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A Study to Access Safety, Tolerability, Pharmacokinetics(PK) and Pharmacodynamics(PD) of Orally Administered GCC-4401C in Healthy Volunteers

This study has been completed.
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
Green Cross Corporation
ClinicalTrials.gov Identifier:
NCT01954238
First received: September 23, 2013
Last updated: December 18, 2014
Last verified: December 2014
  Purpose
The purpose of this study is to evaluate the safety, tolerability and Pharmacokinetics/Pharmacodynamics of multiple doses of GCC-4401C in healthy male subjects.

Condition Intervention Phase
Healthy Volunteers
Drug: GCC-4401C
Drug: Rivaroxaban
Drug: Placebo
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Green Cross Corporation:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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_

      • 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)]
      • 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


Other Outcome Measures:
  • 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


Enrollment: 46
Study Start Date: August 2013
Study Completion Date: May 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rivaroxaban
Orally active direct factor Xa inhibitor for use in the prevention and treatment of venous thromboembolic disease
Drug: GCC-4401C
  • 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.
Other Name: Nokxaban
Placebo Comparator: Placebo
GCC-4401C matching placebo capsule
Drug: GCC-4401C
  • 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.
Other Name: Nokxaban
Experimental: GCC-4401C
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.
Drug: 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: Xarelto
Drug: 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

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Subject voluntarily has agreed to participate in this study and signed an Institutional Review Board (IRB)-approved informed consent before any of the Screening procedures will be performed.
  2. Males between 18 to 45 years of age, inclusive, at Screening.
  3. Non-smokers (or other nicotine use) as determined by history (no nicotine use over the past month prior to screening) and by urine cotinine concentration (< 400 ng/mL) at Screening.
  4. Body mass index (BMI) between 18.5 and 28.0 kg/m2 at Screening.
  5. Healthy, determined by pre-study medical evaluation and Investigator/designee discretion (medical history, physical examination, vital signs, ECG, and clinical laboratory evaluations).

Exclusion Criteria:

  1. Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s) as determined by the Investigator/designee.
  2. Any disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs.
  3. Have any of the following, which may put them at increased risk with anticoagulant use: family history or personal history of bleeding disorders or diseases/syndromes that can either alter or increase the propensity for bleeding; any other contraindication to anticoagulant treatment, or increased bleeding risk, as judged by the Investigator.
  4. Are considering or scheduled to undergo any surgical procedure during the study.
  5. Any concurrent disease or condition that, in the opinion of the Investigator/designee, would make the subject unsuitable for participation in the clinical study.
  6. Fecal occult blood positive test at screening and admission.
  7. Subject has history of alcohol and/or illicit drug abuse within one year of the Screening visit.
  8. Positive Screening test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody, or human immunodeficiency virus (HIV) antibody.
  9. Positive alcohol breathalyzer test at Screening or Day -1.
  10. Positive urine drug test (cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids, etc.) at Screening or Day -1.
  11. Subject unwilling to avoid consumption of coffee and caffeine containing beverages within 48 hours prior to Day -1 until discharge from the clinical site.
  12. Subject unwilling to avoid use of alcohol or alcohol-containing foods, medications or beverages, within 48 hours prior to Day -1 until discharge from the clinical site.
  13. Donation of blood (> 500 mL) or blood products within 2 months (56 days) prior to Day -1.
  14. Use of over-the-counter (OTC) medications, prescription medications, or herbal remedies from 14 days or 5 time their half-lives whatever is more, prior to Day -1 and vitamin from 7 days prior to Day -1, until End-of-Study. By exception, acetaminophen 1000 mg per day is permitted.
  15. Use of any drugs that induce or inhibit cytochrome P450 or P-glycoprotein within 30 days prior to dosing.
  16. Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of dosing.
  17. Use of an investigational drug within 30 days prior to Day 1.
  18. Unwilling to abstain from vigorous exercise from 48 hours prior to Day -1 until End-of-Study.
  19. Subject has a history of hypersensitivity to the investigational medicinal products (IMPs) or any of the excipients or to medicinal products with similar chemical structures.
  20. Planning to father a child or donate sperm during the study and within 3 months following dosing.
  21. Subject does not have veins suitable for cannulation or multiple venipunctures.
  22. Subject is unable to understand the protocol requirements, instructions and study related restrictions, the nature, scope and possible consequences of the clinical study.
  23. Subject is unlikely to comply with the protocol requirements, instructions and study related restrictions; e.g., uncooperative attitude, inability to return for Follow-up visits and improbability of completing the clinical study.
  24. Subject has previously been enrolled in this clinical study.
  25. Subjects involved in the planning or conduct of this clinical study.
  26. Vulnerable subject (e.g. kept in detention)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01954238

Locations
United States, California
PAREXEL Internatonal
Early phase clinical unit _Los Angeles, California, United States, CA 91206
Sponsors and Collaborators
Green Cross Corporation
Parexel
Investigators
Principal Investigator: David Han, M.D. California Clinical Trials Medical Group
  More Information

Responsible Party: Green Cross Corporation
ClinicalTrials.gov Identifier: NCT01954238     History of Changes
Other Study ID Numbers: GC2107_102 
Study First Received: September 23, 2013
Last Updated: December 18, 2014

Keywords provided by Green Cross Corporation:
Anti-coagulant
Coagulation factor Xa inhibitor

Additional relevant MeSH terms:
Rivaroxaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants

ClinicalTrials.gov processed this record on February 17, 2017