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

Primary Purpose

Malaria, Falciparum

Status
Completed
Phase
Phase 2
Locations
Cambodia
Study Type
Interventional
Intervention
Pyronaridine-artesunate
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malaria, Falciparum

Eligibility Criteria

7 Years - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pyronaridine-artesunate

Arm Description

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

Outcomes

Primary Outcome Measures

result of PCR

Secondary Outcome Measures

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

Full Information

First Posted
January 29, 2015
Last Updated
September 18, 2018
Sponsor
University of Oxford
Collaborators
NCHADS - Ministry of Health of Cambodia
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1. Study Identification

Unique Protocol Identification Number
NCT02389439
Brief Title
Efficacy and Safety of Pyronaridine-artesunate for the Treatment in Uncomplicated Falciparum Malaria
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
March 1, 2015 (Actual)
Primary Completion Date
December 1, 2015 (Actual)
Study Completion Date
June 1, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
Collaborators
NCHADS - Ministry of Health of Cambodia

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria, Falciparum

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
123 (Actual)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Facility Information:
Facility Name
Tasanh Health Centre, Battambang
City
Battambang
Country
Cambodia
Facility Name
Referral hospital (Pailin)
City
Pailin
Country
Cambodia
Facility Name
Promoy Health Centre (Pursat)
City
Pursat)
Country
Cambodia

12. IPD Sharing Statement

Citations:
PubMed Identifier
26926629
Citation
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.
Results Reference
derived

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

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