries
- Study dates
- Jan 2007to Dec 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male or female patients between the ages of 3 and 60 years, inclusive.
- Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition.
- Presence of acute uncomplicated P. falciparum mono-infection confirmed by:
- Fever, as defined by axillary/tympanic temperature ≥37.5°C or oral/rectal temperature ≥38°C, or documented history of fever in the previous 24 hours and,
- Positive microscopy of P. falciparum with parasite density between 1,000 and 100,000 asexual parasite count/µl of blood
- Written informed consent provided by patient and/or parent/guardian/spouse.
- Ability to swallow oral medication.
Who cannot join
- Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization Criteria 2000.
- Mixed Plasmodium infection.
- Severe vomiting or severe diarrhoea.
- Known history or evidence of clinically significant disorders.
- Presence of significant anaemia, as defined by Hb <8 g/dL.
- Presence of febrile conditions caused by diseases other than malaria.
Show all 14Show fewer
- Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, mefloquine or artesunate or other artemisinins.
- Use of any other antimalarial agent within 2 weeks prior to start of the study as evidenced by positive urine test.
- Female patients of child-bearing potential must be neither pregnant (as demonstrated by a negative pregnancy test) nor lactating, and must be willing to take measures to not become pregnant during the study period.
- Presence of significant renal or hepatic impairment.
- Receipt of an investigational drug within the past 4 weeks.
- Known active Hepatitis A IgM, Hepatitis B surface antigen or Hepatitis C antibody.
- Known seropositive HIV antibody.
- Previous participation in any clinical study with PA.
Trial locations and contacts
9 sites in 7 countries.
9 sites in 7 countries
Thailand2 sites
MaeLamad District Hospital
Mae Ramat, Changwat Tak
MaeSod General Hospital
Mae Sot, Changwat Tak
Burkina Faso1 site
RAOTAP2/Centre Muraz
Bobo-Dioulasso, Houet Province, 01 BP390
Tanzania1 site
Bagamoyo Research and Training Centre of Ifakara Health Institute
Bagamoyo
About this study
Official title: A Phase III Comparative, Open-label, Randomised, Multi-centre Study to Assess the Efficacy of Pyronaridine Artesunate (180:60mg) Versus Mefloquine (250mg) Plus Artesunate (100mg) in Children & Adult Patients With Acute Falciparum Malaria
The primary objective of this phase III clinical study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) with that of the combination of mefloquine plus artesunate (MQ + AS) in children and adults with uncomplicated P falciparum malaria in South East Asia, India and Africa.
Read the detailed description
This is a multi-centre, comparative, randomised, open-label, parallel-group, non-inferiority study comparing the efficacy and safety of a fixed combination of PA to a loose combination of MQ + AS for patients with acute, symptomatic, uncomplicated P. falciparum malaria. The study population will include 1271 patients, comprising male and female children (≥20 kg body weight) and adults, recruited from study sites in South East Asia, India and Africa. Patients will be randomised in a 2:1 ratio to receive either oral PA (180:60mg tablets) or MQ (250mg tablets) plus AS (100mg tablets) once a day for 3 consecutive days (Days 0, 1, and 2). The study drug will be administered by a Third-Party Investigator unblinded to the study treatment, while the Investigator remains blinded.
Patients will be confined to the 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.
The primary efficacy end point for the study is the proportion of subjects with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28 (defined as the absence of parasitaemia without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure). 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.
- Conditions
- Falciparum Malaria
- Being tested
- Pyronaridine - artesunate, Mefloquine plus artesunate
- Keywords
- malaria, antimalarial, P falciparum, pyronaridine, artesunate, artemisinin based combination therapy (ACT), pyronaridine artesunate (Pyramax)
- Medical subject headings
- Malaria, Falciparum, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyronaridine - artesunateDrug
Also called Pyramax
once a day for 3 days
Mefloquine plus artesunateDrug
once a day for 3 days
| Study group | Role | What they receive |
|---|---|---|
| Pyronaridine - artesunate | Experimental | Oral pyronaridine artesunate (180:60mg tablets) once a day for 3 consecutive days (Day 0, 1, and 2). Posology based on body weight ranges. Receives: Drug: Pyronaridine - artesunate |
| Mefloquine plus artesunate | Active comparator | Mefloquine (250mg tablets) plus artesunate (100mg tablets) once a day for 3 consecutive days (Day 0, 1, and 2). Posology based on body weight ranges. Receives: Drug: Mefloquine plus artesunate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Subjects With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) 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.
Measured: Day 28
Secondary outcomes (7)
PCR-corrected 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
Measured: Day 14
Crude ACPR on Days 14 and 28
Percentage of subjects with adequate clinical and parasitological response (ACPR) on Days 14 and 28, without correction by PCR, defined as absence of parasitaemia on Days 14 and 28 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure
Measured: Days 14 and 28
Parasite Clearance Time
Parasite clearance time was defined as the time from first dosing to 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.
Measured: Thick blood films were examined every 8 hours until ≥72 hours or until 2 consecutive negative readings occurred 7 to 25 hours apart, and on Days 3, 7, 14, 21, 28, 35, and 42 (or any other day if the subject returned).
Fever Clearance Time
Fever clearance time was defined as the time from first dosing to first normal reading of temperature (<37.5°C taken axillary or tympanic; <38°C taken oral or rectal) for 2 consecutive normal temperature readings taken between 7 and 25 hours apart.
Measured: Every 8 hours over ≥72 hours following first study drug administration or temperature normalisation for ≥2 readings between 7 and 25 hours apart, then at each visit.
Parasite Clearance at Day 1, 2 and 3
Parasite clearance time was 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.
Measured: Days 1, 2 and 3
Fever Clearance at Day 1, 2 and 3
Fever clearance time was defined as the time for at least 2 consecutive normal body temperature measurements (<37.5°C axillary/tympanic or <38.0°C oral/rectal) to be obtained within an interval of 7 to 25 hours post-dosing.
Measured: Days 1, 2 and 3
Adverse Events and Clinically Significant Laboratory Results
Cases and severity of adverse events and of clinically significant laboratory results, ECG, vital signs or physical examination abnormalities
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2006 (estimated)
- Study startJan 2007
- Primary completionOct 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Falciparum MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,271 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medicines for Malaria Venture
- Sponsor type
- University, hospital or other
- Collaborators
- Shin Poong Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Isabelle Borghini-Fuhrer, PhD, Study director, Medicines for Malaria Venture
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00403260
- Sponsor's protocol ID
- SP-C-004-06
- Status last verified
- Oct 2021
- First submitted
- 22 Nov 2006
- Last updated
- 2 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Rueangweerayut R, Phyo AP, Uthaisin C, Poravuth Y, Binh TQ, Tinto H, Penali LK, Valecha N, Tien NT, Abdulla S, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L; Pyronaridine-Artesunate Study Team. Pyronaridine-artesunate versus mefloquine plus artesunate for malaria. N Engl J Med. 2012 Apr 5;366(14):1298-309. doi: 10.1056/NEJMoa1007125.
PubMed 22475593Ayyoub A, Methaneethorn J, Ramharter M, Djimde AA, Tekete M, Duparc S, Borghini-Fuhrer I, Shin JS, Fleckenstein L. Population Pharmacokinetics of Pyronaridine in Pediatric Malaria Patients. Antimicrob Agents Chemother. 2015 Dec 14;60(3):1450-8. doi: 10.1128/AAC.02004-15.
PubMed 26666916Duparc S, Borghini-Fuhrer I, Craft CJ, Arbe-Barnes S, Miller RM, Shin CS, Fleckenstein L. Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials. Malar J. 2013 Feb 21;12:70. doi: 10.1186/1475-2875-12-70.
PubMed 23433102
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Comparative, Open-label, Randomised, Multi-centre Study to Assess the Efficacy of Pyronaridine Artesunate (180:60mg) Versus Mefloquine (250mg) Plus Artesunate (100mg) in Children & Adult Patients With Acute Falciparum Malaria
- ClinicalTrials.gov ID
- NCT00403260
- Acronym / sponsor ID
- SP-C-004-06
- Conditions
- Falciparum Malaria
- Keywords
- malaria, antimalarial, P falciparum, pyronaridine, artesunate, artemisinin based combination therapy (ACT), pyronaridine artesunate (Pyramax)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,271 participants (actual)
- Lead sponsor
- Medicines for Malaria VentureUniversity, hospital or other
- Collaborators
- Shin Poong Pharmaceuticals
- Study start
- Jan 2007 (actual)
- Primary completion
- Oct 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 23 Nov 2006 (estimated)
- Results
- Posted 17 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this phase III clinical study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) with that of the combination of mefloquine plus artesunate (MQ + AS) in children and adults with uncomplicated P falciparum malaria in South East Asia, India and Africa.
Detailed description
This is a multi-centre, comparative, randomised, open-label, parallel-group, non-inferiority study comparing the efficacy and safety of a fixed combination of PA to a loose combination of MQ + AS for patients with acute, symptomatic, uncomplicated P. falciparum malaria. The study population will include 1271 patients, comprising male and female children (≥20 kg body weight) and adults, recruited from study sites in South East Asia, India and Africa. Patients will be randomised in a 2:1 ratio to receive either oral PA (180:60mg tablets) or MQ (250mg tablets) plus AS (100mg tablets) once a day for 3 consecutive days (Days 0, 1, and 2). The study drug will be administered by a Third-Party Investigator unblinded to the study treatment, while the Investigator remains blinded.
Patients will be confined to the 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.
The primary efficacy end point for the study is the proportion of subjects with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28 (defined as the absence of parasitaemia without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure). 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pyronaridine - artesunate | Experimental | Drug: Pyronaridine - artesunateOral pyronaridine artesunate (180:60mg tablets) once a day for 3 consecutive days (Day 0, 1, and 2). Posology based on body weight ranges. |
| Mefloquine plus artesunate | Active comparator | Drug: Mefloquine plus artesunateMefloquine (250mg tablets) plus artesunate (100mg tablets) once a day for 3 consecutive days (Day 0, 1, and 2). Posology based on body weight ranges. |
Who may qualify
- Ages
- 3 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Male or female patients between the ages of 3 and 60 years, inclusive.
- Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition.
- Presence of acute uncomplicated P. falciparum mono-infection confirmed by:
- Written informed consent provided by patient and/or parent/guardian/spouse.
- Ability to swallow oral medication.
Key exclusion criteria (14 listed)
- Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization Criteria 2000.
- Mixed Plasmodium infection.
- Severe vomiting or severe diarrhoea.
- Known history or evidence of clinically significant disorders.
- Presence of significant anaemia, as defined by Hb <8 g/dL.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pyronaridine - artesunateAlso: Pyramaxonce a day for 3 days | Drug | Pyronaridine - artesunate |
| Mefloquine plus artesunateonce a day for 3 days | Drug | Mefloquine plus artesunate |
Primary outcome
Percentage of Subjects With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28
Time frame: 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.
7 secondary outcomes
PCR-corrected ACPR on Day 14
Time frame: Day 14
Crude ACPR on Days 14 and 28
Time frame: Days 14 and 28
Parasite Clearance Time
Time frame: Thick blood films were examined every 8 hours until ≥72 hours or until 2 consecutive negative readings occurred 7 to 25 hours apart, and on Days 3, 7, 14, 21, 28, 35, and 42 (or any other day if the subject returned).
Fever Clearance Time
Time frame: Every 8 hours over ≥72 hours following first study drug administration or temperature normalisation for ≥2 readings between 7 and 25 hours apart, then at each visit.
Parasite Clearance at Day 1, 2 and 3
Time frame: Days 1, 2 and 3
Fever Clearance at Day 1, 2 and 3
Time frame: Days 1, 2 and 3
Adverse Events and Clinically Significant Laboratory Results
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22475593Rueangweerayut R, Phyo AP, Uthaisin C, Poravuth Y, Binh TQ, Tinto H, Penali LK, Valecha N, Tien NT, Abdulla S, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L; Pyronaridine-Artesunate Study Team. Pyronaridine-artesunate versus mefloquine plus artesunate for malaria. N Engl J Med. 2012 Apr 5;366(14):1298-309. doi: 10.1056/NEJMoa1007125.
- Derived from this study: PubMed 26666916Ayyoub A, Methaneethorn J, Ramharter M, Djimde AA, Tekete M, Duparc S, Borghini-Fuhrer I, Shin JS, Fleckenstein L. Population Pharmacokinetics of Pyronaridine in Pediatric Malaria Patients. Antimicrob Agents Chemother. 2015 Dec 14;60(3):1450-8. doi: 10.1128/AAC.02004-15.
- Derived from this study: PubMed 23433102Duparc S, Borghini-Fuhrer I, Craft CJ, Arbe-Barnes S, Miller RM, Shin CS, Fleckenstein L. Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials. Malar J. 2013 Feb 21;12:70. doi: 10.1186/1475-2875-12-70.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Isabelle Borghini-Fuhrer, PhD study director
Medicines for Malaria Venture
9 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pyronaridine - artesunate and Mefloquine plus artesunate in people with Falciparum Malaria, run by Medicines for Malaria Venture at 9 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Thailand, Vietnam, Burkina Faso, Cambodia, Côte d’Ivoire and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Subjects With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28 (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00403260, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2021.