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

• Status: Completed
• Trial end date: 2008-11-01
• Target enrollment: 0
• Participant gender: All

Summary

• 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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medicines for Malaria Venture
• Collaborator: Shin Poong Pharmaceuticals
• Treatments: Artemether-lumefantrine combination; Artemisinins; Artesunate; Lumefantrine; Pyronaridine

Criteria

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.