Paroxysmal Atrial Fibrillation
Conditions
Keywords
Atrial Fibrillation, Paroxysmal Atrial Fibrillation, AF
Brief summary
The purpose of this study is to evaluate whether treatment with ISIS CRP Rx can reduce AF (Atrial Fibrillation) burden (percentage of time spent in AF) in subjects with paroxysmal AF
Interventions
DRUGISIS CRP Rx
DRUGPlacebo
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male of female; age over 18 years * Dual chamber permanent pacemaker implanted * Confirmed diagnosis of paroxysmal atrial fibrillation with an AF burden of 1 to 50%, as derived from pacemaker diagnostic algorithms * Able to have pacemaker antiarrhythmic algorithms turned off for the duration of the study * Able to discontinue all Class I and III antiarrhythmic medication for the duration of the study * Therapeutically anticoagulated with warfarin or dabigatran, and anticipated to be for duration of the study * High sensitivity C-Reactive Protein (hsCRP) between 2 and 10 mg/L (inclusive)
Exclusion criteria
* Clinically significant abnormalities in medical history, physical examination, or screening laboratory results that would render a subject unsuitable for inclusion * NYHA class III/IV heart failure * Impaired left ventricular function of less than 45% determined by echocardiography within 3 months of screening * Moderate or greater mitral regurgitation assessed by echocardiography within 3 months of screening * Permanent AF * Continuous Amiodarone therapy within 90 days prior to Study Day 1 * Treatment with another Study Drug, biological agent, or device within one-month of screening, or five half-lives of study agent, whichever is longer * Use of systemic corticosteroids or other anti-inflammatory medications including non-steroidal anti-inflammatory drugs (NSAIDs) * Use of statins, ACE inhibitors or AT-receptor antagonists unless on a stable regimen for at least 3 months prior to dosing and will remain on a stable regimen for the duration of the study * Uncontrolled hypertension (BP \>160/100) * Current or expected use of any anticoagulant apart from warfarin or dabigatran
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AF burden reduction | 113 Days | Burden measured as percentage of time spent in AF as derived from continuous pacemaker monitoring |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the effect of ISIS CRP Rx on ventricular rate during sinus rhythm | 113 Days | — |
| To assess the effect of ISIS CRP Rx on measures of Quality of Life | 113 Days | — |
| To assess whether treatment with ISIS CRP Rx reduces hsCRP in subjects with paroxysmal AF | 113 Days | Change from Baseline will be compared for each treatment period |
| To assess the effect of ISIS CRP Rx on the: | 113 Days | * total number of AF episodes * average duration of AF per episode * average sinus rhythm duration * atrial and ventricular rate during AF episodes |
| To assess the tolerability of ISIS CRP Rx in subjects with paroxysmal AF | 113 Days | Incidence rates of all Adverse Events will be tabulated by MedRA system Organ Class and by MedRA Term for each treatment group. Lab Tests, Vital Signs, And ECG Parameters will be summarized by study visit for each treatment group. |
| To assess the pharmacokinetics of ISIS CRP Rx in subjects with paroxysmal AF | 113 Days | Trough levels of ISIS CRP Rx will be assessed at intervals throughout the study |
| To assess the safety of ISIS CRP Rx in subjects with paroxysmal AF | 113 Days | Incidence rates of all Adverse Events will be tabulated by MedRA system Organ Class and by MedRA Term for each treatment group. Lab Tests, Vital Signs, And ECG Parameters will be summarized by study visit for each treatment group. |
Countries
United Kingdom
Outcome results
None listed