Trial record 4 of 8 for:    beriplex p/n

A Two-part Study in Edoxaban-treated Healthy Subjects to Establish a Punch Biopsy Bleeding Model and to Evaluate the Effect of a 4-factor Prothrombin Complex Concentrate on Anticoagulation

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Daiichi Sankyo Inc.
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT02047565
First received: December 2, 2013
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

This Phase 1 study consists of 2 parts. Part 1 will be an open-label, randomized, 2 treatment, 2-way crossover study. Part 2 will be a double-blind (Sponsor unblinded), randomized, placebo controlled, sequential descending prothrombin complex concentrate dose, 2 sequence, 2 period crossover study. In both parts of the study, the assessor of BD and BV will remain blinded. In Part 2 of the study, both the subject and the clinic staff involved in study conduct will be blinded (with the exception of the pharmacist or nurse who prepares the blinded individual treatments from open-label supplies). The study programmer and statistician will also be blinded to treatment assignment. The Sponsor will remain unblinded for both parts of the study.


Condition Intervention Phase
Bleeding
Drug: 60mg edoxaban
Drug: 180mg edoxaban
Drug: 50 IU/kg Beriplex P/N
Drug: 25 IU/kg Beriplex P/N
Drug: 10 IU/kg Beriplex P/N
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Supportive Care
Official Title: A Two-part Study in Edoxaban-treated Healthy Subjects to Establish a Punch Biopsy Bleeding Model and to Evaluate the Effect of a 4-factor Prothrombin Complex Concentrate on Anticoagulation

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • Bleeding duration 60mg edoxaban [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    To assess the variability and effect size of bleeding duration (BD) following punch biopsy in healthy subjects administered 60 mg edoxaban

  • Bleeding volume 60mg edoxaban [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    To assess the variability and effect size of bleeding volume (BV) following punch biopsy in healthy subjects administered 60 mg edoxaban

  • Bleeding duration 180mg edoxaban [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    To assess the variability and effect size of bleeding duration (BD) following punch biopsy in healthy subjects administered 180 mg edoxaban

  • Bleeding volume 180mg edoxaban [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    To assess the variability and effect size of bleeding volume (BV) following punch biopsy in healthy subjects administered 180 mg edoxaban


Secondary Outcome Measures:
  • Prothrombin Time [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    To evaluate the reversal of the effect of 60 mg edoxaban on Prothrombin Time (PT), International Normalized Ratio (INR), Activated Partial Thromboplastin Time (aPTT), and Thrombin Generation Assay (TGA) parameters by Beriplex P/N

  • International Normalized Ratio [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    To evaluate the reversal of the effect of 60 mg edoxaban on Prothrombin Time (PT), International Normalized Ratio (INR), Activated Partial Thromboplastin Time (aPTT), and Thrombin Generation Assay (TGA) parameters by Beriplex P/N

  • Activated Partial Thromboplastin Time [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    To evaluate the reversal of the effect of 60 mg edoxaban on Prothrombin Time (PT), International Normalized Ratio (INR), Activated Partial Thromboplastin Time (aPTT), and Thrombin Generation Assay (TGA) parameters by Beriplex P/N

  • Thrombin Generation Assay [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    To evaluate the reversal of the effect of 60 mg edoxaban on Prothrombin Time (PT), International Normalized Ratio (INR), Activated Partial Thromboplastin Time (aPTT), and Thrombin Generation Assay (TGA) parameters by Beriplex P/N

  • procoagulant markers D dimer [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    To evaluate the effects of Beriplex P/N following 60 mg edoxaban on the procoagulant markers D dimer and prothrombin fragment F1 + 2 (F1 + 2)

  • prothrombin fragment F1 + 2 [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    To evaluate the effects of Beriplex P/N following 60 mg edoxaban on the procoagulant markers D dimer and prothrombin fragment F1 + 2 (F1 + 2)

  • coagulation factor concentrations [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    To evaluate the effects of Beriplex P/N following 60 mg edoxaban on coagulation factor concentrations

  • cmax of edoxaban and its active metabolite, D21-2393 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    To evaluate single dose pharmacokinetics (PK) of edoxaban and its active metabolite, D21-2393

  • tmax of edoxaban and its active metabolite, D21-2393 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    To evaluate single dose pharmacokinetics (PK) of edoxaban and its active metabolite, D21-2393

  • AUC 0-24 of edoxaban and its active metabolite, D21-2393 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    To evaluate single dose pharmacokinetics (PK) of edoxaban and its active metabolite, D21-2393


Estimated Enrollment: 90
Study Start Date: October 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 - 60mg edoxaban
Treatment A: single oral dose of 60 mg edoxaban (1 × 60 mg tablet)
Drug: 60mg edoxaban
Experimental: Part 1 - 180mg edoxaban
Treatment B: single oral dose of 180 mg edoxaban (3 × 60 mg tablet)
Drug: 180mg edoxaban
Experimental: Part 2 - 60mg edoxaban and 50 IU/kg Beriplex P/N
Dose cohort 1: 60 mg edoxaban + 50 IU/kg Beriplex P/N in 1 period and placebo (0.9% Sodium Chloride Injection, USP), in the other period
Drug: 60mg edoxaban Drug: 50 IU/kg Beriplex P/N
Experimental: Part 2 - 60mg edoxaban and 20 IU/kg Beriplex P/N
Dose cohort 2: 60 mg edoxaban + 25 IU/kg Beriplex P/N in 1 period and placebo (0.9% Sodium Chloride Injection, USP), in the other period
Drug: 60mg edoxaban Drug: 25 IU/kg Beriplex P/N
Experimental: Part 2 - 60mg edoxaban and 10 IU/kg Beriplex P/N
Dose cohort 3: 60 mg edoxaban + 10 IU/kg Beriplex P/N in 1 period and placebo (0.9% Sodium Chloride Injection, USP), in the other period
Drug: 60mg edoxaban Drug: 10 IU/kg Beriplex P/N

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy subjects between 18 and 45 years of age, with a body mass index between 18 and 30 kg/m2, and weighing ≤ 110 kg.

Exclusion Criteria:

  • Women of childbearing potential without proper contraceptive measures and women who are pregnant or breastfeeding. Women of childbearing potential who participate in the study must agree to use proper contraceptive measures from screening through 13 weeks after the last dose of study drug.
  • Subjects with history of unexplained syncope. Subjects who have prior clearance of vasovagal events may be included.
  • Subjects who have used any drugs or substances known to be strong inhibitors or strong inducers of cytochrome P450 (CYP) 3A4/5 enzymes or P-glycoprotein within 28 days prior to the first dosing.
  • Subjects who have used any other nonprescription drugs (including herbal supplemental), except acetaminophen (up to 3 g/day) within 14 days prior to check-in.
  • Subjects with history of major bleeding, major trauma, or major surgical procedure of any type within 6 months of dosing.
  • Subjects with history of peptic ulcer, gastrointestinal bleeding (including hematemesis, melena, and rectal bleeding), or bleeding from hemorrhoids.
  • Subjects with history of minor bleeding episodes such as epistaxis, rectal bleeding (spots of blood on toilet paper), and gingival bleeding within 3 months before the first dose.
  • Subjects who have any family history, suspected or documented, of coagulopathy.
  • Subjects who have participated in a previous edoxaban study within 6 months prior to the first dose.
  • Subjects who used anticoagulants (eg, warfarin, low molecular weight heparin), antiplatelet agents (eg, clopidogrel), non-steroidal anti-inflammatory drugs, and/or acetylsalicylic acid 30 days prior to punch biopsy or who expect to use these during the study.
  • Subjects with hemoglobin levels below 12 g/dL (men) or 11 g/dL (women) at screening.
  • Subjects with creatinine clearance ≤ 80 mL/min (based on the Cockcroft-Gault equation).
  • Subjects who are considered inappropriate for the punch biopsy procedure based on inability to visualize surface blood vessels, and history or likelihood of forming keloid scars.
  • Subjects with known heparin-induced thrombocytopenia.
  • Subjects who have a platelet count, PT, or INR outside of the normal range at baseline.
  • Subjects with history or current evidence of clinically significant cardiac, hepatic, renal, pulmonary, endocrine, neurologic, infectious, gastrointestinal, hematologic, or oncologic disease as determined by screening history, physical examination, laboratory test results, or 12-lead electrocardiogram (ECG).

In addition, for Part 2:

  • Subjects who are deficient in Factor V Leiden mutation.
  • Subjects who are deficient in protein S, protein C, antithrombin, or factor II, or have prothrombin 20210A mutation.
  • Subjects with known anaphylactic or severe systemic reactions to Beriplex P/N or any components in Beriplex P/N including heparin; FII, FVII, FIX, and FX; proteins C and S; antithrombin III; and human albumin.
  • Subjects with current or history of disseminated intravascular coagulation.
  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: NCT02047565

Locations
United States, Kansas
Quintiles Recruiting
Overland Park, Kansas, United States, 66211
Contact: Quintiles Phase, 1    866-267-4479      
Sponsors and Collaborators
Daiichi Sankyo Inc.
  More Information

No publications provided

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT02047565     History of Changes
Other Study ID Numbers: DU176b-A-U158
Study First Received: December 2, 2013
Last Updated: January 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Daiichi Sankyo Inc.:
punch biopsy

Additional relevant MeSH terms:
Hemorrhage
Pathologic Processes

ClinicalTrials.gov processed this record on July 24, 2014