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Pyronaridine Artesunate 3:1 Granule Formulation vs. Coartem© Crushed Tablets in P. Falciparum Malaria Pediatric Patients

This study has been completed.
Sponsor:
Collaborator:
Shin Poong Pharmaceuticals
Information provided by:
Medicines for Malaria Venture
ClinicalTrials.gov Identifier:
NCT00541385
First received: October 9, 2007
Last updated: January 21, 2009
Last verified: January 2009

October 9, 2007
January 21, 2009
October 2007
September 2008   (final data collection date for primary outcome measure)
PCR corrected ACPR on Day 28 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
The primary objective of this clinical study is to demonstrate the efficacy of a fixed combination of pyronaridine artesunate (PA) granule formulation (60:20 mg) by showing a PCR-corrected adequate clinical and parasitological cure rate of more than 90%. [ Time Frame: 42 days after first dosing ]
Complete list of historical versions of study NCT00541385 on ClinicalTrials.gov Archive Site
  • PCR-corrected ACPR on Day 14 [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
  • Incidence and severity of adverse events and of cllinically significant laboratory results, ECG, vital signs or physical examination abnormalities [ Time Frame: Day 28 and Day 42 ] [ Designated as safety issue: Yes ]
Secondary objectives: - To compare the efficacy (non-inferiority) and safety of PA granule formulation compared to Coartem® crushed tablets in a paediatric population. - To asses the safety of PA granule formulation. [ Time Frame: 42 days ]
Not Provided
Not Provided
 
Pyronaridine Artesunate 3:1 Granule Formulation vs. Coartem© Crushed Tablets in P. Falciparum Malaria Pediatric Patients
Phase III Comparative, Open-Labelled, Randomised, Clinical Study to Assess a Fixed Dose of Oral Pyronaridine Artesunate Granule Formulation vs. Coartem® Crushed Tablets in Infants With Acute Uncomplicated Plasmodium Falciparum Malaria
  • The primary objective of this clinical study is to demonstrate the efficacy of the fixed combination of pyronaridine artesunate granule formulation (60:20 mg; paediatric PYRAMAX®) by showing a PCR-corrected adequate clinical and parasitological cure rate of more than 90%.
  • Treatment success or failures will be classified according to WHO Guidelines 2005

The need for safe and efficacious anti-malarial treatments for infants and children is huge given that they are the major group affected by acute uncomplicated malaria. There are relatively few paediatric formulations of artemisinin combination therapies. In addition to the tablet formulation of pyronaridine artesunate (PA) (PYRAMAX), Shin Poong Pharm Co is developing a paediatric dosing form presented as a granule formulation, packed in appropriate aluminium sachets each containing 60mg pyronaridine tetraphosphate and 20mg artesunate.

This Phase III study is designed to demonstrate that the efficacy of PA granule formulation, as assessed in terms of PCR-corrected APCR, is above 90% and subsequently to compare (non-inferiority) the efficacy and safety of PA granule formulation to Coartem® crushed tablets in infants and children.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Malaria
  • Drug: pyronaridine artesunate
    The strength of the granule formulation is 60:20 mg pyronaridine artesunate per sachet. Depending on their body weight, patients will receive between 1 to 3 pyronaridine artesunate sachets per day, for 3 consecutive days The actual dose-range covered by this regimen is 7.0:2.3 mg/kg to 13.3:4.4 mg/kg pyronaridine artesunate, which has shown to be effective and safe in the phase II studies conducted in children and adults.
    Other Name: Pyramax
  • Drug: arthemeter lumefantrine

    Artemether 20 mg and lumefantrine 120 mg fixed dose combination, 6 dose regimen 120 mg artemether and 720 mg lumefantrine total (Novartis).

    The posology is twice daily for 3 consecutive days 1 tablet for patients weighing ≥5 kg to <15 kg, 2 tablets for patients weighing ≥15 to <25 kg.

    Other Name: Coartem
  • Experimental: 1
    60mg pyronaridine and 20mg artesunate fixed dose combination granule formulation for 3 consecutive days
    Intervention: Drug: pyronaridine artesunate
  • Active Comparator: 2
    120mg lumefantrine and 20mg Artemether fixed dose combination crushed tablets, twice a day for 3 days
    Intervention: Drug: arthemeter lumefantrine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
534
November 2008
September 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Male or female patients ≤12 years of age.
  2. Body weight ≥ 5 kg and < 25 kg with no clinical evidence of severe malnutrition (defined as a child whose weight-for-height is below -3 standard deviations or less than 70% of the median of the NCHS/WHO normalised reference values).
  3. Presence of acute uncomplicated P. falciparum mono-infection confirmed by:

    1. Fever, as defined by axillary temperature ≥ 37.5°C or oral/tympanic/rectal temperature ≥ 38°C, or documented history of fever in the previous 24 hours and,
    2. Positive microscopy of P. falciparum with parasite density between 1,000 and 200,000 asexual parasite count/µl of blood.
  4. Written informed consent, in accordance with local practice, provided by parent/guardian. If the parent/guardian is unable to write, witnessed consent is permitted according to local ethical considerations. Where possible, patient assent will be sought.
  5. Ability to swallow whole volume of liquid in which medication is suspended.
  6. 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.
  7. Ability and willingness to participate based on information given to parent or guardian and access to health facility. The patient is to comply with all scheduled follow up visits until D42.

Exclusion Criteria:

  1. Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization Criteria 2000 [Attachment 3].
  2. Mixed Plasmodium infection.
  3. Severe vomiting, defined as more than three times in the 24 hours prior to inclusion in the study or inability to tolerate oral treatment, or severe diarrhoea defined as 3 or more watery stools per day.
  4. Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval greater or equal to 450 milliseconds), respiratory (including active tuberculosis), history of jaundice, hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric, history of convulsions or other abnormality (including recent head trauma).
  5. Presence of significant anaemia, as defined by Hb < 8 g/dL.
  6. Presence of febrile conditions caused by diseases other than malaria.
  7. Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, lumefantrine or artesunate or other artemisinins.
  8. Patients with known disturbances of electrolytes balance, e.g., hypokalaemia or hypomagnesaemia.
  9. Use of any other antimalarial agent within 2 weeks prior to start of the study as evidenced by reported patient history.
  10. Pregnant or breast feeding.
  11. Patients taking any drug which is metabolised by the cytochrome enzyme CYP2D6 (flecainide, metoprol, imipramine, amitriptyline, clomipramine).
  12. Received an investigational drug within the past 4 weeks.
  13. Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab).
  14. Known positive for HIV antibody.
  15. Liver function tests [ASAT/ALAT levels] more than 2.5 times upper limit of normal range.
  16. Known significant renal impairment as indicated by serum creatinine of more than 1.4 mg/dL.
  17. Previous participation in any clinical study with pyronaridine artesunate.
Both
up to 12 Years
No
Contact information is only displayed when the study is recruiting subjects
Burkina Faso,   Congo,   Côte D'Ivoire,   Gabon,   Kenya,   Mali,   Mozambique,   Philippines
 
NCT00541385
SP-C-007-07
Yes
Isabelle Borghini Fuhrer, Medicines for Malaria Venture
Medicines for Malaria Venture
Shin Poong Pharmaceuticals
Study Director: Claude Oeuvray, PhD Medicines for Malaria Venture
Medicines for Malaria Venture
January 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP