Ascending Dose Study of OPC-108459 Intravenous Infusions in Patients With Paroxysmal and Persistent Atrial Fibrillation (CADENCE 215)

Otsuka

Status and phase: Terminated; Phase 1

Conditions: Paroxysmal Atrial Fibrillation; Atrial Fibrillation; Persistent Atrial Fibrillation

Treatments: Drug: OPC-108459; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01483183

269-11-215

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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40 participants in 4 patient groups, including a placebo group

Persistent or Paroxysmal AF Part 1: OPC-108459

Experimental group

Description:

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.

Treatment:

Drug: OPC-108459

Persistent or Paroxysmal AF Part 1: Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

Persistent or Paroxysmal AF Part 2: OPC-108459

Experimental group

Description:

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

Treatment:

Drug: OPC-108459

Placebo Part 2

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: OPC-108459