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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 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: September 23, 2014
Last verified: September 2014
  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 ]

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
  • 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 Names:
  • OPC-108459
  • 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 Names:
  • OPC-108459
  • 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. 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 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 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 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

Contacts
Contact: Study Information CADENCE215@mmgct.com

  Show 31 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: September 23, 2014
Health Authority: United States: Food and Drug Administration
Denmark: Danish Health and Medicines Authority
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 30, 2014