Dose Ranging Study of Celivarone With Amiodarone as Calibrator for the Prevention of Implantable Cardioverter Defibrillator (ICD) Interventions or Death (ALPHEE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00993382
First received: October 9, 2009
Last updated: October 12, 2013
Last verified: October 2013
  Purpose

The Primary Objective was to assess the efficacy of celivarone for the prevention of Implantable Cardioverter Defibrillator (ICD) interventions or death.

Secondary Objectives were:

  • To assess the tolerability and safety of the different dose regimens of celivarone in the selected population.
  • To document SSR149744 plasma levels during the study.

Condition Intervention Phase
Arrhythmia Prophylaxis
Ventricular Arrhythmia
Drug: Celivarone (SSR149744)
Drug: amiodarone
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Double Blind Placebo Controlled Dose Ranging Study of the Efficacy and Safety of Celivarone at 50, 100 or 300 mg OD With Amiodarone as Calibrator for the Prevention of ICD Interventions or Death

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Time to Ventricular Tachycardia or Ventricular Fibrillation (VT/VF) triggered ICD interventions or sudden death [ Time Frame: up to 20 months (median follow-up of 12 months) ] [ Designated as safety issue: No ]

    The presence of VT or VF was documented by ICD interrogation leading to any ICD interventions (shocks or antittachycardia pacing).

    The 10 first ICD interventions for each patient were centrally and blindly adjudicated by an Adjudication Committee.



Secondary Outcome Measures:
  • Time to ICD shocks (appropriate or inappropriate) or death from any cause [ Time Frame: up to 20 months (median follow-up of 12 months) ] [ Designated as safety issue: No ]
  • Time to Cardiovascular hospitalization or death [ Time Frame: up to 20 months (median follow-up of 12 months) ] [ Designated as safety issue: No ]

Enrollment: 486
Study Start Date: September 2009
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: celivarone 50 mg
Celivarone 50 mg capsule once daily up to 10-15 days before the common study end date
Drug: Celivarone (SSR149744)

50 or 100 mg capsules

oral administration with a meal

Drug: placebo

Matching capsules

oral administration with a meal

Experimental: celivarone 100 mg
Celivarone 100 mg once daily up to 10-15 days before the common study end date
Drug: Celivarone (SSR149744)

50 or 100 mg capsules

oral administration with a meal

Drug: placebo

Matching capsules

oral administration with a meal

Experimental: celivarone 300 mg
Celivarone 300 mg once daily up to 10-15 days before the common study end date
Drug: Celivarone (SSR149744)

50 or 100 mg capsules

oral administration with a meal

Active Comparator: amiodarone 200 mg
Amiodarone 600 mg once daily for 10 days (loading dose) then 200 mg once daily up to 10-15 days before the common study end date
Drug: amiodarone

200 mg capsules

oral administration with a meal

Drug: placebo

Matching capsules

oral administration with a meal

Placebo Comparator: placebo
Placebo once daily up to 10-15 days before the common study end date
Drug: placebo

Matching capsules

oral administration with a meal


Detailed Description:

The study included a one week screening period, followed by a treatment period ranging between 6 and 19 months.

The treatment was to be continued until the End of Treatment visit scheduled 10-15 days prior to the common Scheduled Study End Date (SSED). The SSED was defined as about 190 days after the last patient randomization date.

The expected recruitment duration was about 14 months and thus the total duration of the study about 20 months. Visits were planned to be performed at baseline, after 5 days, after 14 days, every month for 6 months and then, every three months after 6 months until the end of the study.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Implantable Cardioverter Defibrillator (ICD) patients with a Left Ventricular Ejection Fraction (LVEF) of 40% or less AND one of the following criteria:

    • at least one ICD therapy for Ventricular Tachycardia (VT) OR
    • Ventricular Fibrillation (VF) in the previous month OR
    • ICD implantation in the previous month for documented VT/VF

Exclusion criteria :

  • Patients of either sex aged below 21 years (or the age of legal consent of the country),
  • Women of childbearing potential without adequate birth control or pregnant or breastfeeding women
  • Patients with known ICD lead problem (lead dislodgement)
  • ICD without the following characteristics :

    • data logging function with cumulative counting of device intervention (shocks and antitachycardia pacing [ATP])
    • electrogram storage capabilities
    • ventricular demand pacing.
  • Recent unstable angina pectoris or myocardial infarction (< 4 weeks),
  • History of torsades de pointes,
  • Genetic channelopathies including congenital long QT syndrome,
  • Wolff-Parkinson-White syndrome,
  • Patients in unstable hemodynamic condition such as acute pulmonary edema within 12 hours prior to start of study medication; cardiogenic shock; treatment with intravenous pressor agents; patients on respirator; congestive heart failure of stage New York Heart Association (NYHA) IV within the last 4 weeks; uncorrected, hemodynamically significant primary obstructive valvular disease; hemodynamically significant obstructive cardiomyopathy; a cardiac operation or revascularization procedure within 4 weeks preceding randomization,
  • Incessant sustained VT/VF (VT/VF that recurs promptly despite termination attempts) during the three days preceding randomization.
  • Patients with inappropriate (not triggered by VT nor VF) shocks during the month preceding randomization.
  • Clinically relevant haematologic, hepatobiliary (ALT, AST > 3 times the upper limit of normal at randomization), gastro-intestinal, renal (serum creatinine > 221 µmol/l (2.5 mg/dl) at randomization), pulmonary, endocrinologic or psychiatric disease.
  • Patients treated with oral amiodarone (more than 20 tablets during the 2 months preceding randomization)

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00993382

  Hide Study Locations
Locations
United States, Alabama
Investigational Site Number 840006
Huntsville, Alabama, United States, 35801
Investigational Site Number 840042
Mobile, Alabama, United States, 36608
United States, Arizona
Investigational Site Number 840014
Mesa, Arizona, United States, 85206
Investigational Site Number 840032
Phoenix, Arizona, United States, 85006
Investigational Site Number 840033
Tucson, Arizona, United States, 85723
United States, California
Investigational Site Number 840054
Redondo Beach, California, United States, 90277
Investigational Site Number 840007
Redwood City, California, United States, 94062
United States, Colorado
Investigational Site Number 840039
Colorado Springs, Colorado, United States, 80909
United States, Florida
Investigational Site Number 840002
Fort Myers, Florida, United States, 33908
Investigational Site Number 840010
Orlando, Florida, United States, 32806
Investigational Site Number 840005
Port Charlotte, Florida, United States, 33952-8008
Investigational Site Number 840043
St. Petersburg, Florida, United States, 33707
Investigational Site Number 840013
St. Petersburg, Florida, United States, 33707
United States, Georgia
Investigational Site Number 840004
Augusta, Georgia, United States, 30901
United States, Illinois
Investigational Site Number 840045
Chicago, Illinois, United States, 60637
Investigational Site Number 840035
Lombard, Illinois, United States, 60148
United States, Kansas
Investigational Site Number 840017
Kansas City, Kansas, United States, 66160
United States, Maine
Investigational Site Number 840022
Scarborough, Maine, United States, 04074
United States, Michigan
Investigational Site Number 840009
Ann Arbor, Michigan, United States, 48109-0759
Investigational Site Number 840026
Detroit, Michigan, United States, 48236
Investigational Site Number 840003
Petoskey, Michigan, United States, 49770
Investigational Site Number 840015
Ypsilanti, Michigan, United States, 48197
United States, Missouri
Investigational Site Number 840049
Columbia, Missouri, United States, 65201
Investigational Site Number 840019
Kansas City, Missouri, United States, 64114
United States, New York
Investigational Site Number 840031
New York, New York, United States, 10001
United States, Oklahoma
Investigational Site Number 840029
Tulsa, Oklahoma, United States, 74104
United States, Oregon
Investigational Site Number 840037
Portland, Oregon, United States, 97201-3098
United States, Pennsylvania
Investigational Site Number 840024
Camp Hill, Pennsylvania, United States, 17011
Investigational Site Number 840030
Doylestown, Pennsylvania, United States, 18901
Investigational Site Number 840034
Upland, Pennsylvania, United States, 19013
United States, South Carolina
Investigational Site Number 840020
Charleston, South Carolina, United States, 29406
United States, South Dakota
Investigational Site Number 840048
Rapid City, South Dakota, United States, 57701
United States, Tennessee
Investigational Site Number 840011
Tullahoma, Tennessee, United States, 37388
United States, Virginia
Investigational Site Number 840025
Chesapeake, Virginia, United States, 23320
Investigational Site Number 840012
Norfolk, Virginia, United States, 23507
Investigational Site Number 840038
Richmond, Virginia, United States, 23225
United States, Washington
Investigational Site Number 840016
Spokane, Washington, United States, 99204
Argentina
Investigational Site Number 032002
Ciudad Autonoma De Bs.As, Argentina, 1428
Investigational Site Number 032003
Corrientes, Argentina, 3400
Investigational Site Number 032004
San Miguel De Tucuman, Argentina, T4000NIL
Australia
Investigational Site Number 036012
Adelaide, Australia, 5000
Investigational Site Number 036006
Auchenflower, Australia, 4066
Investigational Site Number 036004
Bedford Park, Australia, 5042
Investigational Site Number 036014
Camperdown, Australia, 2050
Investigational Site Number 036013
Garran, Australia, 2605
Investigational Site Number 036010
Gosford, Australia, 2250
Investigational Site Number 036005
Herston, Australia, 4029
Investigational Site Number 036008
Nedlands, Australia, 6009
Investigational Site Number 036009
New Lambton, Australia, 2305
Investigational Site Number 036007
Perth, Australia, 6000
Investigational Site Number 036003
Woolloongabba, Australia, 4102
Belgium
Investigational Site Number 056005
Aalst, Belgium, 9300
Investigational Site Number 056007
Brugge, Belgium, 8000
Investigational Site Number 056001
Brussel, Belgium, 1090
Investigational Site Number 056002
Gilly, Belgium, 6060
Investigational Site Number 056004
Hasselt, Belgium, 3500
Investigational Site Number 056003
Roeselare, Belgium, 8800
Canada
Investigational Site Number 124009
Calgary, Canada, T2N 2T9
Investigational Site Number 124010
Hamilton, Canada, L8L 2X2
Investigational Site Number 124004
London, Canada, N6A 5A5
Investigational Site Number 124001
Montreal, Canada, H2W 1T8
Investigational Site Number 124008
Montreal, Canada, H1T 1C8
Investigational Site Number 124005
Ste-Foy, Canada, G1V 4G5
Investigational Site Number 124002
Toronto, Canada, M5B 1W8
Investigational Site Number 124006
Vancouver, Canada, V6E 1M9
Investigational Site Number 124007
Victoria, Canada, V8R 4R2
Chile
Investigational Site Number 152001
Santiago, Chile, 8380456
Czech Republic
Investigational Site Number 203004
Brno, Czech Republic, 65691
Investigational Site Number 203002
Ceske Budejovice, Czech Republic, 37087
Investigational Site Number 203005
Hradec Kralove, Czech Republic, 50005
Investigational Site Number 203001
Liberec, Czech Republic, 46063
Investigational Site Number 203003
Olomouc, Czech Republic, 77520
Investigational Site Number 203006
Praha 5, Czech Republic, 15030
Denmark
Investigational Site Number 208002
Aarhus, Denmark, 8200
Investigational Site Number 208004
Hellerup, Denmark, 2900
Investigational Site Number 208005
København Ø, Denmark, 2100
Investigational Site Number 208001
Odense C, Denmark, 5000
Finland
Investigational Site Number 246001
Helsinki, Finland, 00290
Investigational Site Number 246004
Tampere, Finland, 33520
France
Investigational Site Number 250004
Brest, France, 29609
Investigational Site Number 250006
Grenoble, France, 38043
Investigational Site Number 250005
Lille, France, 59037
Investigational Site Number 250002
Montpellier, France, 34295
Investigational Site Number 250001
Paris Cedex 15, France, 75908
Investigational Site Number 250007
Rennes, France, 35033
Investigational Site Number 250003
Vandoeuvre Les Nancy Cedex, France, 54511
Germany
Investigational Site Number 276005
Bad Neustadt, Germany, 97616
Investigational Site Number 276002
Bernau, Germany, 16321
Investigational Site Number 276003
Dresden, Germany, 01099
Investigational Site Number 276001
Frankfurt Am Main, Germany, 60590
Investigational Site Number 276006
Hamburg, Germany, 20246
Hungary
Investigational Site Number 348001
Balatonfüred, Hungary, 8230
Investigational Site Number 348004
Budapest, Hungary, 1027
Investigational Site Number 348005
Pécs, Hungary, 7624
Investigational Site Number 348003
Zalaegerszeg, Hungary, 8900
Israel
Investigational Site Number 376002
Afula, Israel, 18101
Investigational Site Number 376003
Ashkelon, Israel, 78278
Investigational Site Number 376004
Haifa, Israel, 31048
Investigational Site Number 376001
Tel Aviv, Israel, 64239
Italy
Investigational Site Number 380004
Bari, Italy, 70124
Investigational Site Number 380008
Bergamo, Italy, 24125
Investigational Site Number 380002
Como, Italy, 22100
Investigational Site Number 380001
Firenze, Italy, 50141
Investigational Site Number 380007
Roma, Italy, 00169
Japan
Investigational Site Number 392004
Meguro-Ku, Japan
Investigational Site Number 392005
Niigata-Shi, Japan
Investigational Site Number 392001
Osaka Sayama-Shi, Japan
Investigational Site Number 392006
Osaka-Shi, Japan
Investigational Site Number 392003
Shinjuku-Ku, Japan
Investigational Site Number 392002
Suita-Shi, Japan
Mexico
Investigational Site Number 484002
Mexico City, Mexico, 14080
Netherlands
Investigational Site Number 528001
Alkmaar, Netherlands, 1815 JD
Investigational Site Number 528005
Amsterdam, Netherlands, 1091 AC
Investigational Site Number 528002
Breda, Netherlands, 4818 CK
Investigational Site Number 528003
Maastricht, Netherlands, 6229 HX
Investigational Site Number 528007
Rotterdam, Netherlands, 3015 CE
Investigational Site Number 528004
Zwolle, Netherlands, 8011 JW
Norway
Investigational Site Number 578003
Drammen, Norway, 3004
Poland
Investigational Site Number 616007
Bydgoszcz, Poland, 85-094
Investigational Site Number 616011
Gdynia, Poland, 81-348
Investigational Site Number 616006
Lodz, Poland, 90-548
Investigational Site Number 616003
Lodz, Poland, 91-425
Investigational Site Number 616002
Szczecin, Poland, 70-111
Investigational Site Number 616008
Warszawa, Poland, 02-097
Investigational Site Number 616001
Warszawa, Poland, 04-073
Portugal
Investigational Site Number 620004
Coimbra, Portugal, 3000-075
Investigational Site Number 620003
Lisboa, Portugal, 1169-024
Investigational Site Number 620005
Vila Nova De Gaia, Portugal, 4430-502
Russian Federation
Investigational Site Number 643006
Ekaterinburg, Russian Federation, 620102
Investigational Site Number 643005
Moscow, Russian Federation, 650002
Investigational Site Number 643008
Samara, Russian Federation, 443070
Investigational Site Number 643003
St-Petersburg, Russian Federation, 197110
Investigational Site Number 643011
St-Petersburg, Russian Federation, 199106
Investigational Site Number 643004
Tomsk, Russian Federation, 634012
Investigational Site Number 643007
Tyumen, Russian Federation, 625023
Slovakia
Investigational Site Number 703001
Bratislava, Slovakia, 81104
Investigational Site Number 703002
Kosice, Slovakia, 04011
South Africa
Investigational Site Number 710002
Pretoria, South Africa, 181
Spain
Investigational Site Number 724001
Barcelona, Spain, 08036
Investigational Site Number 724002
Barcelona, Spain, 08907
Investigational Site Number 724003
Madrid, Spain, 28046
Investigational Site Number 724004
Madrid, Spain, 28035
Investigational Site Number 724006
Santiago De Compostela, Spain, 15706
Investigational Site Number 724009
Sevilla, Spain, 41008
Investigational Site Number 724007
Valencia, Spain, 46026
Sweden
Investigational Site Number 752002
Stockholm, Sweden, 118 83
Investigational Site Number 752003
Umeå, Sweden, 901 85
Investigational Site Number 752001
Uppsala, Sweden, 751 85
Turkey
Investigational Site Number 792001
Ankara, Turkey, 06490
Investigational Site Number 792003
Istanbul, Turkey, 34304
Investigational Site Number 792002
Istanbul, Turkey, 34390
Sponsors and Collaborators
Sanofi
Investigators
Study Chair: Peter KOWEY, Pr Steering Committee Chair Person
  More Information

Publications:
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00993382     History of Changes
Other Study ID Numbers: DRI10936, 2008-008412-47
Study First Received: October 9, 2009
Last Updated: October 12, 2013
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products

Additional relevant MeSH terms:
Amiodarone
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on October 19, 2014