Relative Bioavailability of Pyronaridine-artesunate in Tablet and Granule Formulations in Healthy Volunteers
Condition: Malaria
MeSH terms: Malaria
Intervention: Pyronaridine-artesunate granules; Pyronaridine-artesunate tablets
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: 60.0
Sex: All
Minimum age: 20 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pyronaridine artesunate tablet; Pyronaridine artesunate granules; Pyramax tablet; Pyramax granules; Bioavailability; artemisinin based combination therapy (ACT)

Summary:

      The primary objective of this study is to compare the bioavailability of two formulations
      (tablets and granules for dispersion) of the antimalarial drug pyronaridine-artesunate [3:1]
      (Pyramax, PA) in healthy adults. The secondary objective is to compare the safety of the two
      PA formulations and liver function test changes following the first and second
      administrations.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy male and/or female subjects between the ages of 20 and 45 years, inclusive.
             (Healthy is defined as no clinically relevant abnormalities identified by a detailed
             medical history, full physical examination, including blood pressure and pulse rate
             measurement, 12-lead ECG and clinical laboratory tests)

          -  Weight between 50 kg and 80 kg and Body Mass Index (BMI) calculated using Quetelet's
             Index - weight(kg)/height (m2) between 18.5 to 27 kg/m2;

          -  An informed consent document signed and dated by the subject (prior to screening and
             any study activities, including discontinuation of any prohibited medications)

          -  Strictly normal values of alanine aminotransferase(ALT), aspartate aminotransferase
             (AST), and bilirubin, and normal or abnormal but clinically insignificant results of
             the other blood and urine laboratory parameters at screening.

          -  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) or who has undergone sterilization (via hysterectomy or bilateral
             tubal ligation)]

          -  Female subjects of childbearing potential with a negative urine pregnancy test at
             screening, and a negative pregnancy blood test on admission, and who :

               -  agree to double barrier method of contraception for 4 weeks before first study
                  drug administration and throughout the entire study follow up period, or

               -  whose partner has undergone vasectomy and has been negative for sperm for at
                  least 6 months

          -  Subjects who are willing and able to comply with scheduled visits, treatment plan,
             laboratory tests, and other study procedures.

        Exclusion Criteria:

          -  Known history or evidence of clinically significant disorders such as cardiovascular
             (including arrhythmia, acute corrected QT interval (QTc) greater or equal to 450
             milliseconds), 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)

          -  Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or
             artesunate or other artemisinins

          -  Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or
             Hepatitis C antibody (HCV Ab)

          -  Seropositive HIV antibody, seropositive syphilis [Syphilis reagin test (+)]

          -  Previous exposure to pyronaridine-artesunate (Pyramax)

          -  Present or recent history (last two years) of tobacco abuse (≥10 cigarettes/day)

          -  Known or suspected alcohol abuse or illicit drug use up to 5 years before the study
             start or positive findings on urine drug screen

          -  Intake of alcoholic beverages or caffeine-containing food or beverages, such as
             coffee, tea, chocolate, or cola, 48 hours before study drug administration

          -  Intake of grapefruit, Seville oranges or products containing these from 72 hours
             before the start of study drug administration

          -  Gilbert's disease

          -  Use of over-the-counter (OTC) medications, including vitamins, analgesics,
             antipyretics or antacids within 7 days before study drug administration

          -  Use of prescription medications within 14 days before the start of study drug
             administration or required chronic use of any prescription medication

          -  Use of enzyme-altering agents (e.g. barbiturates, phenothiazines, cimetidine, etc.)
             within 30 days before the start of study drug administration

          -  Plasma donation within 60 days before the start of study drug administration

          -  Blood donation of 500 mL or more within 60 days before the start of study drug
             administration

          -  Participation AND having had drug administration in any other clinical study within
             the 60 days before start of study drug administration