A Study to Assess the Safety of a Potential New Drug in Comparison to the Standard Practice of Dosing With Warfarin for Non-valvular Atrial Fibrillation

Phase 2

Completed

• Conditions: Atrial Fibrillation; Thromboembolism
• Interventions: Drug: Edoxaban (DU-176b); Drug: warfarin

• Registration Number: NCT00504556
• Lead Sponsor: Daiichi Sankyo

Brief Summary

This study is to assess the safety of a potential new drug DU-176b for the prevention of stroke/systemic embolic event (SEE) in individuals with non-valvular atrial fibrillation (AF). The duration is 3 months of treatment and a 30 day follow-up visit.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-06
• Study First Submitted: 2007-07-18
• Study First Submitted QC: 2007-07-18
• Study First Posted: 2007-07-20
• Primary Completion: 2008-06
• Study Completion: 2008-06
• Disposition First Submitted: 2010-08-25
• Disposition First Submitted QC: 2010-08-25
• Disposition First Posted: 2010-08-27
• Results First Submitted: 2015-02-05
• Status Verified: 2015-03
• Results First Submitted QC: 2015-03-12
• Results First Posted: 2015-03-13
• Last Update Submitted: 2019-02-08
• Last Update Posted: 2019-02-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1146

Inclusion Criteria

1. Male or female, 18 to 80 years old.
2. Able to provide written informed consent.
3. Persistent non-valvular AF supported by abnormal electrocardiogram (ECG)
4. A congestive heart failure, hypertension, age ≥ 75 years, diabetes, and prior stroke (CHADS2) index score of at least 2

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Exclusion Criteria

1. Subjects with mitral valve disease or previous valvular heart surgery
2. Known contraindication to any anticoagulant including vitamin K antagonists such as warfarin
3. Known or suspected hereditary or acquired bleeding or coagulation disorder

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Edoxaban (DU-176b)	DU-176b 30mg tablet once daily
3	Edoxaban (DU-176b)	DU-176b 30mg b.i.d.
2	Edoxaban (DU-176b)	DU-176b 60mg once daily
4	Edoxaban (DU-176b)	DU-176b 60mg tablets two times a day
5	warfarin	warfarin tablets

Primary Outcome Measures

Name	Time	Method
Adjudicated Incidence of Bleeding Events	3 months	Adjudicated Incidence of Bleeding Events during treatment period
Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA)	3 months	liver enzyme (ALT and/or AST) and/or bilirubin (TBL) abnormalities

Secondary Outcome Measures

Name	Time	Method
Incidence of Major Adverse Cardiac Events MACE)	3 months	MACE is defined as the composite of stroke \[ischemic or hemorrhagic\], Systemic embolic event (SEE), Myocardial Infarction (MI), Cardiovascular (CV) death, and hospitalization for any cardiac condition
Effects on Biomarker D-dimer	3 months	Mean (SD) change from baseline in D-dimer
Pharmacokinetics (AUC) of DU-176b in Subjects Receiving DU-176b	3 months	Median (min, max) values of AUCss
Effects on Pharmacodynamic Biomarker Anti-Factor Xa Activity in Subjects Receiving DU-176b	Day 28	Mean (SD) change from baseline in biomarker anti-Factor Xa \[FXa\] activity on Day 28, 1-3 hours post dose.
Effects on Pharmacodynamic Biomarker (Endogenous FX Activity) in Subjects Receiving DU-176b	Day 28	Mean (SD) change from baseline in biomarker endogenous FX activity on Day 28, 1-3 hours post dose.
Effects on Pharmacodynamic Biomarker PICT Activity in Subjects Receiving DU-176b	Day 28	Mean (SD) change from baseline in biomarker prothrombinase induced clotting time \[PICT\] on Day 28, 1-3 hours post dose.; PICT was determined by PICT aasay which is a plasma based functional assay to determine the anticoagulant activity on FXa and FIIa inhibition.
Effects on Biomarker Prothrombin Fragments	3 months	Mean (SD) change from baseline in Prothrombin Fragments 1 and 2 (F1 and F2)
Pharmacokinetics (Cmin, Cmax) of DU-176b in Subjects Receiving DU-176b	3 months	Median (min, max) values of Cmin,ss; Cmax,ss
Effects on Pharmacodynamic Biomarker PT in Subjects Receiving DU-176b	Day 28	Mean (SD) change from baseline in biomarker prothrombin time (PT) on Day 28, 1-3 hours post dose.
Effects on Pharmacodynamic Biomarker INR in Subjects Receiving DU-176b	Day 28	Mean (SD) change from baseline in biomarker International Normalized Ratio (INR) on Day 28, 1-3 hours post dose.