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

Phase 2

Completed

• Conditions: Malaria, Falciparum
• Interventions: Drug: Pyronaridine-artesunate

• Registration Number: NCT02389439
• Lead Sponsor: University of Oxford

Brief Summary

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).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2015-01-29
• Study Start: 2015-03-01
• Study First Submitted QC: 2015-03-10
• Study First Posted: 2015-03-17
• Status Verified: 2015-04
• Primary Completion: 2015-12-01
• Study Completion: 2016-06-01
• Last Update Submitted: 2018-09-18
• Last Update Posted: 2018-09-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 123

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pyronaridine-artesunate	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

Primary Outcome Measures

Name	Time	Method
result of PCR	42 day

Secondary Outcome Measures

Name	Time	Method
eosinophil count	at day 0, 3, 7 and day 28
fever clearance time	24 hours	the time taken for tympanic temperature to fall below 37.5˚C and remain there for at least 24 hours
PCR uncorrected ACPR	at 28 days or 42 days	PCR uncorrected ACPR at 28 days or 42 days for P. falciparum, P. falciparum and mixed infections in Pailin
gametocyte clearance times	at day 0, 3, 7 and day28
hepatic biological values	at day 0, 3,7 and day 28	the hepatic biological values will be measured which are AST,ALT,albumin and total bilirubin
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
PCR corrected ACPR	at 28 days and 42 days	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
Number of patient with reinfection and recrudescences	over 42 days
Gametocyte carriage rates	at day 0, 3, 7 day 28

Trial Locations

Locations (3)

Promoy Health Centre (Pursat); 🇰🇭 Pursat), Cambodia

Tasanh Health Centre, Battambang; 🇰🇭 Battambang, Cambodia

Referral hospital (Pailin); 🇰🇭 Pailin, Cambodia