Phase II Dose-ranging Study of Pyronaridine/Artesunate in Adults Patients With Plasmodium Falciparum Malaria

NCT01594931 | Completed Phase 2 Results DMC

• 1 other identifier: SP-C-002-05
• Study Type: interventional
• Target: 477
• Locations: 5 countries
• Sites: 5

Brief Summary

The primary trial objective is to determine the clinically effective dose of orally administered pyronaridine/artesunate (Pyramax®, PA) with a 3:1 ratio to treat adults with acute, symptomatic, uncomplicated P. falciparum malaria in South East Asia and Africa. Secondary trial objectives are to determine the safety of once-daily dosing for 3 days of PA and to explore possible ethnic differences in safety or efficacy.

Conditions

Plasmodium Falciparum Malaria

Keywords

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

Outcome Measures

Primary Outcomes (1)

• PCR-Corrected ACPR at 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

  Day 28

Secondary Outcomes (6)

• PCR-Corrected ACPR at Day 14

  Day 14

• Parasite Clearance Time

  Thick blood slides were examined every 8 hours until at least 72 hours or until a negative smear was recorded

• Fever Clearance Time

  Every 8 hours for at least 72 hours after the first dose

• Parasite Clearance

  Days 1, 2, and 3

• Fever Clearance

  Days 1, 2 and 3

Study Arms (3)

pyronaridine/artesunate (6:2 mg/kg)

EXPERIMENTAL

pyronaridine tetraphosphate 6 mg/kg and artesunate 2 mg/kg

Drug: pyronaridine/artesunate

pyronaridine/artesunate (9:3 mg/kg)

EXPERIMENTAL

pyronaridine tetraphosphate 9 mg/kg and artesunate 3 mg/kg

Drug: pyronaridine/artesunate

pyronaridine/artesunate (12:4 mg/kg)

EXPERIMENTAL

pyronaridine tetraphsophate 12 mg/kg and artesunate 4 mg/kg

Drug: pyronaridine/artesunate

Interventions

pyronaridine/artesunate DRUG

Tablets of fixed dose combination of pyronaridine and artesunate at a ratio of 3:1. The tablets were taken daily for 3 days.

Also known as: Pyramax

pyronaridine/artesunate (12:4 mg/kg); pyronaridine/artesunate (6:2 mg/kg); pyronaridine/artesunate (9:3 mg/kg)

Eligibility Criteria

• Age: 15 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 15 and 60 years of age inclusive
• 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
• Absence of severe malnutrition (defined as the weight-for-height being below -3 standard deviations or \<70% of the median of the NCHS/WHO normalized reference values)
• Weight of between 35 kg and 75 kg inclusive
• 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 history of fever within the previous 24 hours or a measured temperature of ≥37.5°C (depending on method of measurement):
• the acceptable range is between 1,000 and 100,000 asexual parasite count/μl of blood and
• axillary/tympanic temperature of ≥ 37.5°C or oral/rectal temperature of ≥ 38.0°C
• Ability to swallow oral medication
• Ability to comply with study visit schedule: patients will be hospitalised for at least 4 days and will be required to remain in the vicinity of the trial site for a minimum of 7 days or until clearance of fever and parasite for at least 24 hours, whichever is the later. The patient is to return to the study site or to make themselves available for all scheduled follow up visits, until discharge at Day 42.
• Females must not be pregnant or lactating and be willing to take measures to not become pregnant during the study period
• Willingness and ability to comply with 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 treatment according to the World Health Organization Criteria 2000
• Mixed Plasmodium infection
• Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric or other clinically important 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
• Evidence of use of any other antimalarial agent within 2 weeks prior to the start of the study confirmed by a negative urine test or using Eggelte dipsticks
• Positive urine pregnancy test or lactating
• 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 upper limit of normal values
• Known significant renal impairment as indicated by a serum creatinine of ≥ 1.4 mg/dl
• Previous participation in this clinical trial

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Shin Poong Pharmaceutical Co. Ltd.: collaborator

Study Sites (6)

Pailin General Hospital

Pailin, Cambodia

Location

Bethesday Hospital

Tomohon, North Sulawesi, Indonesia

Location

Centre de santé du roi Baudoin

Guédiawaye, Senegal

Location

Faculty of Tropical Medicine, Mahidol University

Bangkok, Thailand

Location

Farafenni Field Station, c/o MRC Laboratories

Farafenni, The Gambia

Location

MSF Epicentre

Mbarara, Uganda

Location

Related Publications (1)

• 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, Falciparum; 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, Chief Medical Officer
• Organization: Medicines for Malaria Venture (MMV)

duparcs@mmv.org

+41 22 555 0300

Study Officials

• Sornchai Looareesuwan, MD

  Hospital of Tropical Diseases, Mahidol University, Bangkok, Thailand

  PRINCIPAL INVESTIGATOR

• Duong Socheat, MD

  Nat. Centre for Parasitol., Entomol. and Malaria Control, Phnom Penh, Cambodia

  PRINCIPAL INVESTIGATOR

• Emiliana Tjitra, PhD

  Bethesda Hospital, Tomohon, North Sulawasi, Indonesia

  PRINCIPAL INVESTIGATOR

• Kalifa Bojang, MD

  MRC Laboratories, Faraffeni, The Gambia

  PRINCIPAL INVESTIGATOR

• Patrice Piola, MD

  Epicentre, Mbarara, Uganda

  PRINCIPAL INVESTIGATOR

• Oumar Gaye, MD

  Centre de santé Roi Baudouin, Guediawaye, Senegal

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2012
• First Posted: May 9, 2012
• Study Start: July 1, 2005
• Primary Completion: March 1, 2006
• Study Completion: April 1, 2006
• Last Updated: November 2, 2021
• Results First Posted: September 17, 2021

Record last verified: 2021-10

Locations

UG (1); CA (1); TH (1); ID (1); SE (1)