Human Mass Balance Study of Pyronaridine
Condition: Malaria
MeSH terms: Malaria
Intervention: 14C-labeled Pyronaridine
Intervention description: Single dose of 720 mg Pyronaridine together with 14C-Pyronaridine (approx. 100 µg, 800 nCi).
Intervention MeSH terms: Pyronaridine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: Male
Minimum age: 40 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Mass Balance; Accelerated Mass Spectrometry (AMS); microdose; Focus of the study: ADME

Summary:

      The combination of pyronaridine and artesunate is an antimalarial therapy in development.
      This mass balance study is intended to determine the rate and extent of excretion of total
      radioactivity in urine and feces following administration of a single oral micro-dose of
      14C-pyronaridine in humans.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male subjects between the ages of 40 and 55 years with a body weight between 60 and 90
             kg and a body mass index calculated using Quetelet's Index - weight (kg)/height2 (m2)
             between 18.5 - 30.0

          2. Signed and dated written informed consent form (ICF) 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 investigator

          4. Strictly normal values of ALT, AST and bilirubin and normal or abnormal and clinically
             insignificant results (if agreed by the Investigator and the Sponsor on a case by case
             evaluation) of the other blood and urine laboratory parameters at screening

          5. All sexually active male subjects and their partners are willing to undergo
             contraception as follows:

             All male subjects, including those who are sterilised (i.e., vasectomy), should use a
             condom. Their female partner must also use at least 1 of the medically acceptable
             forms of contraceptives listed below. Male subjects must not donate sperm or have
             unprotected sex during the study and until 87 days after taking the dose of
             investigational product.

             Medically acceptable contraceptives for this study are:

             Condoms in addition to:

               -  Intrauterine devices

               -  Hormonal contraceptives (oral, depot, patch, injectable, or vaginal ring)

               -  Diaphragms with spermicidal cream or gel

               -  Cervical cap with spermicidal cream or gel

               -  Spermicidal foam

          6. 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 clinical abnormality

          2. Known history of hypersensitivity, allergic or adverse reactions to Pyronaridine

          3. Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or
             Hepatitis C antibody (HCV Ab)

          4. Seropositive HIV antibody

          5. Previous participation in any clinical study with Pyramax

          6. Presence or recent history (last two years) of tobacco abuse (≥10 cigarettes/day)

          7. Known or suspected alcohol abuse or illicit drug use in the last 10 years before the
             study start or positive findings on urine drug screen

          8. Intake of grapefruit and grapefruit juice alcoholic beverages or caffeine-containing
             food or beverages, such as coffee, tea, chocolate, or cola, 48 hours before study drug
             administration

          9. Use of over-the-counter (OTC) medications, including vitamins, analgesics, or
             antacids, 1 week 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.)
             within 30 days or 5 half lives, whichever the longer, before the study start

         12. Plasma donation 1 month before the study start

         13. Blood donation of 450 mL or more in the last 3 months before the study start

         14. Participation in other clinical trials during the previous month in which an
             investigational drug or a commercially available drug was tested

         15. Exposure to artificial ionizing radiation in the last 12 months (e.g., x-ray
             investigation, isotope studies)