Pyronaridine and Artesunate (3:1) in Children With Acute Uncomplicated Plasmodium Falciparum Malaria

NCT00331136 | Completed Phase 2 Results

• 1 other identifier: SP-C-003-05
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate three dose levels of a combination tablet and a fixed dose granule formulation of pyronaridine and artesunate (PA) for the treatment of acute uncomplicated falciparum malaria in children.

Conditions

Uncomplicated Plasmodium Falciparum Malaria

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28

  Clearance of asexual parasitaemia within 7 days of initiation of study medication without recrudescence within 28 days, without previously meeting any of the criteria for early treatment failure, late clinical failure, or late parasitological failure.

  Day 28

Secondary Outcomes (9)

• Parasite Clearance Time

  Day 3

• Treatment Success or Failure

  Day 28

• Fever Clearance Time

  Day 3

• Number of Patients With PCR-corrected ACPR on Day 14

  Day 14

• Number of Patients With Parasite Clearance at Day 1, 2 and 3

  Days 1, 2, 3

Study Arms (4)

Group A (Tablets)

EXPERIMENTAL

Pyronaridine artesunate 6:2 mg/kg. The tablet strength is 48:16 mg oral PA, with the number of tablets depending on body weight.

Drug: Pyronaridine-Artesunate

Group B (Tablets)

EXPERIMENTAL

Pyronaridine artesunate 9:3 mg/kg. The tablet strength is 72:24 mg oral PA, with the number of tablets depending on body weight.

Drug: Pyronaridine-Artesunate

Group C (Tablets)

EXPERIMENTAL

Pyronaridine artesunate 12:4 mg/kg. The tablet strength is 96:32 mg oral PA, with the number of tablets depending on body weight.

Drug: Pyronaridine-Artesunate

Group D (Granules)

EXPERIMENTAL

Pyronaridine artesunate 9:3 mg/kg. The sachet of granules strength is 60:20 mg PA, with the number of sachets depending on body weight, and is administered as a suspension with water.

Drug: Pyronaridine-Artesunate

Interventions

Pyronaridine-Artesunate DRUG

Once a day for 3 days

Also known as: Pyramax

Group A (Tablets); Group B (Tablets); Group C (Tablets); Group D (Granules)

Eligibility Criteria

• Age: 2 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female children, being between 2 and 14 years of age inclusive
• Weight between 10 and 40 kg inclusive
• Written informed consent, in accordance to local practice, provided by parent/guardian. If the parent/guardian is unable to write, witnessed consent is permitted according to local ethical considerations. Where possible, parent assent will be sought
• Absence of severe malnutrition (defined as mid upper arm circumference \<110mm)
• Presence of acute symptomatic uncomplicated P. falciparum malaria with a diagnosis confirmed by a positive blood smear with asexual forms of P. falciparum only (i.e. no mixed infection) plus measured temperature of ≥37.5°C (depending on method of measurement as below) or history of fever within the past 24 hours :
• the acceptable range is between 1,000 and 200,000 asexual parasite count/μl of blood and
• axillary/tympanic temperature of ≥37.5°C or oral/rectal temperature of ≥38.0°C
• Females of childbearing potential are not allowed to be pregnant or lactating and must be willing to use adequate measures of contraception during the study period
• Ability to comply with the study visit schedule and the study protocol for the duration of the study

You may not qualify if:

• Patients with signs and symptoms of severe/complicated malaria requiring parenteral antimalarial treatment according to the WHO Criteria 2000
• Mixed Plasmodium infection
• Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, acute QTc interval greater or equal to 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 head trauma)
• Presence of febrile conditions caused by diseases other than malaria
• Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or artesunate or other artemisinins
• Use of any other antimalarial treatment within 2 weeks prior to start of the study as confirmed by Lignin test and Saker Solomon urine test
• For females of childbearing potential, positive urine pregnancy test or lactating
• Use of an investigational drug within the past 8 weeks
• Known active Hep A immunoglobulin, Hep B surface antigen, or Hep C antibody
• Known seropositive HIV antibody
• Liver function tests (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] levels) \>3 times the upper limit of normal
• Known significant renal impairment as indicated by a serum creatinine ≥2 mg/dL
• Previous participation in this clinical study

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Shin Poong Pharmaceuticals: collaborator
• Institute of Tropical Medicine, University of Tuebingen: collaborator

Study Sites (1)

Medical Research Unit, Albert Schweitzer Hospital

Lambaréné, Gabon

Location

Related Publications (5)

• Ringwald P, Bickii J, Basco L. Randomised trial of pyronaridine versus chloroquine for acute uncomplicated falciparum malaria in Africa. Lancet. 1996 Jan 6;347(8993):24-8. doi: 10.1016/s0140-6736(96)91558-5.

  PMID: 8531545 BACKGROUND

• Ramharter M, Djimde AA, Borghini-Fuhrer I, Miller R, Shin J, Aspinall A, Richardson N, Wibberg M, Fleckenstein L, Arbe-Barnes S, Duparc S. Safety and efficacy of pyronaridine-artesunate paediatric granules in the treatment of uncomplicated malaria in children: insights from randomized clinical trials and a real-world study. Malar J. 2024 Feb 28;23(1):61. doi: 10.1186/s12936-024-04885-3.

  PMID: 38418982 DERIVED

• 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

• Ramharter M, Kurth F, Schreier AC, Nemeth J, Glasenapp Iv, Belard S, Schlie M, Kammer J, Koumba PK, Cisse B, Mordmuller B, Lell B, Issifou S, Oeuvray C, Fleckenstein L, Kremsner PG. Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon. J Infect Dis. 2008 Sep 15;198(6):911-9. doi: 10.1086/591096.

  PMID: 18694333 DERIVED

Related Links

• Shin Poong Pharmaceuticals

MeSH Terms

Conditions

Malaria

Interventions

pyronaridine tetraphosphate, artesunate drug combination

Condition Hierarchy (Ancestors)

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

Results Point of Contact

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

duparcs@mmv.org

+41 22 555 0300

Study Officials

• Michael Ramharter, MD

  Albert Schweitzer Hospital, Lambaréné, Gabon

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2006
• First Posted: May 29, 2006
• Study Start: June 1, 2006
• Primary Completion: December 1, 2006
• Study Completion: December 1, 2006
• Last Updated: May 5, 2022
• Results First Posted: November 22, 2021

Record last verified: 2022-05

Locations

GA (1)