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Late Phase 2 Study of DU-176b in Patients With Non-Valvular Atrial Fibrillation

Primary Purpose

Atrial Fibrillation

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
DU-176b tablets
Warfarin potassium tablets
Sponsored by
Daiichi Sankyo Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Atrial Fibrillation focused on measuring Atrial fibrillation, Factor Xa inhibition

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with non-valvular atrial fibrillation who meet all of the following requirements will be considered for admission to the study:

    • Age≧20years
    • Atrial fibrillation confirmed by at least 2 electrocardiographic(ECG) tracings taken at an interval of ≧1week during the year before enrollment

  • Presence of any (at least )one of the following risk factors for embolism:

    • Hypertension
    • Diabetes mellitus
    • Congestive heart failure
    • Previous transient ischemic attack (TIA) or cerebral infarction (more than 30 days before giving informed consent )
    • Age≧75 years
    • At time of giving informed consent.
    • To be confirmed on ECG charts, etc.

Exclusion Criteria:

  • Presence of any of the following conditions with increased risk of hemorrhage:

    • History of intracranial, intraocular (excluding bleeding beneath the bulbar conjunctiva ), intrathecal, retroperitoneal, or non-traumatic intraarticular hemorrhage
    • History of gastrointestinal hemorrhage during the year before giving informed consent
    • History of peptic ulcers during the 90 days before giving informed consent
    • Surgical treatment or trauma requiring hospitalization during the 30 days before giving informed consent
    • Hemoglobin level <10 g/dL platelet count <10 ×10000 /μL at screening examinations
    • Active hemorrhage* present at giving informed consent or at enrollment
    • Any invasive therapeutic or diagnostic procedure (e.g., surgery, tissue, biopsy, and tooth extraction) scheduled during the period from the time of informed consent until completion of the trial treatment.
    • Any congenital hemorrhagic disease
  • History of cerebral infarction or TIA within 30 days before giving informed consent
  • Current treatment with any anticoagulant(other than warfarin)
  • Concurrent rheumatic valvular disease
  • History of valvular surgery
  • Concurrent infectious endocarditis
  • Concurrent cardiac myxoma
  • Confirmed left ventricular or left atrial thrombosis
  • Any congenital condition with a tendency toward thrombosis
  • Electrical or pharmacological defibrillation scheduled during the trial treatment
  • Uncontrolled hypertension (persistently high systolic ［>160mmHg］or diastolic [>100mmHg] pressure)
  • Uncontrolled diabetes mellitus

  • Renal or hepatic dysfunction (as defined below ), confirmed at screening examinations

    • Serum creatinine>1.5mg/dL
    • AST(GOT)or ALT(GPT)≧twice the upper limit of the reference range
    • Total bilirubin ≧twice the upper limit of the reference range
  • Current antiplatelet therapy for any concomitant illness that may be aggravated after discontinuation of the therapy.
  • Any concurrent severe cardiac disease
  • Known allergy to warfarin or any condition contraindicating its use
  • Inability to discontinue current treatment with vitamin K
  • Confirmed or potential pregnancy, wish to become pregnant during the study period, or current breast feeding
  • Previous treatment with DU-176b
  • Participation in a trial of any other drug during the 6 month before giving informed consent
  • Any other condition that disqualifies the patient for the study in the opinion of the investigator/subinvestigator *This includes ecchymosis identified as at least one hematoma sized ≧5 cm in longer diameter, macroscopic hematuria, and microscopic hematuria defined as a ≧2+test or a 1+ test for occult blood with a urine sediment containing ≧10 red cells per high-power field (except for a 2+ occult blood test persisting for 1 year before giving informed consent).

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

1

2

3

4

Arm Description

DU-176b low dose

DU-176b intermediate dose

DU-176b high dose

Warfarin

Outcomes

Primary Outcome Measures

Incidence of Bleeding Events (Major Bleeding, Clinically Relevant Non-major Bleeding and Minor Bleeding ) Identified During the Period From the Entry Into the Treatment Period Until Completion or Termination of the Treatment.
The primary endpoint was the incidence of bleeding events (major bleeding, clinically relevant non-major bleeding, or minor bleeding) that occurred during the treatment period.

Secondary Outcome Measures

Incidence of Thromboembolic Events (Cerebral Infarction and Systemic Embolism) Identified During the Period From the Entry to the Treatment Period Until Completion or Termination of the Treatment.
Incidence of Adverse Events and Adverse Reactions Identified During the Period From the Entry to the Treatment Period Until Completion or Termination of the Treatment
Pharmacodynamic Parameters (PT, PT-INR, and APTT)
PT - prothrombin time INR - International Normalized Ratio APTT - Activated Partial Thromboplastin time
Plasma DU-176 Concentration
Pharmacodynamic Biomarkers (F1+2, TAT, and D-dimer )

Full Information

First Posted
January 26, 2009
Last Updated
February 8, 2019
Sponsor
Daiichi Sankyo Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT00829933
Brief Title
Late Phase 2 Study of DU-176b in Patients With Non-Valvular Atrial Fibrillation
Official Title
A Randomized Dose-ranging Controlled Trial of DU-176b Versus Warfarin Potassium in Patients With Non-valvular Atrial Fibrillation
Study Type
Interventional

2. Study Status

Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
September 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo Co., Ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective of this study is to compare the incidence of hemorrhagic events in patients treated for non-valvular atrial fibrillation with DU-176b at each dose level versus warfarin potassium (warfarin). The secondary objective includes between-group comparisons with regard to incidence of thromboembolic events, pharmacodynamic parameters, and biomarkers for the efficacy evaluation, as well as incidence of adverse events and adverse reaction for the safety evaluation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation
Keywords
Atrial fibrillation, Factor Xa inhibition

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
536 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
DU-176b low dose
Arm Title
2
Arm Type
Experimental
Arm Description
DU-176b intermediate dose
Arm Title
3
Arm Type
Experimental
Arm Description
DU-176b high dose
Arm Title
4
Arm Type
Active Comparator
Arm Description
Warfarin
Intervention Type
Drug
Intervention Name(s)
DU-176b tablets
Intervention Description
DU-176b tablets taken once daily for up to 12 weeks
Intervention Type
Drug
Intervention Name(s)
Warfarin potassium tablets
Intervention Description
Warfarin potassium tablets taken once daily for up to 12 weeks
Primary Outcome Measure Information:
Title
Incidence of Bleeding Events (Major Bleeding, Clinically Relevant Non-major Bleeding and Minor Bleeding ) Identified During the Period From the Entry Into the Treatment Period Until Completion or Termination of the Treatment.
Description
The primary endpoint was the incidence of bleeding events (major bleeding, clinically relevant non-major bleeding, or minor bleeding) that occurred during the treatment period.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Incidence of Thromboembolic Events (Cerebral Infarction and Systemic Embolism) Identified During the Period From the Entry to the Treatment Period Until Completion or Termination of the Treatment.
Time Frame
12 weeks
Title
Incidence of Adverse Events and Adverse Reactions Identified During the Period From the Entry to the Treatment Period Until Completion or Termination of the Treatment
Time Frame
12 weeks
Title
Pharmacodynamic Parameters (PT, PT-INR, and APTT)
Description
PT - prothrombin time INR - International Normalized Ratio APTT - Activated Partial Thromboplastin time
Time Frame
12 weeks
Title
Plasma DU-176 Concentration
Time Frame
12 weeks
Title
Pharmacodynamic Biomarkers (F1+2, TAT, and D-dimer )
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with non-valvular atrial fibrillation who meet all of the following requirements will be considered for admission to the study: Age≧20years Atrial fibrillation confirmed by at least 2 electrocardiographic(ECG) tracings taken at an interval of ≧1week during the year before enrollment Presence of any (at least )one of the following risk factors for embolism: Hypertension Diabetes mellitus Congestive heart failure Previous transient ischemic attack (TIA) or cerebral infarction (more than 30 days before giving informed consent ) Age≧75 years At time of giving informed consent. To be confirmed on ECG charts, etc. Exclusion Criteria: Presence of any of the following conditions with increased risk of hemorrhage: History of intracranial, intraocular (excluding bleeding beneath the bulbar conjunctiva ), intrathecal, retroperitoneal, or non-traumatic intraarticular hemorrhage History of gastrointestinal hemorrhage during the year before giving informed consent History of peptic ulcers during the 90 days before giving informed consent Surgical treatment or trauma requiring hospitalization during the 30 days before giving informed consent Hemoglobin level <10 g/dL platelet count <10 ×10000 /μL at screening examinations Active hemorrhage* present at giving informed consent or at enrollment Any invasive therapeutic or diagnostic procedure (e.g., surgery, tissue, biopsy, and tooth extraction) scheduled during the period from the time of informed consent until completion of the trial treatment. Any congenital hemorrhagic disease History of cerebral infarction or TIA within 30 days before giving informed consent Current treatment with any anticoagulant(other than warfarin) Concurrent rheumatic valvular disease History of valvular surgery Concurrent infectious endocarditis Concurrent cardiac myxoma Confirmed left ventricular or left atrial thrombosis Any congenital condition with a tendency toward thrombosis Electrical or pharmacological defibrillation scheduled during the trial treatment Uncontrolled hypertension (persistently high systolic ［>160mmHg］or diastolic [>100mmHg] pressure) Uncontrolled diabetes mellitus Renal or hepatic dysfunction (as defined below ), confirmed at screening examinations Serum creatinine>1.5mg/dL AST(GOT)or ALT(GPT)≧twice the upper limit of the reference range Total bilirubin ≧twice the upper limit of the reference range Current antiplatelet therapy for any concomitant illness that may be aggravated after discontinuation of the therapy. Any concurrent severe cardiac disease Known allergy to warfarin or any condition contraindicating its use Inability to discontinue current treatment with vitamin K Confirmed or potential pregnancy, wish to become pregnant during the study period, or current breast feeding Previous treatment with DU-176b Participation in a trial of any other drug during the 6 month before giving informed consent Any other condition that disqualifies the patient for the study in the opinion of the investigator/subinvestigator *This includes ecchymosis identified as at least one hematoma sized ≧5 cm in longer diameter, macroscopic hematuria, and microscopic hematuria defined as a ≧2+test or a 1+ test for occult blood with a urine sediment containing ≧10 red cells per high-power field (except for a 2+ occult blood test persisting for 1 year before giving informed consent).
Facility Information:
City
Tokyo
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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/
IPD Sharing Time Frame
Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
IPD Sharing Access Criteria
Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
IPD Sharing URL
https://vivli.org/ourmember/daiichi-sankyo/

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Late Phase 2 Study of DU-176b in Patients With Non-Valvular Atrial Fibrillation

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