A Study to Access Safety, Tolerability, Pharmacokinetics(PK) and Pharmacodynamics(PD) of Orally Administered GCC-4401C in Healthy Volunteers
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase I, Randomized, Double-blind, Placebo-controlled, Single and Multiple Sequential Ascending Dose Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered GCC-4401C in Healthy Males|
- The safety of GCC-4401C when repeatedly administered to healthy male adults [ Time Frame: Up to 17 ~ 19 days after administration ]
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
- The Pharmacokinetics (PK) of GCC-4401C when repeatedly administered to healthy male adults [ 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 ]
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_
- 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)]
- Apparent systemic clearance(CL/F)
The following parameters will be determined after repeat treatment for the GCC-4401C and rivaroxaban_
- Trough plasma concentration(Ctrough)
- AUC(0 τ),ss,
- The Pharmacodynamics (PD) of GCC-4401C when repeatedly administered to healthy male adults [ 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 ]
The following PD parameters for GCC-4401C and rivaroxaban will be determined, as appropriate_
- Activated partial thromboplastin time (aPTT)
- Prothrombin time (PT)
- International normalized ratio (INR)
- Coagulation Factor X assay
- Template bleeding time test
- Low Molecular Weight Heparin (Factor Xa inhibition test)
- Coagulation Factor X Chromogenic Activity Assay
|Study Start Date:||August 2013|
|Study Completion Date:||May 2014|
|Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Rivaroxaban
Orally active direct factor Xa inhibitor for use in the prevention and treatment of venous thromboembolic disease
Other Name: Nokxaban
Placebo Comparator: Placebo
GCC-4401C matching placebo capsule
Other Name: Nokxaban
Orally active direct factor Xa inhibitor for use in the prevention and treatment of venous thromboembolic disease. It is a novel molecule with a structural similarity to Rivaroxaban.
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.
Other Name: XareltoDrug: Placebo
GCC-4401C matching placebo(Capsule): Strength is not applicable. GCC-4401C and placebo will be administered double-blind after a 10 hours fast.
Other Name: GCC-4401C matching placebo
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01954238
|United States, California|
|Early phase clinical unit _Los Angeles, California, United States, CA 91206|
|Principal Investigator:||David Han, M.D.||California Clinical Trials Medical Group|