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

November 29, 2011
September 23, 2014
November 2011
December 2014   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01483183 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Ascending Dose Study of OPC-108459 Intravenous Infusions in Patients With Paroxysmal and Persistent Atrial Fibrillation
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

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Atrial Fibrillation
  • Paroxysmal Atrial Fibrillation
  • Persistent Atrial Fibrillation
  • 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
  • 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.
    Intervention: Drug: OPC-108459
  • Placebo Comparator: Persistent or Paroxysmal AF Part 1: Placebo
    Intervention: Drug: Placebo
  • 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
    Intervention: Drug: OPC-108459
  • Placebo Comparator: Placebo Part 2
    Interventions:
    • Drug: OPC-108459
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
132
March 2015
December 2014   (final data collection date for primary outcome measure)

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
Both
18 Years to 85 Years
No
Contact: Study Information CADENCE215@mmgct.com
United States,   Denmark,   Germany,   Italy,   Netherlands,   Spain,   United Kingdom
 
NCT01483183
269-11-215
No
Otsuka Pharmaceutical Development & Commercialization, Inc.
Otsuka Pharmaceutical Development & Commercialization, Inc.
Not Provided
Not Provided
Otsuka Pharmaceutical Development & Commercialization, Inc.
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP