Official Title: “A Phase III Multi-Centre, Randomised, Double-Blind, Double-Dummy, Comparative Clinical Study to Assess the Safety and Efficacy of a Fixed-Dose Formulation of Oral Pyronaridine Artesunate (180:60 mg Tablet) Versus Chloroquine (155 mg Tablet), in Children and Adult Patients With Acute Plasmodium Vivax Malaria”

The purpose of this study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (180:60 mg) with that of standard chloroquine therapy in children and adults with acute, uncomplicated Plasmodium vivax malaria.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2008

Artemisinin-based combination therapies (ACTs) are considered today by WHO to be the best anti-malarials in terms of efficacy and lower propensity to resistance. Pyronaridine artesunate is a new ACT in development to treat acute uncomplicated malaria. Pyronaridine and artesunate are antimalarial agents with a history of clinical use both separately and in combination with other drugs. Each drug has powerful blood schizonticidal actions. The aim of a fixed dose combination of pyronaridine and artesunate in the treatment of uncomplicated acute malaria is to provide rapid reduction in parasitemia with once-daily three-day regimen, thereby improving compliance and reducing the risk of recrudescence through the slower elimination of pyronaridine.Importantly, there is a need for new drugs that are efficacious against both P. falciparum and P. vivax, because in areas where both species exist and health systems are undersourced, it is often not possible to distinguish between the two species at the initial diagnosis.

Intervention(s) in this Clinical Trial

• Drug: Pyronaridine artesunate
• Drug: Chloroquine

Primary Measures

• Cure rate on Day 14.
  • Time Frame: Day 14
    
• Incidence of adverse events and of clinically significant laboratory results, ECG, vital signs or physical examination abnormalities.

Secondary Measures

• Cure rate on Days 21 and 28.
  • Time Frame: Day 21 and 28
    
• Parasite clearance time.
• Fever clearance time.
• Proportion of patients who have cleared parasites on days 1, 2 and 3.
• Proportion of patients who have cleared fever on days 1, 2 and 3.

Inclusion Criteria:

• 1. Male or female patients between the age of 3 and 60 years, inclusive.
• 2. Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition.
• 3. Presence of acute uncomplicated P. vivax mono-infection confirmed by:
• Fever, as defined by axillary/tympanic temperature ≥37.5°C or oral/rectal temperature ≥38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,
• Positive microscopy of P. vivax with parasite density ≥250/ mcL of blood (including at least 50% of asexual parasites)
• 4. Written informed consent, in accordance with local practice, provided by patient and/or parent/guardian/spouse. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations.
• 5. Ability to swallow oral medication.
• 6. Ability and willingness to participate based on information given to patient or parent or guardian and access to health facility.

Exclusion Criteria:

• 1. Presence of a mixed Plasmodium infection.
• 2. Presence of other clinical condition requiring hospitalization.
• 3. Presence of significant anaemia, as defined by Hb < 8 g/dL.
• 4. Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval greater than or equal to 450 msec), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric or other abnormality (including recent head trauma).
• 5. Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, chloroquine or artesunate or other artemisinins.
• 6. Known history of hypersensitivity, allergic or adverse reactions to chloroquine, primaquine and related agents.
• 7. Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab).
• 8. Known seropositive HIV antibody.
• 9. Have received any antimalarial treatment in the preceding 2 weeks, as determined by history and, whenever feasible, by screening test.
• 10. Have received antibacterial with known antimalarial activity in the preceding 2 weeks.
• 11. Have received any investigational drug within the past 4 weeks.
• 12. Liver function tests (AST/ALT levels) more than 2.5 times the upper limit of normal range.
• 13. Known significant renal impairment as indicated by serum creatinine levels of more than 1.4 mg/dL.
• 14. 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.
• 15. Previous participation in the present clinical trial with pyronaridine artesunate.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 3 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Medicines for Malaria Venture

Overall Clinical Trial Officials and Contacts

Isabelle Borghini Fuhrer, PhD Study Director Medicines for Malaria Venture  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00440999

Study ID Number: SP-C-006-06

ClinicalTrials.gov Identifier: NCT00440999

Health Authority: Indonesia: Food and Drug Control Agency (BPOM)

Medicines for Malaria Venture

Shin Poong Pharmaceuticals