Efficacy and Safety of Pyronaridine-artesunate for the Treatment in Uncomplicated Falciparum Malaria

Monitoring and Evaluation of the Therapeutic Efficacy and Safety of Pyronaridine-artesunate for the Treatment of Uncomplicated Falciparum Malaria in Western Cambodia, an Area of Artemisinin-resistant Falciparum Malaria

This study is a prospective, single arm, open-labelled clinical trial. The total number subjects will be 145 patients to receive Pyronaridine-artesunate once daily for 3 days. Dosing will be according to the body weight.

All patients will have a blood smear examined daily during the first week by microscopy until parasite clearance (2 consecutive negative slides on two consecutive days; both asexual and sexual stages). A negative blood slide will be defined as parasite count negative per 1000 WBC in two consecutive days. The sample on day 3 will be taken as close as possible to 72h after the initial blood smear.

Participant will follow up for 42 days to assess the drug efficacy and safety (Day 7, 14, 21, 28, 35 and 42).

Study Overview

• Status: Completed
• Conditions: Malaria, Falciparum
• Intervention / Treatment: Drug: Pyronaridine-artesunate

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 2

Contacts and Locations

Study Locations

• Cambodia
  • Battambang, Cambodia
    • Tasanh Health Centre, Battambang
  • Pailin, Cambodia
    • Referral hospital (Pailin)
  • Pursat), Cambodia
    • Promoy Health Centre (Pursat)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults and children ≥ 20 kg
• Symptomatic of malaria infection, i.e. history of fever within 24 hours and/or presence of fever >37.5°c.
• Microscopic confirmation of asexual stages of P. falciparum (P. falciparum and mixed infection in Pailin only)
• Capability of taking an oral medication
• Written informed consent given to participate in the trial
• Willingness and ability to adhere to follow-up visit schedule

Exclusion Criteria:

• Pregnancy or lactation (urine test for β HCG to be performed on any woman of child bearing age, that is 18 to 45 y/o)
• Female aged 12-18y
• Parasitemia > 150 000/µL).

• Signs or symptoms indicative of severe malaria:

  • Impaired consciousness (Blantyre Coma Score <5)
  • Severe anaemia (Hct<15%)
  • Bleeding disorder -evidenced by epistaxis, bleeding gums, frank haematuria, bleeding from venepuncture sites
  • Respiratory distress
  • Severe jaundice
• Known hypersensitivity to artemisinins - defined as history of erythroderma/other severe cutaneous reaction, angioedema or to pyronaridine
• History of splenectomy

• Known history or evidence of clinically significant disorders, such as:

  • Known active Hepatitis A, e.g. by detection of anti HAV-IgM.
  • Known hepatitis B surface antigen (HBsAg) carrier.
  • Known hepatitis C antibody (HCV Ab).
  • Liver function tests (AST/ALT levels) more than 2.5 times the upper limit of normal range.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pyronaridine-artesunate; Pyronaridine-artesunate (Pyramax®, Shin Poong Pharmaceuticals). One tablet contains 60mg artesunate+ 180mg pyronaridine. Dosing will be according to body weight. It will be taken orally with water, once daily for 3 days. Each dose will be administered under the supervision. A dose will be repeated in full if vomiting occurs within 30 minutes of administration of the first day of administration only. 20 - < 24 kg = 1 tab 24 - < 45 kg = 2 tabs 45 - < 65 kg = 3 tabs 65 and above = 4 tabs

Drug: Pyronaridine-artesunate; Other Names: Pyramax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
result of PCR	42 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hepatic biological values	the hepatic biological values will be measured which are AST,ALT,albumin and total bilirubin	at day 0, 3,7 and day 28
eosinophil count		at day 0, 3, 7 and day 28
K13 and pfmdr1 of P falciparum resistance		at day 0, 3, 7 and day 28
numbers of patients with a positive malaria slide 72 hours after treatment initiation		72 hours
fever clearance time	the time taken for tympanic temperature to fall below 37.5˚C and remain there for at least 24 hours	24 hours
Number of patient with reinfection and recrudescences		over 42 days
PCR uncorrected ACPR	PCR uncorrected ACPR at 28 days or 42 days for P. falciparum, P. falciparum and mixed infections in Pailin	at 28 days or 42 days
PCR corrected ACPR	PCR corrected ACPR at 28 days or for P. falciparum, P. vivax and mixed infections and at 42 days for P. falciparum and mixed infections	at 28 days and 42 days
Gametocyte carriage rates		at day 0, 3, 7 day 28
gametocyte clearance times		at day 0, 3, 7 and day28

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: NCHADS - Ministry of Health of Cambodia

Publications and helpful links

General Publications

• Leang R, Canavati SE, Khim N, Vestergaard LS, Borghini Fuhrer I, Kim S, Denis MB, Heng P, Tol B, Huy R, Duparc S, Dondorp AM, Menard D, Ringwald P. Efficacy and Safety of Pyronaridine-Artesunate for Treatment of Uncomplicated Plasmodium falciparum Malaria in Western Cambodia. Antimicrob Agents Chemother. 2016 Jun 20;60(7):3884-90. doi: 10.1128/AAC.00039-16. Print 2016 Jul.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: January 29, 2015
• First Submitted That Met QC Criteria: March 10, 2015
• First Posted (Estimate): March 17, 2015

Study Record Updates

• Last Update Posted (Actual): September 20, 2018
• Last Update Submitted That Met QC Criteria: September 18, 2018
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artesunate; Pyronaridine
• Other Study ID Numbers: Cambodia1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No