Pyronaridine Artesunate (3:1) in Children and Adults With Acute Plasmodium Vivax Malaria

NCT00440999 | Completed Phase 3 Results DMC

• 1 other identifier: SP-C-006-06
• Study Type: interventional
• Target: 456
• Locations: 4 countries
• Sites: 5

Brief 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.

Conditions

Malaria

Keywords

P vivax; malaria; artemisinin based combination therapy (ACT); antimalarial; pyronaridine artesunate (Pyramax)

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 14

Secondary Outcomes (6)

• Crude Cure Rate on Days 21 and 28.

  Day 21 and 28

• Parasite Clearance Time

  Days 0 to 42

• Fever Clearance Time

  Days 0 to 42

• Percentage of Subjects With Parasite Clearance on Days 1, 2, and 3

  Days 1, 2, and 3

• Percentage of Subjects With Fever Clearance on Days 1, 2, and 3

  Day 1, 2, and 3

Other Outcomes (2)

• Percentage of Subjects With PCR-corrected Cure Rate on Days 14, 21, and 28

  Day 14, 21, and 28

• Percentage of Subjects With Crude and PCR-corrected Cure Rate on Day 42

  Day 42

Study Arms (2)

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.

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.

Drug: Chloroquine

Interventions

Pyronaridine artesunate DRUG

Also known as: Pyramax

pyronaridine artesunate

Chloroquine DRUG

chloroquine

Eligibility Criteria

• Age: 3 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Shin Poong Pharmaceuticals: collaborator

Study Sites (5)

Pailin Referral Hospital

Pailin, Pailin, Cambodia

Location

Wentlock District Hospital

Mangalore, India

Location

RSUD TC Hillers

Maumere, Nusa Tenggara Timur, 86113, Indonesia

Location

MaeLamad District Hospital

Mae Ramat, Changwat Tak, Thailand

Location

MaeSod General Hospital

Mae Sot, Changwat Tak, Thailand

Location

Related Publications (3)

• 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.

  PMID: 21267072 RESULT

• 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.

  PMID: 26666916 DERIVED

• 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.

  PMID: 23433102 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

pyronaridine tetraphosphate, artesunate drug combination; Chloroquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Stephan Duparc, MD
• Organization: Medicines for Malaria Venture

duparcs@mmv.org

+41 22 555 0300

Study Officials

• Isabelle Borghini Fuhrer, PhD

  Medicines for Malaria Venture

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2007
• First Posted: February 27, 2007
• Study Start: March 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: September 1, 2008
• Last Updated: November 2, 2021
• Results First Posted: September 20, 2021

Record last verified: 2021-10

Locations

CA (1); IN (1); TH (2); ID (1)