Dutasteride Soft Capsule 0.5 mg Relative to Avodart 0.5 mg Soft Capsule

Title A Bioequivalence study of a randomized, open-label, single dose, two-way crossover design with two-period, two-treatment and two-sequence of Dutasteride soft capsule 0.5 mg relative to Avodart 0.5 mg soft capsule in healthy Thai male volunteers under fasting condition.

Objectives The primary objective is to compare the rate and extent of absorption of a generic formulation with that of a reference formulation when given as equal labeled dose. The secondary objective is to evaluate the safety after oral administration of both test and reference formulation in healthy Thai male volunteers.

Study Design Randomized, open-label, single dose, two-way crossover design with two-period, two-treatment and two-sequence under fasting condition and at least 28 days washout period between the doses.

Sample Size 28 Healthy Human Thai male subjects. Two extra subjects if available, may be checked-in on the day of check in of period-I to compensate for any dropout prior to dosing of period-I. These subjects will be dosed if there are dropouts prior to dosing in period-I. If there are no dropouts, these subjects will be checked-out without being dosed after completion of dosing in period-I.

Drug-Product Test-Product: Dutasteride soft capsule 0.5 mg Reference-product: Avodart 0.5 mg soft capsule Manufactured by: DELPHARM POZNAN S.A., Poland

Administration After an overnight fasting at clinical facility of at least 10 hours, each volunteer will receive a single dose of Dutasteride soft capsule 0.5 mg of either test or reference with 250 mL of drinking water. Each volunteer will be allowed to drink water as desire except 1 hour before and after drug administration. The formulation is given in a crossover fashion as per the randomization schedule. After the administration, the subject's oral cavity will be checked by using flashlight to confirm complete medication and fluid consumption by pharmacist.

Blood Schedule In each period, a total of 19 blood samples (approximately 7 mL each) will be collected at Pre-dose (0 hour) \& at 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00, 8.00, 12.00, 24.00, 36.00, 48.00 and 72.00 hours after study drug administration, respectively. The sample collection at 36.00, 48.00 and 72.00 hours after dosing will be on ambulatory basis (i.e. on separate visit).

Sample Collection Blood samples will be collected through an indwelling catheter placed in a vein using disposable syringe or through fresh venipuncture with disposable syringes and needles. Approximately 7 mL blood sample will be withdrawn and transferred to sample collection pre-labeled tubes containing K3EDTA as anticoagulant at each sampling time point. After collection of blood samples from each subject at each time point, samples will be centrifuged at 4000 rpm for 5 minutes at 4±2°C. After centrifugation, the plasma samples will be aliquot into two pre-labeled cryovials for approximately 1 mL per each cryovial. Cryovials containing plasma sample will be stored at -70±10 °C.

Analytical Method Dutasteride plasma concentration will be assayed as per international Guidelines/In-house SOP by using a UPLC-MS/MS method.

Pharmacokinetic Parameters Primary pharmacokinetic parameter: Cmax, AUC0→72 Secondary pharmacokinetic parameter: Tmax, T1/2, Kel, AUC0→t/AUC0→∞ will be determined from the plasma concentration data of analytes.

Statistical Analysis ANOVA, two one-sided tests for bioequivalence, for log-transformed pharmacokinetic parameters Cmax, AUC0→72 will be performed.

Acceptance Criteria for Bioequivalence To be considered as bioequivalent, the 90% CI of Cmax, AUC0→72of Dutasteride of test and reference products should be in the interval of 80.00-125.00% for the log-transformed data.