A Multicenter, Parallel-group-comparison, Double-blind, Placebo-controlled, Randomized Trial to Determine the Safety, Pharmacokinetics, and Efficacy of OPC-108459 Administered as a Single Intravenous Dose to Patients With Paroxysmal or Persistent Atrial Fibrillatio
- Conditions
- Paroxysmal or Persistent Atrial Fibrillation
- Registration Number
- JPRN-jRCT2080222398
- Lead Sponsor
- Otsuka Pharmaceutical Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Sex
- All
- Target Recruitment
- Not specified
1) Japanese
2) Male or female age 20 to 85 years, inclusive (at the time of informed consent)
3) 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 subinvestigator must be documented in the source documents to establish the date and duration of the most recent onset of AF.
4) 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
5) 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
6) 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)
7) Patients who are capable of understanding the explanation of the trial and of giving written consent to participate of their own free will.
1) Female patients who are pregnant or nursing, or who test positive in urine pregnancy test at either time of screening or predose examinations
2) Body mass index (BMI) of more than 32.0 kg/m2 at screening examinations
3) Patients with any of the following clinical laboratory test results at screening (measurements obtained at the trial site will be used):
* Hemoglobin: less than 9 g/dL for females or less than 11 g/dL for males
* Aspartate aminotransferase (glutamate oxaloacetate transaminase) (AST [GOT]) and alanine aminotransferase (glutamate pyruvate transaminase) (ALT [GPT]): more than 1.5 x upper limit of reference range of the trial site
* Serum creatinine: equal to or more than 1.8 mg/dL
* Serum potassium: less than 3.5 mEq/L
* Serum magnesium: less than 1.5 mEq/L (less than 1.8 mg/dL)
4) QRS interval of more than 120 msec
5) Patients with heart failure of New York Heart Association (NYHA) Class II to IV or with left ventricular ejection fraction (LVEF) of less than 40%
6) Patients who currently have or have a history of a long QT syndrome, Torsade de Pointes, or an uncorrected QT interval of more than 450 msec
7) Patients who currently have or have a history of hypersensitivity to any drug (including all prescription drugs and over-the-counter medical products)
8) Patients who currently have or have a history of alcohol dependence, drug dependence, or drug abuse
9) Patients showing symptoms of urinary retention or dysuria resulting from prostatic hyperplasia
10) History of seizures or syncope
11) History of ventricular tachycardia, ventricular fibrillation, or resuscitated cardiac arrest
12) History of AF and failed electrical or pharmacological cardioversion
13) Current diagnosis of atrial flutter (sawtooth wave of duration equal to or longer than the time required for standard electrocardiography [ECG] [several tens of seconds]). However, patients with a waveform similar to atrial flutter but with an unstable sawtooth wave that reverts to an AF waveform within several seconds (so-called atrial flutter/fibrillation) will not be excluded if the waveform is observed at the screening period, but will be excluded if the waveform is observed on the day of IMP administration.
14) Patients with bradycardia (less than 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
15) Patients with a reversible cause of AF, such as hyperthyroidism, pulmonary embolism, alcohol intoxication, or acute pericarditis
16) Patients with Wolff-Parkinson-White syndrome
17) Patients with glaucoma
18) Patients with any congenital severe heart disease
19) Patients with severe aortic or mitral stenosis (aortic-valve area, less than 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
20) 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
21) Patients diagnosed with stroke or transient ischemic attack within one year prior to screening examinations or with carotid artery stenosis of equal to or more than 50%
22) Histo
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method