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

Atrial Fibrillation Clinical Trial

— CADENCE 215  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01483183
• Other study ID #: 269-11-215
• Status: Terminated
• Phase: Phase 1
• First received: November 29, 2011
• Last updated: December 11, 2015
• Start date: November 2011
• Est. completion date: October 2015

Study information

• Verified date: December 2015
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesItaly: The Italian Medicines AgencyItaly: National Institute of HealthNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Spain: Agencia Española de Medicamentos y Productos SanitariosUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Paroxysmal Atrial Fibrillation
• Persistent Atrial Fibrillation

Intervention

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
• Placebo
Placebo dose, 10-minute constant rate IV infusion

Locations

Country	Name	City	State
Germany	Otsuka Investigational Site	Berlin
Germany	Otsuka Investigational Site	Hamburg
Germany	Otsuka Investigational Site	Leipzig
Germany	Otsuka Investigational Site	Pirna
Italy	Otsuka Investigational Site	Ancona
Italy	Otsuka Investigational Site	Bologna
Italy	Otsuka Investigational Site	Cremona
Italy	Otsuka Investigational Site	San Fermo	Como
Netherlands	Otsuka Investigational Site	Amsterdam
Netherlands	Otsuka Investigational Site	Groningen
Spain	Otsuka Investigational Site	Barcelona
Spain	Otsuka Investigational Site	Fuenlabrada	Madrid
Spain	Otsuka Investigational Site	Granada
Spain	Otsuka Investigational Site	Madrid
Spain	Otsuka Investigational Site	Madrid
United Kingdom	Otsuka Investigational Site	Chertsey	Surrey
United States	Otsuka Investigational Site	Germantown	Tennessee
United States	Otsuka Investigational Site	Hollywood	Florida
United States	Otsuka Investigational Site	Houston	Texas
United States	Otsuka Investigational Site	Jacksonville	Florida
United States	Otsuka Investigational Site	Johnson City	New York
United States	Otsuka Investigational Site	Lexington	Kentucky
United States	Otsuka Investigational Site	New Orleans	Louisiana
United States	Otsuka Investigational Site	Sarasota	Florida
United States	Otsuka Investigational Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.

Countries where clinical trial is conducted

United States,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Peak plasma concentration (Cmax)		24 hours	No
Primary	Part 1: Area under the concentration-time curve (AUCt)		24 hours	No
Primary	Part 1:QT interval corrected for heart rate using the Fridericia formula (QTcF)	QT= Uncorrected interval from onset of QRS complex to end of T wave. Measured using Holter monitor and local ECG readings.	24 hours	Yes
Primary	Part 1: Ventricular rate		24 hours	Yes
Primary	Part 1: Diastolic and systolic blood pressure		24 hours	Yes
Primary	Part 2: Percent of subjects with normal sinus rhythm (NSR)		30 minutes	No
Primary	Part 2/1 infusion: Cmax		24 hours	No
Primary	Part 2/2 infusions: Cmax		24 hours	No
Primary	Part 2/1 infusion: AUCt		24 hours	No
Primary	Part 2/2 infusions: AUCt		24 hours	No
Primary	Part 2: QTcF		24 hours	Yes
Primary	Part 2: Ventricular rate		24 hours	Yes
Primary	Part 2: Diastolic and systolic blood pressure		24 hours	Yes
Secondary	Part 1: Percentage of subjects with NSR		24 hours	No
Secondary	Part 2: Time to NSR		24 hours	No
Secondary	Part 2: Duration of NSR		24 hours	No
Secondary	Part 2: Duration of NSR		168 hours	No