MalariaPhase 3NCT00440999
Pyronaridine Artesunate (3:1) in Children and Adults With Acute Plasmodium Vivax Malaria
A Phase 3 study testing Pyronaridine artesunate and Chloroquine in people with Malaria, run by Medicines for Malaria Venture at 5 sites in 4 countries.
Trial summary
The purpose of this study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) (180:60 mg) with that of standard chloroquine therapy in children and adults with acute, uncomplicated Plasmodium vivax malaria. 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 Chloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 456 participants
- Where
- 5 sitesin 4 countries
- Study dates
- Mar 2007to Sep 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. vivax mono-infection confirmed by:
- Fever, as defined by axillary/tympanic temperature ≥37.5°C or oral/rectal temperature ≥38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,
- Positive microscopy of P. vivax with parasite density ≥250/ mcL of blood (including at least 50% of asexual parasites).
- Written informed consent, in accordance with local practice, provided by patient and/or parent/guardian/spouse. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations.
- Ability to swallow oral medication.
- Ability and willingness to participate based on information given to patient or parent or guardian and access to health facility.
Who cannot join
- Presence of a mixed Plasmodium infection.
- Presence of other clinical condition requiring hospitalization.
- Presence of significant anaemia, as defined by Hb <8 g/dL.
- Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval ≥450 msec), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric or other abnormality (including recent head trauma).
- Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, chloroquine or artesunate or other artemisinins.
- Known history of hypersensitivity, allergic or adverse reactions to chloroquine, primaquine and related agents.
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- Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab).
- Known seropositive HIV antibody.
- Have received any antimalarial treatment in the preceding 2 weeks, as determined by history and, whenever feasible, by screening test.
- Have received antibacterial with known antimalarial activity in the preceding 2 weeks.
- Have received any investigational drug within the past 4 weeks.
- Liver function tests (AST/ALT levels) >2.5 times the upper limit of normal range.
- Known significant renal impairment as indicated by serum creatinine levels of >1.4 mg/dL.
- 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.
- Previous participation in the present clinical trial with PA.
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Thailand2 sites
MaeLamad District Hospital
Mae Ramat, Changwat Tak
MaeSod General Hospital
Mae Sot, Changwat Tak
About this study
Official title: A Phase III Comparative (Double-blind, Double-dummy) Randomised Multicentre Study to Assess the Safety & Efficacy of Oral Pyronaridine Artesunate (180:60 mg) Versus Chloroquine (155 mg) in Children & Adult Patients With Acute Vivax Malaria
The purpose of this study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) (180:60 mg) with that of standard chloroquine therapy in children and adults with acute, uncomplicated Plasmodium vivax malaria.
Read the detailed description
This is a multi-centre, randomised, double-blind, double-dummy, parallel-group, non-inferiority study comparing the efficacy and safety of the fixed combination of pyronaridine/artesunate (ie, PP/AS [PA]) (180:60 mg) with that of standard chloroquine therapy in children and adults with acute uncomplicated P. vivax malaria. The study population will include 456 patients, comprising male and female children (≥20 kg body weight) and adults recruited from study sites in South East Asia and India.
Patients will be randomised in a 1:1 ratio to receive either oral PA (180:60 mg tablets) plus chloroquine-placebo or oral chloroquine (155 mg tablets).plus PA-placebo, once a day for 3 consecutive days (Days 0, 1, and 2). For PA, posology was based on body weight ranges with subjects receiving 1 to 4 tablets depending on their body weight. The dose range covered by this regimen is 7.2:2.4 mg/kg to 13.8:4.6 mg/kg, which has been shown to be effective and safe in Phase I and II studies. The chloroquine daily dose is 10 mg/kg on Days 0 and 1 and 5 mg/kg on Day 2 for children, and 620 mg on Days 0 and 1 and 310 mg on Day 2 for adults.
Patients will be confined to the study facility for ≥4 days (Days 0,1,2 \& 3) and ideally 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 crude cure rate on Day 14, which is defined as the absence of P. vivax parasitaemia on Day 14. 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.
For patients who complete the study up to Day 28 and who have normal glucose-6-phosphate dehydrogenase (G-6-PD) activity, a 14-day course of primaquine (15 mg/day for adults and 0.3 mg/kg/day for children) will be administered starting on Day 28 to complete their radical cure. Subjects who are deficient in G-6-PD and who completed the study up to Day 28 will be treated per country policy.
- Conditions
- Malaria
- Being tested
- Pyronaridine artesunate, Chloroquine
- Keywords
- P vivax, malaria, artemisinin based combination therapy (ACT), antimalarial, 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
ChloroquineDrug
| Study group | Role | What they receive |
|---|---|---|
| pyronaridine artesunate | Experimental | The tablet strength is 180:60 mg oral PA plus chloroquine-placebo. Depending on their body weight, patients receive 1 to 4 tablets once a day, for 3 days. The actual dose-level range covered by this regimen is 7.2: 2.4 mg/kg to 13.8:4.6 mg/kg pyronaridine artesunate. Receives: Drug: Pyronaridine artesunate |
| chloroquine | Active comparator | The tablet strength is 155 mg oral chloroquine plus PA-placebo.
Patients receive:
For adults: 620 mg (i.e. 4 tablets) on Days 0 and 1 and 310 mg (i.e. 2 tablets) on Day 2. For children: 10 mg/kg on Days 0 and 1 and 5 mg/kg on Day 2. Receives: Drug: Chloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Crude Cure Rate on Day 14
Cure rate on Day 14 is defined as the absence of P. vivax parasitaemia on Day 14 irrespective of temperature (axillary, oral, tympanic, rectal) without previously meeting any of the criteria of treatment failure throughout the follow-up period.
Measured: Day 14
Secondary outcomes (6)
Crude Cure Rate on Days 21 and 28.
Cure on Day 21 and 28 is defined as the absence of P. vivax parasitaemia on Day 21 and 28 irrespective of temperature (axillary, oral, tympanic, rectal) without previously meeting any of the criteria of treatment failure throughout the follow-up period.
Measured: Day 21 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 to 42
Fever Clearance Time
Fever clearance time is defined as the time from first dosing to the first normal reading of temperature (<37.5°C for axillary/tympanic or <38°C for oral/rectal) for 2 consecutive normal temperature readings taken between 7 and 25 hours apart.
Measured: Days 0 to 42
Percentage of Subjects With Parasite Clearance on Days 1, 2, and 3
Percentage of subjects with parasite clearance on Day 1 (24 hours after first dose), Day 2 (48 hours after first dose), and Day 3 (72 hours after first dose).
Measured: Days 1, 2, and 3
Percentage of Subjects With Fever Clearance on Days 1, 2, and 3
Percentage of subjects with fever clearance on Day 1 (24 hours after first dose), Day 2 (48 hours after first dose), and Day 3 (72 hours after first dose).
Measured: Day 1, 2, and 3
Number of Participants With Adverse Events
Number of participants with adverse events, including 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 posted27 Feb 2007 (estimated)
- Study startMar 2007
- Primary completionApr 2008
- Study completionSep 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 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
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 456 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
- NCT00440999
- Sponsor's protocol ID
- SP-C-006-06
- Status last verified
- Oct 2021
- First submitted
- 26 Feb 2007
- Last updated
- 2 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Poravuth Y, Socheat D, Rueangweerayut R, Uthaisin C, Pyae Phyo A, Valecha N, Rao BH, Tjitra E, Purnama A, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L. Pyronaridine-artesunate versus chloroquine in patients with acute Plasmodium vivax malaria: a randomized, double-blind, non-inferiority trial. PLoS One. 2011 Jan 18;6(1):e14501. doi: 10.1371/journal.pone.0014501.
PubMed 21267072Ayyoub 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