Pyronaridine Artesunate-Ritonavir Drug-drug Interaction Study
Condition: Malaria
MeSH terms: Malaria
Intervention: Ritonavir and Pyramax; Pyramax
Intervention description: 100 mg ritonavir (one soft gelatin capsule twice per day over 17 days, the evening capsule on day 1 will be omitted) and Pyramax (pyronaridine/artesunate) 180:60 mg (3 to 4 tablets once per day according to weight for 3 days).; Pyramax (pyronaridine/artesunate) 180:60 mg (3 to 4 tablets once per day according to weight for 3 days).
Intervention MeSH terms: Ritonavir; Artesunate; Pyronaridine; Pyronaridine tetraphosphate, artesunate drug combination
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: malaria; artemisinin-based combination therapy (ACT); antimalarial; pyronaridine artesunate (Pyramax)

Summary:

      The primary objective of the study is to determine any drug interaction between the
      antimalarial Pyramax (pyronaridine artesunate) and the protease inhibitor ritonavir in
      healthy subjects. The secondary objective of the study is to assess further the safety of
      Pyramax in this setting.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female subjects between the ages of 18 and 55 years with a body weight between
             50 and 90 kg and a body mass index calculated using Quetelet's Index - weight
             (kg)/height (m2) between 18.5-30.0

          2. Signed and dated a 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. 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)

          6. Female subjects of childbearing potential with a negative urine pregnancy test at
             screening and a negative plasma pregnancy test prior to inclusion and who agreed to
             one of the following methods:

               -  Double barrier method of contraception for 2 weeks before first study drug
                  administration and throughout the entire study follow up period

               -  Partner(s) who had undergone vasectomy and has been negative for sperm for at
                  least 6 months

          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 clinical abnormality

          2. Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or
             artesunate or other artemisinins or ritonavir

          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 any clinical study in last 2 months