CompletedNCT02047565Updated Feb 12, 2019

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

A Phase 1 interventional study of 60mg edoxaban and 180mg edoxaban in Bleeding, sponsored by Daiichi Sankyo. Completed at 1 site in United States. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-02-12.

Sponsored by Daiichi Sankyo · Phase 1, Interventional, and Supportive care

Phase: Phase 1
Study type: Interventional
Enrollment: 110
Allocation: Randomized
Ages: 18 Years to 45 Years
Sex: All

Study summary

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.

Conditions studied

Bleeding

Browse trials for

Hemorrhage 3,000

Keywords

punch biopsy

In context

Hemorrhage

3,000 studies on the registry are indexed under Hemorrhage; 474 are open to participants now.

This study's enrollment of 110 is close to the median of 100 across 1,985 interventional studies indexed under Hemorrhage.

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Lead sponsor

Daiichi Sankyo is the lead sponsor of 316 studies on the registry; 35 are open to participants now.

Of its 51 completed or terminated interventional studies of FDA-regulated products, 38 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 45 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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.

Study design

Phase: Phase 1
Primary purpose: Supportive care
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Double (Participant, Care provider)
Enrollment: 110 participants (actual)

Study arms

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

Interventions

Drug60mg edoxaban
Drug180mg edoxaban
Drug50 IU/kg Beriplex P/N
Drug25 IU/kg Beriplex P/N
Drug10 IU/kg Beriplex P/N

What researchers measure

Primary outcomes

Bleeding duration 60mg edoxaban
To assess the variability and effect size of bleeding duration (BD) following punch biopsy in healthy subjects administered 60 mg edoxaban
Time frame: Day 1
Bleeding volume 60mg edoxaban
To assess the variability and effect size of bleeding volume (BV) following punch biopsy in healthy subjects administered 60 mg edoxaban
Time frame: Day 1
Bleeding duration 180mg edoxaban
To assess the variability and effect size of bleeding duration (BD) following punch biopsy in healthy subjects administered 180 mg edoxaban
Time frame: Day 1
Bleeding volume 180mg edoxaban
To assess the variability and effect size of bleeding volume (BV) following punch biopsy in healthy subjects administered 180 mg edoxaban
Time frame: Day 1

Secondary outcomes

Prothrombin Time
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
Time frame: Day 1
International Normalized Ratio
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
Time frame: Day 1
Activated Partial Thromboplastin Time
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
Time frame: Day 1
Thrombin Generation Assay
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
Time frame: Day 1
procoagulant markers D dimer
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)
Time frame: Day 1
prothrombin fragment F1 + 2
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)
Time frame: Day 1
coagulation factor concentrations
To evaluate the effects of Beriplex P/N following 60 mg edoxaban on coagulation factor concentrations
Time frame: Day 1
cmax of edoxaban and its active metabolite, D21-2393
To evaluate single dose pharmacokinetics (PK) of edoxaban and its active metabolite, D21-2393
Time frame: Day 1
tmax of edoxaban and its active metabolite, D21-2393
To evaluate single dose pharmacokinetics (PK) of edoxaban and its active metabolite, D21-2393
Time frame: Day 1
AUC 0-24 of edoxaban and its active metabolite, D21-2393
To evaluate single dose pharmacokinetics (PK) of edoxaban and its active metabolite, D21-2393
Time frame: Day 1

Study locations

1 site

Quintiles
Overland Park, Kansas 66211, United States

References and documents

Publications

Zahir H, Brown KS, Vandell AG, Desai M, Maa JF, Dishy V, Lomeli B, Feussner A, Feng W, He L, Grosso MA, Lanz HJ, Antman EM. Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate. Circulation. 2015 Jan 6;131(1):82-90. doi: 10.1161/CIRCULATIONAHA.114.013445. Epub 2014 Nov 17. Erratum In: Circulation. 2015 Jan 6;131(1):e10. PubMed 25403645 ↗

Individual participant data

Plan to share: Yes — De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Supporting information: Study protocol, Sap, Csr

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 12, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02047565
Lead sponsor: Daiichi Sankyo
Responsible party: Sponsor
First posted: Jan 28, 2014
Start date: Oct 2013
Primary completion: May 2014
Completion: May 2014
Last update: Feb 12, 2019

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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