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Vernakalant (Oral) Prevention of Atrial Fibrillation Recurrence Post-Conversion Study
This study has been completed.
Sponsored by: Cardiome Pharma
Information provided by: Cardiome Pharma
ClinicalTrials.gov Identifier: NCT00526136
  Purpose

To evaluate the safety, tolerability and efficacy of 3 doses of vernakalant (oral) (150 mg, 300 mg and 500 mg b.i.d.) administered for up to 90 days in subjects with sustained symptomatic atrial fibrillation (AF duration > 72 hours and < 6 months).


Condition Intervention Phase
Atrial Fibrillation
Drug: Placebo
Drug: Vernakalant (oral)
Phase II

Genetics Home Reference related topics: Brugada syndrome familial atrial fibrillation short QT syndrome
Drug Information available for: RSD 1235
U.S. FDA Resources
Study Type: Interventional
Study Design: Prevention, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: Vernakalant (Oral) Prevention of Atrial Fibrillation Recurrence Post-Conversion Study

Further study details as provided by Cardiome Pharma:

Primary Outcome Measures:
  • Time to first documented recurrence of symptomatic sustained AF. [ Time Frame: Time to first documented recurrence of symptomatic sustained AF within Day 90 of dosing ] [ Designated as safety issue: No ]
  • Safety assessments- Vital signs, safety laboratory assays, ECG parameters, physical examinations, and frequency of adverse events [ Time Frame: Safety assessments within Day 120 of dosing ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to first documented recurrence of symptomatic or asymptomatic sustained AF [ Time Frame: Time to first documented recurrence of symptomatic or asymptomatic sustained AF within 90 days of dosing ] [ Designated as safety issue: No ]
  • Time to first documented recurrence of symptomatic AF [ Time Frame: Time to first documented recurrence of symptomatic AF within 90 days of dosing ] [ Designated as safety issue: No ]
  • Time to first documented recurrence of symptomatic or asymptomatic AF [ Time Frame: Time to first documented recurrence of symptomatic or asymptomatic AF within 90 days of dosing ] [ Designated as safety issue: No ]
  • Proportion of subjects in sinus rhythm on Day 90. [ Time Frame: Proportion of subjects in sinus rhythm on Day 90 of dosing ] [ Designated as safety issue: No ]
  • Improvement in AF symptoms as assessed by an AF symptom checklist. [ Time Frame: Improvement in AF symptoms as assessed by an AF symptom checklist within Day 90 of dosing ] [ Designated as safety issue: No ]
  • Improvement in QOL as measured by SF-36 [ Time Frame: Improvement in QOL as measured by SF-36 within Day 90 of dosing ] [ Designated as safety issue: No ]

Enrollment: 735
Study Start Date: March 2007
Study Completion Date: July 2008
Arms Assigned Interventions
1: Placebo Comparator
Placebo (b.i.d.)
Drug: Placebo
2: Experimental
Vernakalant (oral), 150 mg (b.i.d.)
Drug: Vernakalant (oral)
Vernakalant (oral), 150 mg (b.i.d.) Vernakalant (oral), 300 mg (b.i.d.) Vernakalant (oral), 500 mg (b.i.d.)
3: Experimental
Vernakalant (oral), 300 mg (b.i.d.)
Drug: Vernakalant (oral)
Vernakalant (oral), 150 mg (b.i.d.) Vernakalant (oral), 300 mg (b.i.d.) Vernakalant (oral), 500 mg (b.i.d.)
4: Experimental
Vernakalant (oral), 500 mg (b.i.d.)
Drug: Vernakalant (oral)
Vernakalant (oral), 150 mg (b.i.d.) Vernakalant (oral), 300 mg (b.i.d.) Vernakalant (oral), 500 mg (b.i.d.)

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Comprehend and sign a written informed consent form, (per local and national regulations, as applicable)
  • Be 18 to 85 years of age
  • Women must not be pregnant, be non-nursing and if pre-menopausal, must be using an effective form of birth control from time of screening until 3 months after the last dose of medication. Methods of birth control considered to be effective may include hormonal contraception (the pill), an intrauterine device (IUD), condoms in combination with a spermicidal cream, total abstinence or sterilisation. Men should be advised not to conceive a child and are advised to use an effective form of birth control from admission until 3 months after the last dose of study medication
  • Have symptomatic AF that has been sustained for greater than 72 hours and less than 6 months duration and is clinically indicated for cardioversion;
  • Have adequate anticoagulant therapy for cardioversion in accordance with standard of practice as recommended by ACC/AHA/ESC guidelines (Fuster V. et al, 2006);
  • Be haemodynamically stable (100 mmHg < systolic blood pressure < 190 mmHg) at screening and on Day 1 before dosing (while taking rate control drugs, if required). After resting supine for 3 minutes, blood pressures should be measured 3 times in 5 minutes with at least 1 minute between assessments;
  • Have a body weight between 45 and 113 kg (99 and 250 lbs).

Exclusion Criteria:

  • Have known prolonged QT syndrome or QTcB interval of >0.500 sec as measured at screening on a 12 lead ECG; familial long QT syndrome; previous Torsades de Pointes; ventricular fibrillation; or sustained ventricular tachycardia (VT).
  • Have a QRS >0.140 sec;
  • Documented previous episodes of second or third-degree atrioventricular block;
  • Have clinically significant persistent bradycardia with ventricular rate below 50 beats/min, sick-sinus syndrome or pacemaker;
  • Have clinically significant moderate or severe aortic valvular stenosis (gradient >25 mmHg), hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis;
  • Have Class III or Class IV congestive heart failure at screening or admission, or have been hospitalized for heart failure in the previous 6 months;
  • Have a myocardial infarction (MI), cardiac surgery, angioplasty, unstable angina or acute coronary syndrome within 30 days prior to entry into the study; h) Have serious pulmonary, hepatic, metabolic, renal (serum creatinine > 2.0 mg/dl), gastrointestinal, central nervous system (CNS) or psychiatric disease, end-stage disease states, or any other disease that could interfere with the conduct or validity of the study or compromise subject safety;
  • Have known concurrent temporary secondary causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, pneumonia, hypoxemia (oxygen saturation < 90% on room air), acute pericarditis, or myocarditis;
  • Potassium (K+) <3.5 mmol/L or >5.5 mmol/L or magnesium (Mg2+) below the lower limit of normal (Mg2+< 0.65 mmol/L in subjects 65 years or younger and <0.80 mmol/L in subjects 66 years or older). (Both K+ and Mg2+ should be corrected prior to dosing);
  • Have clinical evidence of digoxin toxicity;
  • Have received an oral Class I or Class III antiarrhythmic agent (including sotalol) within 3 days of randomisation or oral amiodarone within 4 weeks, or have received intravenous Class I or Class III antiarrhythmic agent or i.v. amiodarone within 24 hours prior to start of dosing;
  • Have any other surgical or medical condition that, in the judgment of the clinical Investigator might warrant exclusion or be contraindicated for safety reasons;
  • Be concurrently participating in another drug study or have received an investigational drug within 30 days prior to screening;
  • Be unable to communicate well with the Investigator and to comply with the requirements of the entire study;
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00526136

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Sponsors and Collaborators
Cardiome Pharma
Investigators
Study Director: Gregory Beatch, PhD Cardiome Pharma
  More Information

Related Info  This link exits the ClinicalTrials.gov site

Responsible Party: Cardiome Pharma Corp. ( Gregory Beatch, Ph.D., Vice President, Scientific Affairs )
Study ID Numbers: 1235-SR-202-AF
Study First Received: September 5, 2007
Last Updated: December 17, 2008
ClinicalTrials.gov Identifier: NCT00526136  
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration;   Australia: Human Research Ethics Committee;   Belgium: Federal Agency for Medicinal Products and Health Products;   Belgium: Institutional Review Board;   Bulgaria: Bulgarian Drug Agency;   Bulgaria: Ministry of Health;   Croatia: Ethics Committee;   Croatia: Ministry of Health and Social Care;   Czech Republic: Ethics Committee;   Czech Republic: State Institute for Drug Control;   Denmark: Danish Dataprotection Agency;   Denmark: Danish Medicines Agency;   Denmark: Ethics Committee;   Estonia: The State Agency of Medicine;   Germany: Federal Institute for Drugs and Medical Devices;   Hungary: National Institute of Pharmacy;   Lithuania: Bioethics Committee;   Lithuania: State Medicine Control Agency - Ministry of Health;   Netherlands: The Central Committee on Research Involving Human Subjects (CCMO);   Netherlands: Medical Ethics Review Committee (METC);   New Zealand: Medsafe;   Poland: Ministry of Health;   Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products;   Portugal: National Pharmacy and Medicines Institute;   Romania: Ministry of Public Health;   Romania: National Medicines Agency;   Russia: Ethics Committee;   Russia: FSI Scientific Center of Expertise of Medical Application;   Serbia and Montenegro: Agency for Drugs and Medicinal Devices;   Serbia: Ethics Committee;   Singapore: Health Sciences Authority;   Slovakia: State Institute for Drug Control;   South Africa: Medicines Control Council;   Spain: Ministry of Health and Consumption;   Sweden: Medical Products Agency;   Switzerland: Swissmedic;   Ukraine: State Pharmacological Center - Ministry of Health

Keywords provided by Cardiome Pharma:
Atrial Fibrillation

Study placed in the following topic categories:
Heart Diseases
Atrial Fibrillation
Recurrence
Arrhythmias, Cardiac

Additional relevant MeSH terms:
Pathologic Processes
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 16, 2009