Ascending Dose Study of OPC-108459 Intravenous Infusions in Patients With Paroxysmal and Persistent Atrial Fibrillation (CADENCE 215)
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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 |
- 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 ]
- 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:
|
| 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:
|
| 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:
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 |
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 screening
- 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 taking a moderate or strong CYP3A4 inhibitor less than 5 half-lives before screening
- Subjects who have taken another investigational product within 30 days of dosing
Contacts and Locations| Contact: Study Information | CADENCE215@mmgct.com |
Show 24 Study Locations 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: | October 5, 2012 |
| Health Authority: | United States: Food and Drug Administration |
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 May 23, 2013