NCT00422084

Brief Summary

The primary objective of this phase III study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) with that of Coartem® (artemether lumefantrine, AL) in children and adults with uncomplicated P falciparum malaria in Africa and South East Asia.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,272

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jan 2007

Shorter than P25 for phase_3

Geographic Reach
9 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2007

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

January 12, 2007

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 15, 2007

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2008

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2008

Completed
13.4 years until next milestone

Results Posted

Study results publicly available

September 20, 2021

Completed
Last Updated

November 2, 2021

Status Verified

October 1, 2021

Enrollment Period

1.2 years

First QC Date

January 12, 2007

Results QC Date

August 20, 2021

Last Update Submit

October 22, 2021

Conditions

Malaria

Keywords

malariaantimalarialartemisinin based combination therapy (ACT)P. falciparumpyronaridine artesunate (Pyramax)

Outcome Measures

Primary Outcomes (1)

  • PCR-Corrected Adequate Clinical and Parasitological Response (ACPR) Rate on 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 (7)

  • PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 14

    Day 14

  • Crude ACPR (Non-PCR Corrected ACPR) on Day 14 and Day 28

    Day 14 and 28

  • Parasite Clearance Time

    Days 0, 3, 7, 14, 21, 28, 35, and 42 (or on any other day if the subject spontaneously returned)

  • Fever Clearance Time

    Day 0 and every 8 hours over ≥72 hours following first study drug administration or temperature normalization for ≥2 readings between 7 and 25 hours apart, then at each visit and as clinically indicated

  • Percentage of Patients With Fever Clearance at Day 1, 2 and 3

    Days 1, 2, 3

  • +2 more secondary outcomes

Study Arms (2)

PA group

EXPERIMENTAL

Pyronaridine artesunate (PA)

Drug: Pyronaridine artesunate

AL group

ACTIVE COMPARATOR

Arthemether lumefantrine (AL)

Drug: Coartem® (artemether lumefantrine)

Interventions

Pyronaridine artesunateDRUG

Oral PA (180:60mg tablets) once a day plus AL-placebo (twice a day) for 3 consecutive days (Day 0, 1, and 2)

Also known as: Pyramax
PA group
Coartem® (artemether lumefantrine)DRUG

AL (20:120mg tablets) twice a day plus PA-placebo (once a day) for 3 consecutive days (Day 0, 1, and 2)

Also known as: Coartem
AL group

Eligibility Criteria

Age3 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Male or female patients between the age of 3 and 60 years, inclusive.
  • Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition.
  • Presence of acute uncomplicated P. falciparum mono-infection confirmed by:
  • Fever, as defined by axillary/tympanic temperature ≥ 37.5°C or oral/rectal temperature ≥ 38°C, or documented history of fever in the previous 24 hours and,
  • Positive microscopy of P. falciparum with parasite density between 1,000 and 100,000 asexual parasite count/μl of blood.
  • Written informed consent, in accordance with local practice, provided by patient and/or parent/guardian/spouse.
  • Ability to swallow oral medication.

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.
  • Severe vomiting or severe diarrhoea.
  • Known history or evidence of clinically significant disorders.
  • Presence of significant anaemia, as defined by Hb \<8 g/dL.
  • Presence of febrile conditions caused by diseases other than malaria.
  • Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, lumefantrine or artesunate or other artemisinins.
  • Patients with known disturbances of electrolytes balance, e.g., hypokalaemia or hypomagnesaemia.
  • Use of any other antimalarial agent within 2 weeks prior to start of the study as evidenced by a positive urine test.
  • Female patients of child-bearing potential must be neither pregnant (as demonstrated by a negative pregnancy test) nor lactating, and must be willing to take measures to not become pregnant during the study period.
  • Patients taking any drug which is metabolised by the cytochrome enzyme CYP2D6 (flecainide, metoprol, imipramine, amitriptyline, clomipramine).
  • 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 the upper limit of normal range.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Ecole de Santé Publique, Faculté de Médecine, Université de Kinshasa

Kinshasa, Democratic Republic of the Congo

Location

Komfo Anoykye Teaching Hospital

Kumasi, Ghana

Location

RSUD TC Hillers

Maumere, Nusa Tenggara Timur, 86113, Indonesia

Location

Jayapura General Hospital (RSUD) DOK II

Jayapura, Special Region of Papua, Indonesia

Location

Siaya District Hospital, Medical Superintendent's office

Siaya, Kenya

Location

Malaria Research and Training Center, Faculté de Médecine, de Pharmacie et d'Ondonto-stomatologie

Bamako, Mali

Location

Instituto Nacional de Saude, Ministero de Saude

Maputo, Mozambique

Location

Puerto Princesa General Hospital

Puerto Princesa City, Philippines

Location

Service de Parasitologie, Faculté de Médecine, Université Cheikh Anta Diop

Dakar, Dakar Fann, Senegal

Location

Farafenni Field Station, c/o: MRC Laboratories

Fajara, The Gambia

Location

Related Publications (4)

  • Tshefu AK, Gaye O, Kayentao K, Thompson R, Bhatt KM, Sesay SS, Bustos DG, Tjitra E, Bedu-Addo G, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L; Pyronaridine-artesunate Study Team. Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial. Lancet. 2010 Apr 24;375(9724):1457-67. doi: 10.1016/S0140-6736(10)60322-4.

    PMID: 20417857RESULT

  • Pryce J, Taylor M, Fox T, Hine P. Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria. Cochrane Database Syst Rev. 2022 Jun 21;6(6):CD006404. doi: 10.1002/14651858.CD006404.pub4.

    PMID: 35726133DERIVED

  • Ayyoub A, Methaneethorn J, Ramharter M, Djimde AA, Tekete M, Duparc S, Borghini-Fuhrer I, Shin JS, Fleckenstein L. Population Pharmacokinetics of Pyronaridine in Pediatric Malaria Patients. Antimicrob Agents Chemother. 2015 Dec 14;60(3):1450-8. doi: 10.1128/AAC.02004-15.

    PMID: 26666916DERIVED

  • 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: 23433102DERIVED

MeSH Terms

Conditions

Malaria

Interventions

pyronaridine tetraphosphate, artesunate drug combinationArtemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical Preparations

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

  • Claude Oeuvray, PhD

    Medicines for Malaria Venture

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 12, 2007

First Posted

January 15, 2007

Study Start

January 1, 2007

Primary Completion

April 1, 2008

Study Completion

May 1, 2008

Last Updated

November 2, 2021

Results First Posted

September 20, 2021

Record last verified: 2021-10

Locations

DE(1)TH(1)MO(1)PH(1)MA(1)SE(1)ID(2)GH(1)KE(1)