Venous ThromboembolismPhase 3NCT01857583

Safety and Pharmacokinetics Study of DU-176b Administered to Patients With Severe Renal Impairment Undergoing Orthopedic Surgery of The Lower Limbs

A Phase 3 study testing 15mg DU-176b, 30mg DU-176b and Fondaparinux in people with Venous Thromboembolism, run by Daiichi Sankyo Co., Ltd. at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To assess the safety and pharmacokinetics of DU-176b administered to patients with severe renal impairment undergoing orthopedic surgery of the lower limbs, compared with DU-176b administered to patients with mild renal impairment (MiRI) undergoing orthopedic surgery of the lower limbs. Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Venous Thromboembolism
What is being tested?: 15mg DU-176b, 30mg DU-176b and Fondaparinux
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 80 participants
Where: 1 siteJapan
Study dates: Mar 2012to Dec 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients with SRI or MiRI undergoing orthopedic surgery of the lower limbs

Who cannot join

Patients who are on hemodialysis or are scheduled to undergo hemodialysis during the study period
Patients who are at a significantly high risk for bleeding or thromboembolism
Patients who are receiving another antithrombotic therapy and are unable to suspend the therapy
Patients who have evidence of hepatic function test abnormalities

Trial locations and contacts

1 site in 1 country.

Japan1 site

Toyooka Chuo Hospital
Asahikawa, Hokkaido Prefecture, 078-8237

Other trials in Japan

About this study

Official title: Phase III Clinical Study of DU-176b (Venous Thromboembolism): Japanese, Multicenter, Open-label Study of DU-176b in Patients With Severe Renal Impairment (SRI) Undergoing Orthopedic Surgery of the Lower Limbs

For reference, the safety of DU-176b in patients with SRI undergoing orthopedic surgery of the lower limbs will be compared with that of fondaparinux.

Conditions: Venous Thromboembolism
Being tested: 15mg DU-176b, 30mg DU-176b, Fondaparinux
Keywords: anticoagulant, DU-176b, edoxaban, factor Xa, oral, orthopedic surgery of lower limbs, severe renal impairment
Medical subject headings: Venous Thromboembolism, Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

15mg DU-176bDrug
Also called edoxaban
30mg DU-176bDrug
Also called edoxaban
FondaparinuxDrug

Study groups in NCT01857583
Study group	Role	What they receive
SRI 15mg (15 mL/min ≤ CLCR < 20mL/min)	Experimental	Severe Renal Impairment group orally administered 15mg DU-176b once daily for 14 days. Receives: Drug: 15mg DU-176b
MiRI 30mg (50 mL/min ≤ CLCR ≤ 80mL/min)	Experimental	Mild Renal Impairment group orally administered 30mg DU-176b once daily for 14 days. Receives: Drug: 30mg DU-176b
Fondaparinux (20 mL/min ≤ CLCR < 30mL/min)	Active comparator	Fondaparinux subcutaneously administered at a dose of 1.5mg once daily for 14 days. Receives: Drug: Fondaparinux
SRI 15mg (20 mL/min ≤ CLCR < 30mL/min)	Experimental	Severe Renal Impairment group orally administered 15mg DU-176b once daily for 14 days. Receives: Drug: 15mg DU-176b

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of Any Adjudicated Bleeding Events
Incidence of any adjudicated bleeding events (including major bleeding, clinically relevant non-major bleeding, and minor bleeding).
Measured: 14 days
Incidence of Adverse Events
Measured: 1 month
Incidence of Adverse Drug Reactions
Measured: 1 month
Plasma Concentration of DU-176b
Measured: 14 days
Plasma Concentration of D21-2393
Measured: 14 days

Secondary outcomes (1)

Incidence of Adjudicated Thromboembolic Events
Incidence of adjudicated thromboembolic events (symptomatic Deep Vein Thrombosis (DVT), symptomatic Pulmonary Thromboembolism (PTE), Venous Thromboembolism (VTE) related deaths).
Measured: 1 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2012Dec 2012

First posted20 May 2013 (estimated)
Study startMar 2012
Primary completionDec 2012
Study completionDec 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
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 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 80 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01857583
Sponsor's protocol ID: DU176b-B-J306
Status last verified: Feb 2015
First submitted: 16 May 2013
Last updated: 5 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
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

Fuji T, Fujita S, Kawai Y, Abe Y, Kimura T, Fukuzawa M, Abe K, Tachibana S. A randomized, open-label trial of edoxaban in Japanese patients with severe renal impairment undergoing lower-limb orthopedic surgery. Thromb J. 2015 Jan 30;13(1):6. doi: 10.1186/s12959-014-0034-9. eCollection 2015.
PubMed 25653574

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Venous Thromboembolism trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase III Clinical Study of DU-176b (Venous Thromboembolism): Japanese, Multicenter, Open-label Study of DU-176b in Patients With Severe Renal Impairment (SRI) Undergoing Orthopedic Surgery of the Lower Limbs
ClinicalTrials.gov ID: NCT01857583
Acronym / sponsor ID: DU176b-B-J306
Conditions: Venous Thromboembolism
Keywords: anticoagulant, DU-176b, edoxaban, factor Xa, oral, orthopedic surgery of lower limbs, severe renal impairment
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 80 participants (actual)
Lead sponsor: Daiichi Sankyo Co., Ltd.Industry (pharma, biotech, devices)
Study start: Mar 2012
Primary completion: Dec 2012 (actual)
Study completion: Dec 2012 (actual)
First posted: 20 May 2013 (estimated)
Results: Posted 26 Jan 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

For reference, the safety of DU-176b in patients with SRI undergoing orthopedic surgery of the lower limbs will be compared with that of fondaparinux.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
SRI 15mg (15 mL/min ≤ CLCR < 20mL/min)	Experimental	Drug: 15mg DU-176bSevere Renal Impairment group orally administered 15mg DU-176b once daily for 14 days.
MiRI 30mg (50 mL/min ≤ CLCR ≤ 80mL/min)	Experimental	Drug: 30mg DU-176bMild Renal Impairment group orally administered 30mg DU-176b once daily for 14 days.
Fondaparinux (20 mL/min ≤ CLCR < 30mL/min)	Active comparator	Drug: FondaparinuxFondaparinux subcutaneously administered at a dose of 1.5mg once daily for 14 days.
SRI 15mg (20 mL/min ≤ CLCR < 30mL/min)	Experimental	Drug: 15mg DU-176bSevere Renal Impairment group orally administered 15mg DU-176b once daily for 14 days.

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Patients with SRI or MiRI undergoing orthopedic surgery of the lower limbs

Key exclusion criteria (4 listed)

Patients who are on hemodialysis or are scheduled to undergo hemodialysis during the study period
Patients who are at a significantly high risk for bleeding or thromboembolism
Patients who are receiving another antithrombotic therapy and are unable to suspend the therapy
Patients who have evidence of hepatic function test abnormalities

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
15mg DU-176bAlso: edoxaban	Drug	SRI 15mg (15 mL/min ≤ CLCR < 20mL/min), SRI 15mg (20 mL/min ≤ CLCR < 30mL/min)
30mg DU-176bAlso: edoxaban	Drug	MiRI 30mg (50 mL/min ≤ CLCR ≤ 80mL/min)
Fondaparinux	Drug	Fondaparinux (20 mL/min ≤ CLCR < 30mL/min)

Primary outcome

Incidence of Any Adjudicated Bleeding Events
Time frame: 14 days
Incidence of any adjudicated bleeding events (including major bleeding, clinically relevant non-major bleeding, and minor bleeding).
Incidence of Adverse Events
Time frame: 1 month
Incidence of Adverse Drug Reactions
Time frame: 1 month
Plasma Concentration of DU-176b
Time frame: 14 days
Plasma Concentration of D21-2393
Time frame: 14 days

1 secondary outcome

Incidence of Adjudicated Thromboembolic Events
Time frame: 1 month

Results and safety

Results posted to the registry on 26 Jan 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MiRI 30mg DU176b (50 mL/Min ≤ CLCR ≤ 80mL/Min)	30	29
SRI 15mg DU176b (15 mL/Min ≤ CLCR < 20 mL/Min)	7	6
SRI 15mg DU176b (20 mL/Min ≤ CLCR < 30 mL/Min)	22	19
Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min)	21	17

Primary outcome: Incidence of Any Adjudicated Bleeding Events

Time frame: 14 days. Number (95% Confidence Interval). Unit: percentage of subjects with bleeds

Measure	MiRI 30mg DU 176b (50 mL/Min ≤ CLCR ≤ 80 mL/Min) n = 30	SRI 15mg DU 176b (15 mL/Min ≤ CLCR < 20 mL/Min) n = 7	SRI 15mg DU 176b (20 mL/Min ≤ CLCR < 30 mL/Min) n = 22	Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min) n = 20
Value	33.3 (19.2 to 51.2)	14.3 (2.6 to 51.3)	22.7 (10.1 to 43.4)	40.0 (21.9 to 61.3)

MiRI 30mg DU 176b (50 mL/Min ≤ CLCR ≤ 80 mL/Min) vs SRI 15mg DU 176b (15 mL/Min ≤ CLCR < 20 mL/Min) vs SRI 15mg DU 176b (20 mL/Min ≤ CLCR < 30 mL/Min): Cox Proportional Hazard: 12.6 (95% CI -10.0 to 33.6), ANCOVA
SRI 15mg DU 176b (20 mL/Min ≤ CLCR < 30 mL/Min) vs Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min): Cox Proportional Hazard: 17.3 (95% CI -10.2 to 42.1), ANCOVA

Population analysed: The safety analysis set was defined as all subjects who were enrolled in the study, except for those who had significant GCP violations, who had not received the study drug, or who had no safety data after the start of study treatment.

Primary outcome: Incidence of Adverse Events

Time frame: 1 month

The sponsor has not posted figures for this outcome.

Primary outcome: Incidence of Adverse Drug Reactions

Time frame: 1 month

The sponsor has not posted figures for this outcome.

Primary outcome: Plasma Concentration of DU-176b

Time frame: 14 days

The sponsor has not posted figures for this outcome.

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MiRI 30mg DU 176b (50 mL/Min ≤ CLCR ≤ 80 mL/Min)	1 of 30 (3.3%)	22 of 30 (73.3%)	Not reported
SRI 15mg DU 176b (15 mL/Min ≤ CLCR < 20 mL/Min)	3 of 7 (42.9%)	6 of 7 (85.7%)	Not reported
SRI 15mg DU 176b (20 mL/Min ≤ CLCR < 30 mL/Min)	2 of 22 (9.1%)	12 of 22 (54.5%)	Not reported
Fondaparinux (20 mL/Min ≤ CLCR < 30mL/Min)	3 of 20 (15%)	12 of 20 (60%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 25653574Fuji T, Fujita S, Kawai Y, Abe Y, Kimura T, Fukuzawa M, Abe K, Tachibana S. A randomized, open-label trial of edoxaban in Japanese patients with severe renal impairment undergoing lower-limb orthopedic surgery. Thromb J. 2015 Jan 30;13(1):6. doi: 10.1186/s12959-014-0034-9. eCollection 2015.
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.

Takeshi Fuji, VP principal investigator

Osaka Koseinenkin Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 15mg DU-176b, 30mg DU-176b and Fondaparinux in people with Venous Thromboembolism, run by Daiichi Sankyo Co., Ltd. at 1 site in Japan.

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 4 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 5 Mar 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 Japan. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Incidence of Any Adjudicated Bleeding Events (time frame: 14 days). The study lists 5 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 NCT01857583, 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 5 Mar 2019.