Clinical trial NCT01483183: Ascending Dose Study of OPC-108459 Intravenous Infusions in Patients With Paroxysmal and Persistent Atrial Fibrillation
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Atrial Fibrillation
Paroxysmal Atrial Fibrillation
Persistent Atrial Fibrillation
Keywords: Atrial fibrillation
Paroxysmal Atrial fibrillation
Persistent Atrial fibrillation
A-fib
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2011-12-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Part 1: Maximum (Peak) Plasma Concentration (Cmax)
timeFrame: 24 hours
measure: Part 1: Area Under the Concentration-time Curve From Time 0 to Time of the Last Measurable Concentration (AUCτ)
timeFrame: 24 hours
measure: Part 1:Maximal Change From Baseline in QT Interval Corrected for Heart Rate Using the Fridericia Formula (QTcF) Within 24 Hour Infusion
timeFrame: 24 hours
measure: Part 1: Maximal Change From Baseline in Ventricular Rate Within 24 Hour Infusion
timeFrame: 24 hours
measure: Part 1: Maximal Change From Baseline in Blood Pressure Within 24 Hour Infusion
timeFrame: 24 hours
measure: Part 2/1 Infusion: Cmax
timeFrame: 24 hours
measure: Part 2/2 Infusions: Cmax
timeFrame: 24 hours
measure: Part 2/1 Infusion: AUCt
timeFrame: 24 hours
measure: Part 2/2 Infusions: AUCt
timeFrame: 24 hours
measure: Part 2: QTcF
timeFrame: 24 hours
measure: Part 2: Ventricular Rate
timeFrame: 24 hours
measure: Part 2: Diastolic and Systolic Blood Pressure
timeFrame: 24 hours
measure: Part 2: Percentage of Subjects With Normal Sinus Rhythm (NSR)
timeFrame: 24 hours
Secondary outcomes:
measure: Part 1: Percentage of Participants With NSR
timeFrame: 30 minutes
measure: Part 2: Time to NSR
timeFrame: 24 hours
measure: Part 2: Duration of NSR
timeFrame: 24 hours
measure: Part 2: Duration of NSR
timeFrame: 168 hours
Other outcomes:
Locations:
city: Washington
country: United States
facility: Otsuka Investigational Site
state: District of Columbia
city: Hollywood
country: United States
facility: Otsuka Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Otsuka Investigational Site
state: Florida
city: Sarasota
country: United States
facility: Otsuka Investigational Site
state: Florida
city: Lexington
country: United States
facility: Otsuka Investigational Site
state: Kentucky
city: New Orleans
country: United States
facility: Otsuka Investigational Site
state: Louisiana
city: Johnson City
country: United States
facility: Otsuka Investigational Site
state: New York
city: Germantown
country: United States
facility: Otsuka Investigational Site
state: Tennessee
city: Houston
country: United States
facility: Otsuka Investigational Site
state: Texas
city: Berlin
country: Germany
facility: Otsuka Investigational Site
city: Hamburg
country: Germany
facility: Otsuka Investigational Site
city: Leipzig
country: Germany
facility: Otsuka Investigational Site
city: Pirna
country: Germany
facility: Otsuka Investigational Site
city: San Fermo
country: Italy
facility: Otsuka Investigational Site
state: Como
city: Ancona
country: Italy
facility: Otsuka Investigational Site
city: Bologna
country: Italy
facility: Otsuka Investigational Site
city: Cremona
country: Italy
facility: Otsuka Investigational Site
city: Amsterdam
country: Netherlands
facility: Otsuka Investigational Site
city: Groningen
country: Netherlands
facility: Otsuka Investigational Site
city: Fuenlabrada
country: Spain
facility: Otsuka Investigational Site
state: Madrid
city: Barcelona
country: Spain
facility: Otsuka Investigational Site
city: Granada
country: Spain
facility: Otsuka Investigational Site
city: Madrid
country: Spain
facility: Otsuka Investigational Site
city: Madrid
country: Spain
facility: Otsuka Investigational Site
city: Chertsey
country: United Kingdom
facility: Otsuka Investigational Site
state: Surrey
Study officials:
References: