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Safety and Efficacy of Pyronaridine Artesunate Versus Chloroquine in Children and Adult Patients With Acute Plasmodium Vivax Malaria

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04368910
Recruitment Status : Terminated (Due to slow recruitment the study was terminated prematurely by the Sponsor after 30 subjects had been included)
First Posted : April 30, 2020
Last Update Posted : April 30, 2020
Sponsor:
Collaborator:
Shin Poong Pharmaceuticals
Information provided by (Responsible Party):
Medicines for Malaria Venture

Brief Summary:
The primary objective of this clinical 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 (P. vivax) malaria

Condition or disease Intervention/treatment Phase
Malaria Drug: Pyronaridine - artesunate Drug: Chloroquine Phase 3

Detailed Description:
This Phase III study was designed to meet regulatory requirements for registration of pyronaridine artesunate in Korea. A comparative study was implemented using chloroquine as a comparator. The comparator in this study, chloroquine, is recognized as an effective and well-tolerated anti-malarial therapy, and is standard blood-stage therapy for subjects with P. vivax malaria in Korea. It was anticipated that the study results would be pooled with the results of study SP-C-006-06 entitled "A Phase III multicenter, randomized, 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" for a formal non-inferiority analysis.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III 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 in Korea With Acute Plasmodium Vivax Malaria
Actual Study Start Date : September 6, 2007
Actual Primary Completion Date : October 16, 2010
Actual Study Completion Date : November 15, 2010


Arm Intervention/treatment
Experimental: Pyronaridine - artesunate

Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.

For patients who complete the study up to Day 28 and who have normal G-6-PD activity, a 14-day course of primaquine (15 mg/day) shall be administered starting on Day 28, after all required assessments have been performed, to complete their radical cure. Patients who are deficient in G-6-PD and who complete the study up to Day 28 will be treated as per country policy.

Drug: Pyronaridine - artesunate
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
Other Name: Pyramax

Active Comparator: Chloroquine

Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.

For patients who complete the study up to Day 28 and who have normal G-6-PD activity, a 14-day course of primaquine (15 mg/day) shall be administered starting on Day 28, after all required assessments have been performed, to complete their radical cure. Patients who are deficient in G-6-PD and who complete the study up to Day 28 will be treated as per country policy.

Drug: Chloroquine
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.




Primary Outcome Measures :
  1. Cure rate on Day 14 [ Time Frame: Day 14 ]
    No parasitaemia on Day 14 irrespective of axillary temperature without previously meeting any of the criteria of treatment failure


Secondary Outcome Measures :
  1. Cure rate on Day 28 [ Time Frame: Day 28 ]
    No parasitaemia on Day 28 irrespective of axillary temperature without previously meeting any of the criteria of treatment failure

  2. Parasite clearance time (PCT) [ Time Frame: Day 0 to Day 42 ]
    Parasite clearance was defined as zero presence of asexual parasites for 2 consecutive negative readings taken between 7 and 25 hours apart

  3. Fever clearance time (FCT) [ Time Frame: Day 0 to Day 42 ]
    Time from first dosing to first normal reading of temperature (<37.5°C for axillary/tympanic or <38°C for oral/rectal) for 2 consecutive normal temperature readings taken between 7 and 25 hours apart

  4. Proportion of patients who had cleared parasite on Days 1, 2, and 3 [ Time Frame: Day 1, Day 2 and Day 3 ]
    Proportion of patients who had cleared parasite

  5. Proportion of patients who had cleared fever on Days 1, 2, and 3 [ Time Frame: Day 1, Day 2 and Day 3 ]
    Proportion of patients who had cleared fever

  6. Incidence of AEs and of clinically significant laboratory results, electrocardiogram (ECG), vital signs or physical examination abnormalities [ Time Frame: Day 0 to Day 42 ]
    Incidence of AEs and (including clinically significant laboratory results, electrocardiogram (ECG), vital signs or physical examination abnormalities)


Other Outcome Measures:
  1. Proportion of patients with PCR-corrected cure on Days 14, 28 and 42 [ Time Frame: Day 14, Day 28, and Day 42 ]
    Proportion of subjects with PCR-corrected cure

  2. Cure rate on Day 42 [ Time Frame: Day 0 to Day 42 ]
    Cure rate and PCR-corrected cure rate



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   3 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
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:

    1. 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,
    2. Positive microscopy of P. vivax with parasite density ≥250/ μL 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04368910


Locations
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Korea, Republic of
Inje University Ilsan Paik Hospital
Goyang-si, Korea, Republic of, 411-706
Eulji General Hospital
Seoul, Korea, Republic of, 139-711
Sponsors and Collaborators
Medicines for Malaria Venture
Shin Poong Pharmaceuticals
Investigators
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Study Director: Stephan Duparc, MD Medicine for Malaria Venture
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Responsible Party: Medicines for Malaria Venture
ClinicalTrials.gov Identifier: NCT04368910    
Other Study ID Numbers: SP-C-008-07
First Posted: April 30, 2020    Key Record Dates
Last Update Posted: April 30, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Medicines for Malaria Venture:
Malaria
Pyramax
Pyronaridine artesunate
Chloroquine
Children
Adults
Plasmodium vivax
Republic of Korea
Additional relevant MeSH terms:
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Malaria
Malaria, Vivax
Protozoan Infections
Parasitic Diseases
Artesunate
Chloroquine
Pyronaridine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics
Amebicides
Antirheumatic Agents