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

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.

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