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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
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)
Cross Research S.A., Phase I Unit
Arzo, Switzerland
Pyronaridine Pharmacokinetics: Tmax, Half-life
Tmax: time to maximum concentration Half-life: computed as ln (2)/kel
Time frame: Sampling performed at predose at 0 h and at, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12, 24, 48, 72 h and on Day 5, 7, 14, 21, 28, 35, 42 for each period
Pyronaridine (PP), Artesunate (AS), Dihydroartemisinin (DHA) Pharmacokinetics: Cmax
Cmax: maximum peak observed concentration
Time frame: PP sampling performed at predose at at 0 h and at, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12, 24, 48, 72 h and on Day 5, 7, 14, 21, 28, 35, 42 for each period AS, DHA sampling performed at predose at 0 h and at 0.25, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12 h for each period
Artesunate (AS) and Dihydroartemisinin (DHA) Pharmacokinetics: Tmax, Half-life
Tmax: time to maximum concentration Half-life: computed as ln (2)/kel
Time frame: Sampling performed at predose at 0 h and at 0.25, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12 h for each period
Pyronaridine Pharmacokinetics: AUC0-last, AUC0-∞
AUC0-last: Area under the concentration-time curve from time 0 (0 h) through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn AUC0-∞: Area under the concentration-time curve from time 0 (0 h) to infinity, computed using the linear trapezoidal rule as AUClast + CLQCT / Kel
Time frame: Sampling performed at predose at 0 h and at, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12, 24, 48, 72 h and on Day 5, 7, 14, 21, 28, 35, 42 for each period
Artesunate (AS) and Dihydroartemisinin (DHA): AUC0-last, AUC0-∞
AUC0-last: Area under the concentration-time curve from time 0 (0 h) through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn AUC0-∞: Area under the concentration-time curve from time 0 (0 h) to infinity, computed using the linear trapezoidal rule as AUClast + CLQCT / Kel
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Time frame: Sampling performed at predose at 0 h and at 0.25, 0.5, 1, 1.5, 2.5, 4, 6, 8, 12 h for each period