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CompletedNCT03201770Updated Jun 26, 2019

Cohort Event Monitoring Study of Pyramax®

A Phase 4 interventional study of pyronaridine artesunate in Malaria,Falciparum, sponsored by Shin Poong Pharmaceutical Co. Ltd.. Completed at 5 sites in 5 countries. Open to participants aged 3 Months and older. Per ClinicalTrials.gov, last updated 2019-06-26.

Sponsored by Shin Poong Pharmaceutical Co. Ltd. · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
8,572
Allocation
Not applicable
Ages
3 Months and older
Sex
All
01

Study summary

The study is to be performed in public health facilities in Central and West Africa where Pyramax will be used as treatment of uncomplicated malaria episodes, including repeat episodes. The study is to assess the safety of Pyramax, particularly in patients with underlying liver function abnormalities, in patients who have co-morbid conditions, such as HIV, and also in very small children (\<1 year of age).

Read the detailed description

This is a non-comparative Cohort Event Monitoring study. The study will assess the safety of Pyramax in terms of the evaluation and identification of the hepatic safety events in a sub group of patients enrolled with liver function tests (LFT)s >2x upper limit of normal (ULN) from blood taken immediately prior to treatment without any clinical signs or symptoms of hepatotoxicity and with signs and symptoms of uncomplicated malaria confirmed by a Rapid Diagnostic Test (RDT) or microscopy (thick blood smear). The study will compare the clinical hepatic safety of Pyramax between a cohort of patients enrolled with LFTs >2xULN and a cohort of patients enrolled with normal LFTs matched for demographic characteristics.

An estimated 8,572 malaria episodes are to be recruited to provide 120 malaria episodes in patients with baseline raised LFTs >2xULN for follow up of liver function. A cohort of at least 2% of children who are \<1 year of age will be included for monitoring of liver function.

02

Conditions studied

  • Malaria,Falciparum

Keywords

  • Uncomplicated Malaria
  • Pyramax
  • Pyronaridine artesunate
03

Who can participate

Ages eligible
3 Months and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Uncomplicated malaria (Plasmodia of any species) diagnosed as per national policies and in line with WHO recommendations:

    • Fever or history of fever in the previous 24 h and/or the presence of anaemia, for which pallor of the palms appears to be the most reliable sign in young children.
    • Confirmation of malaria by a parasitological diagnosis (RDT or Microscopy (thick blood smear). analysis).
  • Weight ≥5 kg - \< 20 kg (granules); ≥20 kg (tablets).
  • Ability to take an oral medication.
  • Ability and willingness to participate based on signed informed consent (a parent or a guardian has to sign for children below 18 years old) and on signed assent form for minors that could be required per national regulations in each participating country.
  • The patient has to comply with all scheduled follow-up visits.

Exclusion criteria

Exclusion Criteria:

  • Patients with clinical signs or symptoms of hepatic injury (such as nausea, abdominal pain associated with jaundice) or known severe liver disease (i.e. decompensated cirrhosis, Child-Pugh stage 3 or 4).
  • Known allergy to artemisinin and/or to pyronaridine.
  • Known pregnancy.
  • Lactating women should be excluded if other anti-malarial treatments are available.
  • Complicated malaria as per WHO definition (Annex 2)
  • Patients that the investigator considers would be at particular risk if receiving an anti-malarial or if participating in the study.
  • Patients having been treated with Pyramax in the previous 28 days.
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
8,572 participants (actual)

Study arms

  • Experimental
    Pyramax

    Pyronaridine artesunate tablets (180/60mg) and granules (60/20mg)

    Drug: pyronaridine artesunate

Interventions

  • Drugpyronaridine artesunate

    Antimalarial treatment

    Also known as: Pyramax

05

What researchers measure

Primary outcomes

  1. Evaluation and identification of hepatic safety events, including raised liver function tests

    Evaluation and identification of hepatic safety events (including raised liver function tests - LFTs) of Pyramax in a sub group of malaria patients enrolled with LFTs \>2xUL.

    Time frame: Assessment up to Day 28.

Secondary outcomes

  1. Overall safety

    Evaluation of the adverse event reporting of Pyramax in the treatment of uncomplicated malaria under real life conditions.

    Time frame: Assessment up to Day 28.

  2. Evaluation of Efficacy

    Evaluation of the efficacy based on crude Day 28 cure rate by species and PCR adjusted cure rate for Day 28 cure rate for P. falciparum of Pyramax in the treatment of uncomplicated malaria under real life conditions

    Time frame: Assessment up to Day 28.

06

Study locations

5 sites
  • The Biotechnology Center Nkolbisson, Univ of Yaounde I, Messa
    Yaoundé, Cameroon
  • Centre de Recherche du Centre Hospitalier du Mont Amba
    Kinshasa, XI, Congo, The Democratic Republic of the
  • Centre de Santé FCRM, Hospital of Talangai
    Brazzaville, Congo
  • Institut Pierre Richet / Institut National de SanPublique (IPR/INSP)
    Bouaké, BP 1500, Côte D'Ivoire
  • CERMEL, Albert Schweitzer Hospital
    Lambaréné, BP 118, Gabon
07

References and documents

Publications

  • Koehne E, Zander N, Rodi M, Held J, Hoffmann W, Zoleko-Manego R, Ramharter M, Mombo-Ngoma G, Kremsner PG, Kreidenweiss A. Evidence for in vitro and in vivo activity of the antimalarial pyronaridine against Schistosoma. PLoS Negl Trop Dis. 2021 Jun 24;15(6):e0009511. doi: 10.1371/journal.pntd.0009511. eCollection 2021 Jun. Erratum In: PLoS Negl Trop Dis. 2022 Jun 2;16(6):e0010512. doi: 10.1371/journal.pntd.0010512. PubMed 34166393 ↗
  • Tona Lutete G, Mombo-Ngoma G, Assi SB, Bigoga JD, Koukouikila-Koussounda F, Ntamabyaliro NY, Ntoumi F, Agnandji ST, Groger M, Shin J, Borghini-Fuhrer I, Arbe-Barnes S, Allen SJ, Kremsner PG, Miller R, Duparc S, Ramharter M; CANTAM study group. Pyronaridine-artesunate real-world safety, tolerability, and effectiveness in malaria patients in 5 African countries: A single-arm, open-label, cohort event monitoring study. PLoS Med. 2021 Jun 15;18(6):e1003669. doi: 10.1371/journal.pmed.1003669. eCollection 2021 Jun. PubMed 34129601 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03201770
Lead sponsor
Shin Poong Pharmaceutical Co. Ltd.
Collaborators
Medicines for Malaria Venture
Responsible party
Sponsor
First posted
Jun 28, 2017
Start date
Jun 22, 2017
Primary completion
Apr 10, 2019
Completion
Apr 10, 2019
Last update
Jun 26, 2019

Study contacts

Michael Ramharter, MD, DTM&H
principal investigator · CERMEL, University of Tübingen, Germany

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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