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 - Full Text View

Purpose

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.

Condition	Intervention	Phase
Atrial Fibrillation Thromboembolism	Drug: Edoxaban (DU-176b) Drug: warfarin	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention
Official Title:	A Phase 2, Randomized, Parallel Group, Multi Center, Multi National Study for the Evaluation of Safety of Four Fixed Dose Regimens of DU-176b in Subjects With Non- Valvular Atrial Fibrillation

Resource links provided by NLM:

Genetics Home Reference related topics: familial atrial fibrillation

MedlinePlus related topics: Atrial Fibrillation Blood Thinners

Drug Information available for: Warfarin Warfarin sodium Edoxaban Edoxaban tosylate

Genetic and Rare Diseases Information Center resources: Familial Atrial Fibrillation

U.S. FDA Resources

Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:

Adjudicated Incidence of Bleeding Events [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Adjudicated Incidence of Bleeding Events during treatment period
Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
liver enzyme (ALT and/or AST) and/or bilirubin (TBL) abnormalities

Secondary Outcome Measures:

Incidence of Major Adverse Cardiac Events MACE) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Mean (SD) change from baseline in D-dimer
Effects on Biomarker Prothrombin Fragments [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Median (min, max) values of Cmin,ss; Cmax,ss
Pharmacokinetics (AUC) of DU-176b in Subjects Receiving DU-176b [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Median (min, max) values of AUCss
Effects on Pharmacodynamic Biomarker Anti-Factor Xa Activity in Subjects Receiving DU-176b [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
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 Pharmacodynamic Biomarker PT in Subjects Receiving DU-176b [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
Mean (SD) change from baseline in biomarker International Normalized Ratio (INR) on Day 28, 1-3 hours post dose.


Enrollment:	1146
Study Start Date:	June 2007
Study Completion Date:	June 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 DU-176b 30mg tablet once daily	Drug: Edoxaban (DU-176b) 30mg tablet once daily
Experimental: 2 DU-176b 60mg once daily	Drug: Edoxaban (DU-176b) 60mg tablet once daily
Experimental: 3 DU-176b 30mg b.i.d.	Drug: Edoxaban (DU-176b) 30mg tablet two times a day
Experimental: 4 DU-176b 60mg tablets two times a day	Drug: Edoxaban (DU-176b) 60mg tablet two times a day
Active Comparator: 5 warfarin tablets	Drug: warfarin warfarin tablets

Eligibility


Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00504556

Show 91 Study Locations

Sponsors and Collaborators

Daiichi Sankyo Inc.

More Information


Responsible Party:	Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:	NCT00504556 History of Changes
Other Study ID Numbers:	DU176b-PRT018
Study First Received:	July 18, 2007
Results First Received:	February 5, 2015
Last Updated:	March 12, 2015
Health Authority:	United States: Food and Drug Administration Belgium: Federal Agency for Medicinal Products and Health Products Belarus: Ministry of Health Bosnia: Central Ethics Committee, Ministarstvo Zdravstva (Ministry of Health) Canada: Health Canada Chile: Instituto de Salud Pública de Chile Latvia: State Agency of Medicines Mexico: Federal Commission for Protection Against Health Risks Moldova: Central Ethics Committee, Drug Agency of Ministry of Health Russia: Ethics Committee Slovakia: State Institute for Drug Control Ukraine: Ministry of Health. Central Ethics Committee

Keywords provided by Daiichi Sankyo Inc.:


Anti-coagulant Non-valvular Venous Thromboembolism	Prevention of Blood Clots Atrial Fibrillation Non-valvular atrial fibrillation

Additional relevant MeSH terms:


Atrial Fibrillation Thromboembolism Arrhythmias, Cardiac Heart Diseases Cardiovascular Diseases Pathologic Processes Embolism and Thrombosis Vascular Diseases Edoxaban	Warfarin Anticoagulants Factor Xa Inhibitors Antithrombins Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 28, 2016