A Trial to Determine the Safety, Pharmacokinetics, and Efficacy of OPC-108459 Administered as a Single Intravenous Dose to Patients With Paroxysmal or Persistent Atrial Fibrillation (AF)
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Intervention: OPC-108459; Placebo
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 48.0
Sex: All
Minimum age: 20 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      To investigate the safety, pharmacokinetics, and efficacy following 30-minute continuous
      intravenous administration of OPC-108459 at 0.4, 0.8, 1.6, or 2.4 mg/kg or placebo to
      patients with paroxysmal or persistent atrial fibrillation
    

Eligibility criteria:

        Inclusion Criteria:

          -  Japanese

          -  Male or female age 20 to 85 years, inclusive (at the time of informed consent)

          -  Patients diagnosed with recent or new onset of paroxysmal AF (3 hours to 7 days since
             the onset) or persistent AF (8 to 30 days since the onset) at time of randomization
             (prior to Investigational Medicinal Product [IMP] administration). Review of the
             patient's medical records and the judgment of the investigator or sub-investigator
             must be documented in the source documents to establish the date and duration of the
             most recent onset of AF.

          -  Patients who are receiving treatment according to the "Guidelines for Pharmacotherapy
             of Atrial Fibrillation (JCS 2008)" at time of screening and predosing examinations or
             who have a low risk of thromboembolic potential specified as follows:

               -  AF lasting less than 48 hours, OR

               -  For AF lasting for 48 hours or longer:

                    -  Patients receiving warfarin therapy for whom at least 3 weeks have elapsed
                       since achieving an international normalized ratio (INR) of 2.0 to 3.0 (1.6
                       to 2.6 for patients age 70 years or older) or in whom no thrombus in the
                       atrial main body or appendage is observed by transesophageal
                       echocardiography (TEE) within 24 hours before IMP administration

                    -  Patients in whom no thrombus in the atrial main body or appendage is
                       observed by TEE within 24 hours before IMP administration if they have not
                       undergone antithrombotic therapy or if they have undergone antithrombotic
                       therapy (including a new oral antithrombotic drug) which does not meet the
                       above criterion

          -  Patients with systolic blood pressure (sBP) of 90 mmHg or higher and lower than 160
             mmHg and diastolic blood pressure (dBP) of lower than 100 mmHg at screening
             examinations

          -  Female patients who have been postmenopausal for at least 12 consecutive months, or
             male and female patients who agree, together with their partners, to practice birth
             control as specified until 3 months after the start of IMP administration or who are
             surgically sterile (ie, have undergone orchiectomy or hysterectomy, respectively)

        Exclusion Criteria:

          -  QRS interval of > 120 msec

          -  Patients with heart failure of New York Heart Association (NYHA) Class II to IV or
             with left ventricular ejection fraction (LVEF) of < 40%

          -  Patients who currently have or have a history of a long QT syndrome, torsade de
             pointes, or an uncorrected QT interval of > 450 msec

          -  History of ventricular tachycardia, ventricular fibrillation, or resuscitated cardiac
             arrest

          -  History of AF and failed electrical or pharmacological cardioversion

          -  Current diagnosis of atrial flutter

          -  Patients with bradycardia (< 50 beats per minute [bpm]) or sick sinus syndrome, unless
             controlled by a pacemaker, except for physiologically transient sinus bradycardia
             observed at rest or during sleep

          -  Patients with Wolff-Parkinson-White syndrome

          -  Patients with any congenital severe heart disease

          -  Patients with severe aortic or mitral stenosis (aortic-valve area, < 1 cm2), severe
             mitral regurgitation, aortic regurgitation, congenital atrial septal defect, moderate
             or severe pulmonary hypertension, or any other disease leading to AF confirmed by
             echocardiography within one year prior to screening examinations

          -  Patients diagnosed with congenital valvular anomaly or severe valve disease (eg,
             aortic or mitral stenosis, severe right or left ventricular systolic dysfunction, or
             severe pulmonary hypertension) and confirmed current presence of the condition by TEE
             at screening examinations

          -  Patients diagnosed with stroke or transient ischemic attack within one year prior to
             screening examinations or with carotid artery stenosis of 50%

          -  History of myocardial infarction within 6 months prior to screening examinations

          -  Findings of acute coronary syndrome, angina, or myocardial ischemia diagnosed by ECG
             or drug-induced or exercise stress testing within 6 months prior to screening
             examinations