bioequivalence trial of pyronaridine artesunate to-be-marketed tablet to the clinical trial reference tablet

Conditions: Malaria

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.

this is a phase i, randomized, single dose, two-way cross-over study of two tablet formulations of the combination of pyronaridine and artesunate (180:60 mg). the study will include 42 healthy participants, comprising male and female adults. participants will be randomized to receive either reference tablet formulation or to-be-marketed formulation first and then will be crossed over to receive the opposite intervention. the study will consist of two single dose treatments of 720:240 mg tablets, separated by a washout period of 43 days. participants will go to the clinic the evening before dosing (dosing days were day 0 for period 1 and day 43 for period 2) under fasting condition and remain in the hospital for 24 hours after receiving dosing. participants will stay in the hospital for 24 hours after their arrival at the clinic. they will return to the clinic at day 2, 3, 5, 7, 14, 21, 28, 35 and 42 on an ambulatory basis. at day 43, the dosing for the second sequence will start and a similar schedule of visits will be followed. each participant will be followed-up for an additional 42 days after the start of the second study period, until the final visit (day 85). the total duration of participation is 85 days plus a maximum of 2 weeks screening period.

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

Keywords: malaria anti-malarial pyronaridine pyronaridine artesunate (pyramax) artemisinin based combination therapy (act)