Ascending Dose Study of OPC-108459 Intravenous Infusions in Patients With Paroxysmal and Persistent Atrial Fibrillation
Condition: Atrial Fibrillation; Paroxysmal Atrial Fibrillation; Persistent Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Intervention: OPC-108459; Placebo
Intervention description: 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 dose, 10-minute constant rate IV infusion
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Atrial fibrillation; Paroxysmal Atrial fibrillation; Persistent Atrial fibrillation; A-fib

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.
    

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