Pyronaridine Artesunate (3:1) in Children and Adults With Acute Plasmodium Vivax Malaria
NCT ID: NCT00440999
Last Updated: 2021-11-02
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
456 participants
INTERVENTIONAL
2007-03-31
2008-09-30
Brief Summary
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Detailed Description
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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
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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pyronaridine artesunate
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.
Pyronaridine artesunate
chloroquine
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.
Chloroquine
Interventions
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Pyronaridine artesunate
Chloroquine
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition.
3. 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).
4. 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.
5. Ability to swallow oral medication.
6. Ability and willingness to participate based on information given to patient or parent or guardian and access to health facility.
Exclusion Criteria
2. Presence of other clinical condition requiring hospitalization.
3. Presence of significant anaemia, as defined by Hb \<8 g/dL.
4. 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).
5. Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, chloroquine or artesunate or other artemisinins.
6. Known history of hypersensitivity, allergic or adverse reactions to chloroquine, primaquine and related agents.
7. Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab).
8. Known seropositive HIV antibody.
9. Have received any antimalarial treatment in the preceding 2 weeks, as determined by history and, whenever feasible, by screening test.
10. Have received antibacterial with known antimalarial activity in the preceding 2 weeks.
11. Have received any investigational drug within the past 4 weeks.
12. Liver function tests (AST/ALT levels) \>2.5 times the upper limit of normal range.
13. Known significant renal impairment as indicated by serum creatinine levels of \>1.4 mg/dL.
14. 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.
15. Previous participation in the present clinical trial with PA.
3 Years
60 Years
ALL
No
Sponsors
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Shin Poong Pharmaceuticals
INDUSTRY
Medicines for Malaria Venture
OTHER
Responsible Party
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Principal Investigators
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Isabelle Borghini Fuhrer, PhD
Role: STUDY_DIRECTOR
Medicines for Malaria Venture
Locations
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Pailin Referral Hospital
Pailin, Pailin, Cambodia
Wentlock District Hospital
Mangalore, , India
RSUD TC Hillers
Maumere, Nusa Tenggara Timur, Indonesia
MaeLamad District Hospital
Mae Ramat, Changwat Tak, Thailand
MaeSod General Hospital
Mae Sot, Changwat Tak, Thailand
Countries
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References
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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.
Ayyoub 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.
Duparc 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.
Other Identifiers
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SP-C-006-06
Identifier Type: -
Identifier Source: org_study_id