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Ascending Dose Study of OPC-108459 Intravenous Infusions in Patients With Paroxysmal and Persistent Atrial Fibrillation (CADENCE 215)

This study is currently recruiting participants.
Verified October 2012 by Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01483183
First received: November 29, 2011
Last updated: October 5, 2012
Last verified: October 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Paroxysmal Atrial Fibrillation
Persistent Atrial Fibrillation
 Drug: OPC-108459
Drug: Placebo
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-center, Parallel-group, Double-blind, Placebo-controlled, Randomized, Ascending Dose Trial to Determine the Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous Infusions of OPC-108459 Administered to Subjects With Paroxysmal and Persistent Atrial Fibrillation

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Part 1: Peak plasma concentration (Cmax) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Part 1: Area under the concentration-time curve (AUCt) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Part 1:QT interval corrected for heart rate using the Fridericia formula (QTcF) [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    QT= Uncorrected interval from onset of QRS complex to end of T wave. Measured using Holter monitor and local ECG readings.

  • Part 1: Ventricular rate [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
  • Part 1: Diastolic and systolic blood pressure [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
  • Part 2: Percent of subjects with normal sinus rhythm (NSR) [ Time Frame: 30 minutes ] [ Designated as safety issue: No ]
  • Part 2/1 infusion: Cmax [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Part 2/2 infusions: Cmax [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Part 2/1 infusion: AUCt [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Part 2/2 infusions: AUCt [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Part 2: QTcF [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
  • Part 2: Ventricular rate [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
  • Part 2: Diastolic and systolic blood pressure [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Part 1: Percentage of subjects with NSR [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Part 2: Time to NSR [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Part 2: Duration of NSR [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Part 2: Duration of NSR [ Time Frame: 168 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 132
Study Start Date: November 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Persistent or Paroxysmal AF Part 1: OPC-108459
To safely meet each of the following Cmax targets: 1.0-10.0 µg/mL. There will be 9 cohorts in all: 1.0, 1.6, 2.4, 3.6, 5.4, 7.0, 8.0, 9.0, and 10.0.
 Drug: OPC-108459

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

Other Names:
  • OPC-108459
  • OPC-269
Placebo Comparator: Persistent or Paroxysmal AF Part 1: Placebo Drug: Placebo
Placebo dose, 10-minute constant rate IV infusion
Experimental: Persistent or Paroxysmal AF Part 2: OPC-108459
Single dose to safely meet target concentration from Part 1, if subject fails to convert to sinus rhythm within 10 minutes, second dose will be administered to achieve 25% increase when compared to first infusion
 Drug: OPC-108459

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

Other Names:
  • OPC-108459
  • OPC-269
Placebo Comparator: Placebo Part 2 Drug: OPC-108459

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

Other Names:
  • OPC-108459
  • OPC-269
Drug: Placebo
Placebo dose, 10-minute constant rate IV infusion

Detailed Description:

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. Each cohort will be evaluated separately for all analysis parameters.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • History of pulmonary vein or atrial isolation, MAZE, mini-MAZE, or ablation
  • 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 screening
  • 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 6 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
  • History of AF who have failed electrical or pharmacological cardioversion

  • COPD requiring daily bronchodilation therapy

    • Subjects taking a moderate or strong CYP3A4 inhibitor less than 5 half-lives before screening
    • Subjects who have taken another investigational product within 30 days of dosing
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01483183

Contacts
Contact: Study Information CADENCE215@mmgct.com

  Show 24 Study Locations
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01483183     History of Changes
Other Study ID Numbers: 269-11-215
Study First Received: November 29, 2011
Last Updated: October 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Atrial fibrillation
Paroxysmal Atrial fibrillation
Persistent Atrial fibrillation
A-fib

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on May 16, 2013