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

Ventricular Arrhythmia Clinical Trial

— ALPHEE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00993382
• Other study ID #: DRI10936
• Secondary ID: 2008-008412-47
• Status: Completed
• Phase: Phase 2
• First received: October 9, 2009
• Last updated: October 12, 2013
• Start date: September 2009
• Est. completion date: May 2011

Study information

• Verified date: October 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 486
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Arrhythmia Prophylaxis
• Ventricular Arrhythmia

Intervention

Drug:
• Celivarone (SSR149744)
50 or 100 mg capsules oral administration with a meal
• amiodarone
200 mg capsules oral administration with a meal
• placebo
Matching capsules oral administration with a meal

Locations

Country	Name	City	State
Argentina	Investigational Site Number 032002	Ciudad Autonoma De Bs.As
Argentina	Investigational Site Number 032003	Corrientes
Argentina	Investigational Site Number 032004	San Miguel De Tucuman
Australia	Investigational Site Number 036012	Adelaide
Australia	Investigational Site Number 036006	Auchenflower
Australia	Investigational Site Number 036004	Bedford Park
Australia	Investigational Site Number 036014	Camperdown
Australia	Investigational Site Number 036013	Garran
Australia	Investigational Site Number 036010	Gosford
Australia	Investigational Site Number 036005	Herston
Australia	Investigational Site Number 036008	Nedlands
Australia	Investigational Site Number 036009	New Lambton
Australia	Investigational Site Number 036007	Perth
Australia	Investigational Site Number 036003	Woolloongabba
Belgium	Investigational Site Number 056005	Aalst
Belgium	Investigational Site Number 056007	Brugge
Belgium	Investigational Site Number 056001	Brussel
Belgium	Investigational Site Number 056002	Gilly
Belgium	Investigational Site Number 056004	Hasselt
Belgium	Investigational Site Number 056003	Roeselare
Canada	Investigational Site Number 124009	Calgary
Canada	Investigational Site Number 124010	Hamilton
Canada	Investigational Site Number 124004	London
Canada	Investigational Site Number 124001	Montreal
Canada	Investigational Site Number 124008	Montreal
Canada	Investigational Site Number 124005	Ste-Foy
Canada	Investigational Site Number 124002	Toronto
Canada	Investigational Site Number 124006	Vancouver
Canada	Investigational Site Number 124007	Victoria
Chile	Investigational Site Number 152001	Santiago
Czech Republic	Investigational Site Number 203004	Brno
Czech Republic	Investigational Site Number 203002	Ceske Budejovice
Czech Republic	Investigational Site Number 203005	Hradec Kralove
Czech Republic	Investigational Site Number 203001	Liberec
Czech Republic	Investigational Site Number 203003	Olomouc
Czech Republic	Investigational Site Number 203006	Praha 5
Denmark	Investigational Site Number 208002	Aarhus
Denmark	Investigational Site Number 208004	Hellerup
Denmark	Investigational Site Number 208005	København Ø
Denmark	Investigational Site Number 208001	Odense C
Finland	Investigational Site Number 246001	Helsinki
Finland	Investigational Site Number 246004	Tampere
France	Investigational Site Number 250004	Brest
France	Investigational Site Number 250006	Grenoble
France	Investigational Site Number 250005	Lille
France	Investigational Site Number 250002	Montpellier
France	Investigational Site Number 250001	Paris Cedex 15
France	Investigational Site Number 250007	Rennes
France	Investigational Site Number 250003	Vandoeuvre Les Nancy Cedex
Germany	Investigational Site Number 276005	Bad Neustadt
Germany	Investigational Site Number 276002	Bernau
Germany	Investigational Site Number 276003	Dresden
Germany	Investigational Site Number 276001	Frankfurt Am Main
Germany	Investigational Site Number 276006	Hamburg
Hungary	Investigational Site Number 348001	Balatonfüred
Hungary	Investigational Site Number 348004	Budapest
Hungary	Investigational Site Number 348005	Pécs
Hungary	Investigational Site Number 348003	Zalaegerszeg
Israel	Investigational Site Number 376002	Afula
Israel	Investigational Site Number 376003	Ashkelon
Israel	Investigational Site Number 376004	Haifa
Israel	Investigational Site Number 376001	Tel Aviv
Italy	Investigational Site Number 380004	Bari
Italy	Investigational Site Number 380008	Bergamo
Italy	Investigational Site Number 380002	Como
Italy	Investigational Site Number 380001	Firenze
Italy	Investigational Site Number 380007	Roma
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
Mexico	Investigational Site Number 484002	Mexico City
Netherlands	Investigational Site Number 528001	Alkmaar
Netherlands	Investigational Site Number 528005	Amsterdam
Netherlands	Investigational Site Number 528002	Breda
Netherlands	Investigational Site Number 528003	Maastricht
Netherlands	Investigational Site Number 528007	Rotterdam
Netherlands	Investigational Site Number 528004	Zwolle
Norway	Investigational Site Number 578003	Drammen
Poland	Investigational Site Number 616007	Bydgoszcz
Poland	Investigational Site Number 616011	Gdynia
Poland	Investigational Site Number 616003	Lodz
Poland	Investigational Site Number 616006	Lodz
Poland	Investigational Site Number 616002	Szczecin
Poland	Investigational Site Number 616001	Warszawa
Poland	Investigational Site Number 616008	Warszawa
Portugal	Investigational Site Number 620004	Coimbra
Portugal	Investigational Site Number 620003	Lisboa
Portugal	Investigational Site Number 620005	Vila Nova De Gaia
Russian Federation	Investigational Site Number 643006	Ekaterinburg
Russian Federation	Investigational Site Number 643005	Moscow
Russian Federation	Investigational Site Number 643008	Samara
Russian Federation	Investigational Site Number 643003	St-Petersburg
Russian Federation	Investigational Site Number 643011	St-Petersburg
Russian Federation	Investigational Site Number 643004	Tomsk
Russian Federation	Investigational Site Number 643007	Tyumen
Slovakia	Investigational Site Number 703001	Bratislava
Slovakia	Investigational Site Number 703002	Kosice
South Africa	Investigational Site Number 710002	Pretoria
Spain	Investigational Site Number 724001	Barcelona
Spain	Investigational Site Number 724002	Barcelona
Spain	Investigational Site Number 724003	Madrid
Spain	Investigational Site Number 724004	Madrid
Spain	Investigational Site Number 724006	Santiago De Compostela
Spain	Investigational Site Number 724009	Sevilla
Spain	Investigational Site Number 724007	Valencia
Sweden	Investigational Site Number 752002	Stockholm
Sweden	Investigational Site Number 752003	Umeå
Sweden	Investigational Site Number 752001	Uppsala
Turkey	Investigational Site Number 792001	Ankara
Turkey	Investigational Site Number 792002	Istanbul
Turkey	Investigational Site Number 792003	Istanbul
United States	Investigational Site Number 840009	Ann Arbor	Michigan
United States	Investigational Site Number 840004	Augusta	Georgia
United States	Investigational Site Number 840024	Camp Hill	Pennsylvania
United States	Investigational Site Number 840020	Charleston	South Carolina
United States	Investigational Site Number 840025	Chesapeake	Virginia
United States	Investigational Site Number 840045	Chicago	Illinois
United States	Investigational Site Number 840039	Colorado Springs	Colorado
United States	Investigational Site Number 840049	Columbia	Missouri
United States	Investigational Site Number 840026	Detroit	Michigan
United States	Investigational Site Number 840030	Doylestown	Pennsylvania
United States	Investigational Site Number 840002	Fort Myers	Florida
United States	Investigational Site Number 840006	Huntsville	Alabama
United States	Investigational Site Number 840017	Kansas City	Kansas
United States	Investigational Site Number 840019	Kansas City	Missouri
United States	Investigational Site Number 840035	Lombard	Illinois
United States	Investigational Site Number 840014	Mesa	Arizona
United States	Investigational Site Number 840042	Mobile	Alabama
United States	Investigational Site Number 840031	New York	New York
United States	Investigational Site Number 840012	Norfolk	Virginia
United States	Investigational Site Number 840010	Orlando	Florida
United States	Investigational Site Number 840003	Petoskey	Michigan
United States	Investigational Site Number 840032	Phoenix	Arizona
United States	Investigational Site Number 840005	Port Charlotte	Florida
United States	Investigational Site Number 840037	Portland	Oregon
United States	Investigational Site Number 840048	Rapid City	South Dakota
United States	Investigational Site Number 840054	Redondo Beach	California
United States	Investigational Site Number 840007	Redwood City	California
United States	Investigational Site Number 840038	Richmond	Virginia
United States	Investigational Site Number 840022	Scarborough	Maine
United States	Investigational Site Number 840016	Spokane	Washington
United States	Investigational Site Number 840013	St. Petersburg	Florida
United States	Investigational Site Number 840043	St. Petersburg	Florida
United States	Investigational Site Number 840033	Tucson	Arizona
United States	Investigational Site Number 840011	Tullahoma	Tennessee
United States	Investigational Site Number 840029	Tulsa	Oklahoma
United States	Investigational Site Number 840034	Upland	Pennsylvania
United States	Investigational Site Number 840015	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  Chile,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Russian Federation,  Slovakia,  South Africa,  Spain,  Sweden,  Turkey, 

References & Publications (1)

Kowey PR, Crijns HJ, Aliot EM, Capucci A, Kulakowski P, Radzik D, Roy D, Connolly SJ, Hohnloser SH; ALPHEE Study Investigators. Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator fo — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Ventricular Tachycardia or Ventricular Fibrillation (VT/VF) triggered ICD interventions or sudden death	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.	up to 20 months (median follow-up of 12 months)	No
Secondary	Time to ICD shocks (appropriate or inappropriate) or death from any cause		up to 20 months (median follow-up of 12 months)	No
Secondary	Time to Cardiovascular hospitalization or death		up to 20 months (median follow-up of 12 months)	No