The purpose of this study is to evaluate the safety, tolerability and Pharmacokinetics/Pharmacodynamics of multiple doses of GCC-4401C in healthy male subjects.
The primary objective is to investigate the safety, tolerability, and pharmacokinetics of multiple doses of GCC-4401C in healthy male subjects. Forty-six subjects are planned for enrollment. The study consists of five cohorts (10 mg, 20 mg, 40 mg, 60 mg, and 80 mg) with eight subjects per cohort. In the 20 mg cohort, six additional subjects will receive rivaroxaban (Xarelto®) 20 mg as an active comparator in open-label fashion. Within each of the five cohorts, six subjects will be randomized to GCC-4401C and two subjects will be randomized to placebo. The secondary objectives of this study are * To characterize the single dose safety, tolerability, and PK after oral administration of GCC-4401C in healthy male subjects. * To characterize the multiple dose pharmacodynamics after oral administration of GCC-4401C in healthy male subjects. * To determine an appropriate dose range and dosing regimen of oral GCC-4401C for subsequent clinical trials. * To compare the PK and PD of GCC-4401C with an active rivaroxaban (Xarelto®)group at 20 mg in healthy male subjects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
46
* Orally active direct factor Xa inhibitor for use in the prevention and treatment of venous thromboembolic disease. * The dose selection for this clinical study was based on the safety, Pharmacokinetics and Pharmacodynamics results of the single dose study. * GCC-4401C was well tolerated in the single ascending dose study up to the highest single oral dose administered of 80 mg from 2.5 mg in 48 subjects. * The study consists of five cohorts (10 mg, 20 mg, 40 mg, 60 mg, and 80 mg) with eight subjects per cohort. * In the 20 mg cohort, six additional subjects will receive rivaroxaban (Xarelto®) 20 mg as an active comparator in open-label fashion.
Rivaroxaban (Xarelto®) 20 mg tablets for oral administration IMP, placebo and comparator will be administered the same time points. The comparator will be administered open-label 30 minutes after a standard breakfast.
PAREXEL Internatonal
Early Phase Clinical Unit _Los Angeles, California, United States
The safety of GCC-4401C when repeatedly administered to healthy male adults
The following safety parameters will be recorded at regular intervals during the clinical study\_ * Vital signs (supine blood pressure (BP) and pulse, oral body temperature, respiratory rate (RR)) * Twelve-lead ECG * 24-hour telemetry * Clinical laboratory testing (hematology, clinical chemistry, coagulation and urinalysis) * Hemoccult test * Adverse event assessments * Concomitant medication assessments * Physical examinations
Time frame: Up to 17 ~ 19 days after administration
The Pharmacokinetics (PK) of GCC-4401C when repeatedly administered to healthy male adults
The study consists of five cohorts (10 mg, 20 mg, 40 mg, 60 mg, and 80 mg) with eight subjects per cohort. In the 20 mg cohort, six additional subjects will receive rivaroxaban (Xarelto®) 20 mg as an active comparator in open-label fashion. Subjects will undergo dosing procedures on the morning of Day 1, and Day 3 to 9. * The following PK parameters for GCC-4401C and rivaroxaban will be determined after single dose, as appropriate\_ * Cmax * tmax * λz * Area under the curve from zero to the time of the last measurable concentration\[AUC(0-last)\] * Area under the curve from zero to infinity\[AUC(0-inf)\] * t½ * Apparent systemic clearance(CL/F) * Vz/F * The following parameters will be determined after repeat treatment for the GCC-4401C and rivaroxaban\_ * Trough plasma concentration(Ctrough) * Cmax,ss, * Cmin,ss, * tmax,ss, * λz,ss, * AUC(0 τ),ss, * t½,ss, * CL
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post dose on Day 1 and Day 9 and at pre dose on Days 5 through 8
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GCC-4401C matching placebo(Capsule): Strength is not applicable. GCC-4401C and placebo will be administered double-blind after a 10 hours fast.