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. - ALPHEE

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2008-008412-47-PL
• Date of registration: 19/06/2009
• Prospective Registration: Yes
• Primary sponsor: Sanofi-aventis Recherche & Développement
• Public 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. - ALPHEE
• Scientific 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. - ALPHEE
• Date of first enrolment: 01/09/2009
• Target sample size: 486
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-008412-47
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Amiodarone is used as a calibrator

Countries of recruitment

Denmark, Finland, France, Germany, Hungary, Italy, Netherlands, Poland, Portugal, Slovakia, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
(All inclusion criteria must be present for the patient to be eligible for the study):

ICD patients with a LVEF of 40% or less AND one of the following criteria:
•at least one ICD therapy for VT or VF in the previous month
•OR ICD implantation in the previous month for documented VT/VF
Signed informed consent for the study

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Methodology related criteria:

E 01. Patients of either sex aged below 21 years (or the age of legal consent of the country),
E 02. Women of childbearing potential without adequate birthcontrol (NB women must be menopaused or sterile or hysterectomized or if women of child-bearing potential they must be on adequate birth control e.g. oral contraception or Intra Uterine Device (IUD).
E 03. Pregnant Women,
E 04. Breastfeeding women,
E 05. Previous (2 preceding months) or current participation in another clinical trial with an investigational drug (under development) or with an investigational device,
E 06. Patients with known ICD lead problem (lead dislodgement)
E 07. 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.
E 08. Recent unstable angina pectoris or myocardial infarction (< 4 weeks),
E 09. History of torsades de pointes,
E 10. Genetic channelopathies including congenital long QT syndrome,
E 11. Wolff-Parkinson-White syndrome,
E 12. 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,
E 13. Incessant sustained VT/VF (VT/VF that recurs promptly despite termination attempts) during the three days preceding randomization.
E 14. Patients with inappropriate (not triggered by VT nor VF) shocks during the month preceding randomization.
E 15. 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.
E 16. Patients treated with oral amiodarone (more than 20 tablets during the 2 months preceding randomization)
E 17. Patients in whom a contraindicated concomitant treatment is mandatory (class I or III antiarrhythmic agents).

Criteria Related to the calibrator arm

E 18. All conditions for which according to the local labelling amiodarone is contraindicated.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Ventricular arrhythmia
MedDRA version: 11.1 Level: LLT Classification code 10047281 Term:

Intervention(s)

Product Name: Celivarone
Product Code: SSR149744C
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Celivarone
CAS Number: 401925-44-8
Current Sponsor code: SSR149744C
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Celivarone
Product Code: SSR149744C
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Celivarone
CAS Number: 401925-44-8
Current Sponsor code: SSR149744C
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Cordarone 200mg comprimés sécables
Product Name: Amiodarone
Product Code: L3428
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Amiodarone
CAS Number: 19774-82-4
Current Sponsor code: L3428
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: The secondary objective are:
•to assess the tolerability of the different dose regimens of celivarone in the selected population
•to document SSR149744 plasma levels during the study.

Main Objective: The primary objective of the study is to assess the efficacy of celivarone for the prevention of Implantable Cardioverter Defibrillator (ICD) interventions or death.

Primary end point(s): VT/VF triggered ICD interventions (shocks or ATPs) or sudden death.

Secondary ID(s)

2008-008412-47-DE

DRI10936