MalariaPhase 3NCT00422084
Pyronaridine Artesunate (3:1) Versus Coartem® in P Falciparum Malaria Patients
A Phase 3 study testing Pyronaridine artesunate and Coartem® (artemether lumefantrine) in people with Malaria, run by Medicines for Malaria Venture at 10 sites in 9 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 3 to 60 years
- Conditions the study is for
- Malaria
- What is being tested?
- Pyronaridine artesunate and Coartem® (artemether lumefantrine)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,272 participants
- Where
- 10 sitesin 9 countries
- Study dates
- Jan 2007to May 2008
- Phase
- Phase 3
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 age 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, in accordance with local practice, 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.
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- Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, lumefantrine or artesunate or other artemisinins.
- Patients with known disturbances of electrolytes balance, e.g., hypokalaemia or hypomagnesaemia.
- Use of any other antimalarial agent within 2 weeks prior to start of the study as evidenced by a 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.
- Patients taking any drug which is metabolised by the cytochrome enzyme CYP2D6 (flecainide, metoprol, imipramine, amitriptyline, clomipramine).
- Received an investigational drug within the past 4 weeks.
- Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen. (HBsAg) or Hepatitis C antibody (HCV Ab).
- Known seropositive HIV antibody.
- Liver function tests [ASAT/ALAT levels] >2.5 times the upper limit of normal range.
- Known significant renal impairment as indicated by serum creatinine >1.4 mg/dL.
Trial locations and contacts
10 sites in 9 countries.
10 sites in 9 countries
Indonesia2 sites
Jayapura General Hospital (RSUD) DOK II
Jayapura, Special Region of Papua
RSUD TC Hillers
Maumere, East Nusa Tenggara, 86113
Democratic Republic of the Congo1 site
Ecole de Santé Publique, Faculté de Médecine, Université de Kinshasa
Kinshasa
Mali1 site
Malaria Research and Training Center, Faculté de Médecine, de Pharmacie et d'Ondonto-stomatologie
Bamako
Senegal1 site
Service de Parasitologie, Faculté de Médecine, Université Cheikh Anta Diop
Dakar, Dakar Fann
About this study
Official title: A Phase III Comparative (Double-blind, Double-dummy) Randomised, Multi-centre Study to Assess the Efficacy of Pyronaridine Artesunate (180:60mg) Versus Coartem® (Artemether Lumefantrine) in Children & Adult Patients With Falciparum Malaria
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.
Read the detailed description
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.
- Conditions
- Malaria
- Being tested
- Pyronaridine artesunate, Coartem® (artemether lumefantrine)
- Keywords
- malaria, antimalarial, artemisinin based combination therapy (ACT), P. falciparum, pyronaridine artesunate (Pyramax)
- Medical subject headings
- 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
Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)
Coartem® (artemether lumefantrine)Drug
Also called Coartem
AL (20:120mg tablets) twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)
| Study group | Role | What they receive |
|---|---|---|
| PA group | Experimental | Pyronaridine artesunate (PA) Receives: Drug: Pyronaridine artesunate |
| AL group | Active comparator | Arthemether lumefantrine (AL) Receives: Drug: Coartem® (artemether lumefantrine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 28
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
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 posted15 Jan 2007 (estimated)
- Study startJan 2007
- Primary completionApr 2008
- Study completionMay 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 (4)Papers the sponsor has linked to this study.
- Other trials for 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1,272 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
- Claude Oeuvray, PhD, Study director, Medicines for Malaria Venture
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00422084
- Sponsor's protocol ID
- SP-C-005-06
- Status last verified
- Oct 2021
- First submitted
- 12 Jan 2007
- Last updated
- 2 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Tshefu AK, Gaye O, Kayentao K, Thompson R, Bhatt KM, Sesay SS, Bustos DG, Tjitra E, Bedu-Addo G, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L; Pyronaridine-artesunate Study Team. Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial. Lancet. 2010 Apr 24;375(9724):1457-67. doi: 10.1016/S0140-6736(10)60322-4.
PubMed 20417857Pryce J, Taylor M, Fox T, Hine P. Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria. Cochrane Database Syst Rev. 2022 Jun 21;6(6):CD006404. doi: 10.1002/14651858.CD006404.pub4.
PubMed 35726133Ayyoub 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