BleedingPhase 1NCT02047565
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 study testing 60mg edoxaban, 180mg edoxaban and 50 IU/kg Beriplex P/N in people with Bleeding, run by Daiichi Sankyo at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Bleeding
- What is being tested?
- 60mg edoxaban, 180mg edoxaban and 50 IU/kg Beriplex P/N
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to May 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy subjects between 18 and 45 years of age, with a body mass index between 18 and 30 kg/m2, and weighing ≤ 110 kg.
Who cannot join
- 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.
Show all 21Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
- Bleeding
- Being tested
- 60mg edoxaban, 180mg edoxaban, 50 IU/kg Beriplex P/N, 25 IU/kg Beriplex P/N, 10 IU/kg Beriplex P/N
- Keywords
- punch biopsy
- Medical subject headings
- Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
60mg edoxabanDrug
180mg edoxabanDrug
50 IU/kg Beriplex P/NDrug
25 IU/kg Beriplex P/NDrug
10 IU/kg Beriplex P/NDrug
| Study group | Role | What they receive |
|---|---|---|
| Part 1 - 60mg edoxaban | Experimental | Treatment A: single oral dose of 60 mg edoxaban (1 × 60 mg tablet) Receives: Drug: 60mg edoxaban |
| Part 1 - 180mg edoxaban | Experimental | Treatment B: single oral dose of 180 mg edoxaban (3 × 60 mg tablet) Receives: Drug: 180mg edoxaban |
| Part 2 - 60mg edoxaban and 50 IU/kg Beriplex P/N | Experimental | 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 Receives: Drug: 60mg edoxaban; Drug: 50 IU/kg Beriplex P/N |
| Part 2 - 60mg edoxaban and 20 IU/kg Beriplex P/N | Experimental | 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 Receives: Drug: 60mg edoxaban; Drug: 25 IU/kg Beriplex P/N |
| Part 2 - 60mg edoxaban and 10 IU/kg Beriplex P/N | Experimental | 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 Receives: Drug: 60mg edoxaban; Drug: 10 IU/kg Beriplex P/N |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: Day 1
Secondary outcomes (10)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: Day 1
coagulation factor concentrations
To evaluate the effects of Beriplex P/N following 60 mg edoxaban on coagulation factor concentrations
Measured: 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
Measured: 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
Measured: 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
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2014 (estimated)
- Study startOct 2013
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for BleedingStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02047565
- Sponsor's protocol ID
- DU176b-A-U158
- Status last verified
- Jan 2015
- First submitted
- 2 Dec 2013
- Last updated
- 12 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- 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/
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.
PubMed 25403645
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02047565
- Acronym / sponsor ID
- DU176b-A-U158
- Conditions
- Bleeding
- Keywords
- punch biopsy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- Oct 2013
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 28 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part 1 - 60mg edoxaban | Experimental | Drug: 60mg edoxabanTreatment A: single oral dose of 60 mg edoxaban (1 × 60 mg tablet) |
| Part 1 - 180mg edoxaban | Experimental | Drug: 180mg edoxabanTreatment B: single oral dose of 180 mg edoxaban (3 × 60 mg tablet) |
| Part 2 - 60mg edoxaban and 50 IU/kg Beriplex P/N | Experimental | Drug: 60mg edoxaban, Drug: 50 IU/kg Beriplex P/NDose 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 |
| Part 2 - 60mg edoxaban and 20 IU/kg Beriplex P/N | Experimental | Drug: 60mg edoxaban, Drug: 25 IU/kg Beriplex P/NDose 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 |
| Part 2 - 60mg edoxaban and 10 IU/kg Beriplex P/N | Experimental | Drug: 60mg edoxaban, Drug: 10 IU/kg Beriplex P/NDose 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 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy subjects between 18 and 45 years of age, with a body mass index between 18 and 30 kg/m2, and weighing ≤ 110 kg.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 60mg edoxaban | Drug | Part 1 - 60mg edoxaban, Part 2 - 60mg edoxaban and 10 IU/kg Beriplex P/N, Part 2 - 60mg edoxaban and 20 IU/kg Beriplex P/N, Part 2 - 60mg edoxaban and 50 IU/kg Beriplex P/N |
| 180mg edoxaban | Drug | Part 1 - 180mg edoxaban |
| 50 IU/kg Beriplex P/N | Drug | Part 2 - 60mg edoxaban and 50 IU/kg Beriplex P/N |
| 25 IU/kg Beriplex P/N | Drug | Part 2 - 60mg edoxaban and 20 IU/kg Beriplex P/N |
| 10 IU/kg Beriplex P/N | Drug | Part 2 - 60mg edoxaban and 10 IU/kg Beriplex P/N |
Primary outcome
Bleeding duration 60mg edoxaban
Time frame: Day 1
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
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
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
To assess the variability and effect size of bleeding volume (BV) following punch biopsy in healthy subjects administered 180 mg edoxaban
10 secondary outcomes
Prothrombin Time
Time frame: Day 1
International Normalized Ratio
Time frame: Day 1
Activated Partial Thromboplastin Time
Time frame: Day 1
Thrombin Generation Assay
Time frame: Day 1
procoagulant markers D dimer
Time frame: Day 1
prothrombin fragment F1 + 2
Time frame: Day 1
coagulation factor concentrations
Time frame: Day 1
cmax of edoxaban and its active metabolite, D21-2393
Time frame: Day 1
tmax of edoxaban and its active metabolite, D21-2393
Time frame: Day 1
AUC 0-24 of edoxaban and its active metabolite, D21-2393
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2019.
- Derived from this study: PubMed 25403645Zahir 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.
- Individual participant dataSharing planned: 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/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 60mg edoxaban, 180mg edoxaban and 50 IU/kg Beriplex P/N in people with Bleeding, run by Daiichi Sankyo at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bleeding duration 60mg edoxaban (time frame: Day 1). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02047565, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2019.