Ascending Dose Study of OPC-108459 Intravenous Infusions in Patients With Paroxysmal and Persistent Atrial Fibrillation

NCT ID: NCT01483183

Last Updated: 2017-04-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2015-10-31

Brief Summary

The purpose of Part 1 of this study is to determine the maximally tolerated dose of OPC-108459 in patients with paroxysmal and persistent atrial fibrillation (AF).

The purpose of Part 2 of this study is to determine potential efficacy of dose(s) of OPC-108459 for the treatment of paroxysmal and persistent atrial fibrillation.

Detailed Description

This trial will test the pharmacokinetic and pharmacodynamic characteristics of ascending doses of OPC-108459 in separate populations of paroxysmal and persistent AF subjects.

The trial will consist of two parts. Each part will evaluate two populations of subjects presenting for cardioversion in a hospital setting.

Cohorts of paroxysmal and persistent subjects may have their dose increased independently.

Conditions

Atrial Fibrillation; Paroxysmal Atrial Fibrillation; Persistent Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Persistent or Paroxysmal AF Part 1: OPC-108459

To safely meet each of the following Cmax targets: 1.0-10.0 µg/mL. There will be 9 cohorts in all: 1.0, 1.6, 2.4, 3.6, 5.4, 7.0, 8.0, 9.0, and 10.0.

Group Type: EXPERIMENTAL

OPC-108459

Intervention Type: DRUG

Part 1: single dose OPC-108459, 10-minute constant rate IV infusion to achieve specified Cmax target

Part 2: single dose OPC-108459, 10-minute constant rate IV infusion to achieve Cmax target concentration from Part 1; if failure to convert to sinus rhythm, second dose OPC-108459 administered, 10-minute constant rate IV infusion to achieve target concentration from Part 1

Persistent or Paroxysmal AF Part 1: Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo dose, 10-minute constant rate IV infusion

Persistent or Paroxysmal AF Part 2: OPC-108459

Single dose to safely meet target concentration from Part 1, if subject fails to convert to sinus rhythm within 10 minutes, second dose will be administered to achieve 25% increase when compared to first infusion

Group Type: EXPERIMENTAL

OPC-108459

Intervention Type: DRUG

Part 1: single dose OPC-108459, 10-minute constant rate IV infusion to achieve specified Cmax target

Part 2: single dose OPC-108459, 10-minute constant rate IV infusion to achieve Cmax target concentration from Part 1; if failure to convert to sinus rhythm, second dose OPC-108459 administered, 10-minute constant rate IV infusion to achieve target concentration from Part 1

Placebo Part 2

Group Type: PLACEBO_COMPARATOR

OPC-108459

Intervention Type: DRUG

Part 1: single dose OPC-108459, 10-minute constant rate IV infusion to achieve specified Cmax target

Part 2: single dose OPC-108459, 10-minute constant rate IV infusion to achieve Cmax target concentration from Part 1; if failure to convert to sinus rhythm, second dose OPC-108459 administered, 10-minute constant rate IV infusion to achieve target concentration from Part 1

Placebo

Intervention Type: DRUG

Placebo dose, 10-minute constant rate IV infusion

Interventions

OPC-108459

Part 1: single dose OPC-108459, 10-minute constant rate IV infusion to achieve specified Cmax target

Part 2: single dose OPC-108459, 10-minute constant rate IV infusion to achieve Cmax target concentration from Part 1; if failure to convert to sinus rhythm, second dose OPC-108459 administered, 10-minute constant rate IV infusion to achieve target concentration from Part 1

Intervention Type: DRUG

Placebo

Placebo dose, 10-minute constant rate IV infusion

Intervention Type: DRUG

Other Intervention Names

269-11-215

Eligibility Criteria

Inclusion Criteria

• Subjects with paroxysmal atrial fibrillation (AF) (recent or new onset) or subjects with persistent AF at the time of randomization
• Subjects who are hemodynamically stable
• Subjects with a low risk of thromboembolic potential
• Subjects who are willing to comply with the reproductive precautions

Exclusion Criteria

Subjects with:

• History of long QT syndrome, Torsade de Pointes or an uncorrected QT interval of > 450 ms
• History of myocardial infarction within 6 months of screening
• Acute coronary syndrome, angina or active myocardial ischemia diagnosed by ECG, or other imaging within 6 months of screening
• History of ventricular tachycardia, fibrillation, or resuscitated cardiac arrest
• History of clinically significant congenital heart disease
• Presence of severe aortic or mitral stenosis, aortic or mitral regurgitation, atrial septal defect, or other conditions leading to AF
• Diagnosis of heart failure NYHA Class II-IV or with an ejection fraction <40% (Part 1 only)
• Diagnosis of heart failure NYHA Class IV or NYHA I, II, or III with an ejection fraction <35% (Part 2 only)
• Concomitant treatment with class I or III anti-arrhythmics agents unless the medication was discontinued more than 5 half-lives before dosing
• History of seizures
• Diagnosis of atrial flutter
• Diagnosis of stroke, TIA (transient ischemic attack), or any transient neurological deficit within 1 year of screening or known carotid artery stenosis of >50%
• Cardiac surgery within 3 months of screening
• Bradycardia (< 50 bpm) or sick sinus syndrome, unless controlled by a pacemaker
• Current reversible cause of AF
• Wolff-Parkinson-White syndrome
• Any congenital abnormality, severe valve disease
• Subjects who have taken another investigational product within 30 days of dosing

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Otsuka Investigational Site

Washington D.C., District of Columbia, United States

Otsuka Investigational Site

Hollywood, Florida, United States

Otsuka Investigational Site

Jacksonville, Florida, United States

Otsuka Investigational Site

Sarasota, Florida, United States

Otsuka Investigational Site

Lexington, Kentucky, United States

Otsuka Investigational Site

New Orleans, Louisiana, United States

Otsuka Investigational Site

Johnson City, New York, United States

Otsuka Investigational Site

Germantown, Tennessee, United States

Otsuka Investigational Site

Houston, Texas, United States

Otsuka Investigational Site

Berlin, , Germany

Otsuka Investigational Site

Hamburg, , Germany

Otsuka Investigational Site

Leipzig, , Germany

Otsuka Investigational Site

Pirna, , Germany

Otsuka Investigational Site

San Fermo, Como, Italy

Otsuka Investigational Site

Ancona, , Italy

Otsuka Investigational Site

Bologna, , Italy

Otsuka Investigational Site

Cremona, , Italy

Otsuka Investigational Site

Amsterdam, , Netherlands

Otsuka Investigational Site

Groningen, , Netherlands

Otsuka Investigational Site

Fuenlabrada, Madrid, Spain

Otsuka Investigational Site

Barcelona, , Spain

Otsuka Investigational Site

Granada, , Spain

Otsuka Investigational Site

Madrid, , Spain

Otsuka Investigational Site

Madrid, , Spain

Otsuka Investigational Site

Chertsey, Surrey, United Kingdom

Countries

United States; Germany; Italy; Netherlands; Spain; United Kingdom

Other Identifiers

269-11-215

Identifier Type: -

Identifier Source: org_study_id