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

This study has been terminated.
(Enrollment Difficulty)
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01483183
First received: November 29, 2011
Last updated: December 11, 2015
Last verified: December 2015
  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:


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 ]

Enrollment: 40
Study Start Date: November 2011
Study Completion Date: October 2015
Primary Completion Date: October 2015 (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 Name: 269-11-215
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 Name: 269-11-215
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 Name: 269-11-215
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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01483183

Locations
United States, District of Columbia
Otsuka Investigational Site
Washington, District of Columbia, United States, 20422
United States, Florida
Otsuka Investigational Site
Hollywood, Florida, United States, 33021
Otsuka Investigational Site
Jacksonville, Florida, United States, 32209
Otsuka Investigational Site
Sarasota, Florida, United States, 34232
United States, Kentucky
Otsuka Investigational Site
Lexington, Kentucky, United States, 40536
United States, Louisiana
Otsuka Investigational Site
New Orleans, Louisiana, United States, 70112
United States, New York
Otsuka Investigational Site
Johnson City, New York, United States, 13790
United States, Tennessee
Otsuka Investigational Site
Germantown, Tennessee, United States, 38138
United States, Texas
Otsuka Investigational Site
Houston, Texas, United States, 77024
Germany
Otsuka Investigational Site
Berlin, Germany, 13953
Otsuka Investigational Site
Hamburg, Germany, 22291
Otsuka Investigational Site
Leipzig, Germany, 04289
Otsuka Investigational Site
Pirna, Germany, 01796
Italy
Otsuka Investigational Site
San Fermo, Como, Italy, 22100
Otsuka Investigational Site
Ancona, Italy, 60126
Otsuka Investigational Site
Bologna, Italy, 40138
Otsuka Investigational Site
Cremona, Italy, 26100
Netherlands
Otsuka Investigational Site
Amsterdam, Netherlands, 1105AZ
Otsuka Investigational Site
Groningen, Netherlands, 9713GZ
Spain
Otsuka Investigational Site
Fuenlabrada, Madrid, Spain, 28942
Otsuka Investigational Site
Barcelona, Spain, 08970
Otsuka Investigational Site
Granada, Spain, 18014
Otsuka Investigational Site
Madrid, Spain, 28034
Otsuka Investigational Site
Madrid, Spain, 28905
United Kingdom
Otsuka Investigational Site
Chertsey, Surrey, United Kingdom, KT160PZ
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

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: December 11, 2015
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Italy: National Institute of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

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 September 26, 2016