Status: Recruiting
Keywords: OPC-108459 , atrial fibrillation
IRB Number: 00058095
Specialty: Cardiology, Clinical Pharmacology, Pharmacotherapy
Sub Specialties:

Brief Summary

Part 1: To determine the safety, tolerability, pharmacokinetics, and efficacy of single ascending doses of OPC-108459 following one 10-minute constant rate infusion in adult subjects diagnosed with paroxysmal or persistent AF.

Part 2: To determine the efficacy and safety of OPC-108459 following up to two 10-minute constant rate infusions in adult subjects diagnosed with paroxysmal or persistent AF.

Principal Investigator: Nazem Akoum
Department: Cardiology
Co Investigator: Nassir Marrouche
Co Investigator: Ravi Ranjan
Co Investigator: Frederick Han

Contact Information

Name:Nereida Ortez
Phone: 801-585-1380

Inclusion Criteria

  1. Subject should be > 18 years and up to 85 years old
  2. Subjects with paroxysmal AF (recent or new onset) duration defined as 3 hours to £ 7 days (Group 1 only); or subjects with persistent AF duration > 7 days and up to 30 days (Group 2 only) at the time of randomization. REviw of subject medical records and the judgment of the Principal Investigatro should be documented to establish the date of onset and duration of AF.
  3. Either the subject or their legally acceptable representative should provide an informed consent.
  4. Subject should be hemodynamically stable defined as a screening systolic blood pressure between 90 to 160 mmHg, diastolic < 100 mmHg.
  5. Subjects with low risk of thromboembolic potential as documented by
    1. Subjects with AF lasting < 48 hours (by ECG)
    2. Subjects with AF duration longer than 48 hours, have had 3-weeks of anti-coagulation therapy and an International Normalized Ratio (INR) of 2.0 – 3.0 prior to dosing or a transesophageal echocardiogram (TEE) to establish the absence of atrial main body or appendage thrombus within 24 hours prior to dosing. Adequate anticoagulation with warfarin (requires INR monitoring), dabigatran, or a factor Xa inhibitor based on regional guidelines needs to be in place at the time of drug infusion.
    3. Subjects managed in accordance with ACC/AHA/ESC anticoagulation guidelines or in accordance with more recently-approved compounds as approved for this indication by the FDA.  Pre-screening treatment with beta-adrenergic blocking agents, calcium antagonists and digoxin for control of ventricular rate is permitted.
  6. Male and female subjects who are surgically sterile (i.e., have undergone orchidectomy or hysterectomy, respectively); female subjects who have been postmenopausal for a t least 12 consecutive months; male and female subjects who agree to remain abstinent or to practice double-barrier forms of birth control from trial screening through 30 days from the last dose of IMP.  Double barrier forms of birth control include use of two of the following precautions: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device (IUD), birth control pill, birth control implant, or birth control depot injections combined with either condom, or sponge with spermicide.

Exclusion Criteria

  1. History of long QT syndrome, Torsade de Pointes or an uncorrected QT interval of > 450 ms.
  2. QRS interval > 120 ms at Screening.
  3. History of myocardial infarction within 6 months of screening.
  4. Symptoms of acute coronary syndrome, angina or active myocardial ischemia diagnosed by ECG, or imaging stress testing within 6 months of screening.
  5. History of ventricular tachycardia, fibrillation, or resuscitated cardiac arrest.
  6. History of clinically significant congenital heart disease.
  7. Presence of severe aortic or mitral stenosis (valve area < 1.0 cm-sq), aortic or mitral regurgitation, (greater than moderate severity). Atrial septal defect, greater than mild pulmonary hypertension, or other conditions leading to AF with echo confirmation of this within the 12 months prior to Screening
  8. History of pulmonary vein or atrial isolation, MAZE, or mini-MAZE procedures or atrial-ventricular nodal ablation.
  9. Part 1: Any subject with a diagnosis of heart failure NYHA Class II – IV or with an ejection fraction < 40%.  Part 2: Subjects with a diagnosis of heart failure NYHA Class IV or NYHA I, II or III with an ejection fraction < 35% as determined by any imaging method within 6 months of Screening
  10. Subjects that have received concomitant treatment with class I or III anti-arrhythmic agents or unless the medication was discontinued more than 5 half-lives before dosing.
  11. History of seizures.
  12. Current diagnosis of atrial flutter.
  13. Diagnosis of stroke, TIA (transient ischemic attack), or any transient neurological deficit within 1 year of screening or known carotid artery stenosis of > 50%/
  14. Cardiac surgery within 6 months of screening.
  15. Bradycardia (<50 bpm) of sick sinus syndrome, unless controlled by a pacemaker. 
  16. Current reversible cause of AF such as hyperthyroidism, pulmonary embolism, alcohol intoxication, pericarditis.
  17. Wolff-Parkinson-White syndrome.
  18. Subject diagnosed with any congenital abnormality, severe valve disease, E.g., aortic or mitral stenosis, severe right or left systolic dysfunction or severe pulmonary hypertension.  This can be confirmed by TEE during screening.
  19. Subjects with history of AF who have failed electrical or pharmacological cardioversion.
  20. COPD requiring daily bronchodilation therapy.
  21. [Removed with sponsor amendment 3]
  22. The following laboratory results at screening: serum potassium < 3.5 mEq/L, magnesium < 1.5 mEq/L, serum creatinine ³ 1.8 g/dL. Hemoglobin < 9 g/dL in women or < 11 g/dL in men and liver enzymes 1.5 ULN.
  23. Administration of another investigational product within 30 days of dosing.
  24. Any medical condition, in the opinion of the investigator, which could interfere with evaluation of the trial objectives or safety of the subjects (e.g., anti-arrhythmic agents, previous cardiac ablation or cardioversion).