Bioequivalence Trial of Pyronaridine Artesunate To-be-marketed Tablet to the Clinical Trial Reference Tablet
Condition: Malaria
MeSH terms: Malaria
Intervention: pyronaridine artesunate clinical trial reference tablets; pyronaridine artesunate to-be-marketed tablets
Intervention description: Single total oral dose of 720:240 mg (4 tablets of 180:60 mg); Single total oral dose of 720:240 mg (4 tablets of 180:60 mg)
Intervention MeSH terms: Artesunate; Pyronaridine; Pyronaridine tetraphosphate, artesunate drug combination
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Malaria; anti-malarial; pyronaridine; pyronaridine artesunate (Pyramax); artemisinin based combination therapy (ACT)

Summary:

      The primary objective of this study is to determine the bioequivalence of the combination of
      pyronaridine and artesunate (180:60mg) to-be-marketed tablet to the clinical trial reference
      tablet administered as a single total dose of 720:240 mg in healthy adults. The secondary
      objective is to assess the safety of the two formulations.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female subjects between the ages of 18 and 45 years with a body weight between
             55 and 75 kg and a body mass index using Quetelet's Index - weight (kg)/height2 (m2)
             between 18-28

          2. Signed and dated written informed consent form before undergoing any study related
             activities, including discontinuation of any prohibited medications

          3. Medically normal subjects with no significant abnormal findings at the screening
             physical examination as evaluated by the clinical investigator

          4. Normal (or abnormal and clinically insignificant) laboratory values at screening

          5. Female subjects of non-childbearing potential (i.e., physiologically incapable of
             becoming pregnant, including any female who was post-menopausal (i.e., one year
             without menses)

          6. Female subjects of childbearing potential with a negative urine pregnancy test at
             screening and who agreed to one of the accepted forms of contraception

          7. The ability to understand the requirements of the study and willingness to comply with
             all study procedures

        Exclusion Criteria:

          1. Known history or evidence of clinically significant disorders such as cardiovascular
             (including arrhythmia, acute QTc interval greater or equal to 450 mseconds),
             respiratory (including active tuberculosis), hepatic, renal, gastrointestinal,
             immunological (including active HIV-AIDS), neurological (including auditory),
             endocrine, infectious, malignancy, psychiatric or other abnormality (including head
             trauma)

          2. Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or
             artesunate or other artemisinins

          3. Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or
             Hepatitis C antibody (HCV Ab)

          4. Known seropositive HIV antibody

          5. Previous participation in any clinical trial with pyronaridine artesunate

          6. Presence or recent history (last two years) of tobacco abuse (≥10 cigarettes/day)

          7. Known or suspected alcohol abuse or illicit drug use 10 years before the study start
             or positive findings on urine drug screen

          8. Intake of alcoholic beverages or caffeine-containing food or beverages, such as
             coffee, tea, chocolate, or cola, 24 h before study drug administration

          9. Use of over-the-counter (OTC) medications, including vitamins, analgesics, or
             antacids, 72 h before the study start

         10. Use of prescription medications 14 days before the study start or required chronic use
             of any prescription medication

         11. Use of enzyme-altering agents (e.g., barbiturates, phenothiazines, cimetidine, etc.)
             30 days before the study start

         12. Plasma donation 3 months before the study start

         13. Blood donation of 500 mL or more 3 months before the study start

         14. Participation in an investigational drug study 3 months before randomization