Pyronaridine Artesunate (3:1) in Children and Adults With Acute Plasmodium Vivax Malaria

This study has been completed.
Sponsor:
Collaborator:
Shin Poong Pharmaceuticals
Information provided by:
Medicines for Malaria Venture
ClinicalTrials.gov Identifier:
NCT00440999
First received: February 26, 2007
Last updated: January 21, 2009
Last verified: January 2009
  Purpose

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.


Condition Intervention Phase
Malaria
Drug: Pyronaridine artesunate
Drug: Chloroquine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Medicines for Malaria Venture:

Primary Outcome 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 Outcome 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.

Estimated Enrollment: 456
Study Start Date: March 2007
Study Completion Date: September 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   3 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00440999

Locations
Cambodia
Pailin Referral Hospital
Pailin, Pailin Province, Cambodia
India
Wentlock District Hospital
Mangalore, India
Indonesia
RSUD TC Hillers
Maumere, Nusa Tenggara Timur, Indonesia, 86113
Thailand
MaeLamad District Hospital
MaeLamad, Tak Province, Thailand
MaeSod General Hospital
MaeSod, Tak Province, Thailand
Sponsors and Collaborators
Medicines for Malaria Venture
Shin Poong Pharmaceuticals
Investigators
Study Director: Isabelle Borghini Fuhrer, PhD Medicines for Malaria Venture
  More Information

Additional Information:
No publications provided by Medicines for Malaria Venture

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00440999     History of Changes
Other Study ID Numbers: SP-C-006-06
Study First Received: February 26, 2007
Last Updated: January 21, 2009
Health Authority: Indonesia: Food and Drug Control Agency (BPOM)
Cambodia: Ministry of Health
India: Ministry of Health
Thailand: Ministry of Public Health

Keywords provided by Medicines for Malaria Venture:
P vivax
malaria
ACT

Additional relevant MeSH terms:
Malaria
Malaria, Vivax
Protozoan Infections
Parasitic Diseases
Artesunate
Chloroquine
Chloroquine diphosphate
Pyronaridine
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 18, 2014