An international study assessing the efficacy of a new drug (S 066913) in paroxysmal atrial fibrillation

• Register: EUCTR
• Last refreshed on: 8 February 2016
• Main ID: EUCTR2014-002333-63-PL
• Date of registration: 25/11/2014
• Prospective Registration: Yes
• Primary sponsor: Institut de Recherches Internationales Servier
• Public title: An international study assessing the efficacy of a new drug (S 066913) in paroxysmal atrial fibrillation
• Scientific title: A randomized, double blind, placebo-controlled, parallel, international multicenter study assessing the efficacy of S066913 in patients with paroxysmal atrial fibrillation Double-blind, International study AssessinG efficacy of S 066913 in paRoxysmal Atrial Fibrillation – IKur inhibitor (DIAGRAF - IKUR) - DIAGRAF-IKur
• Date of first enrolment: 22/01/2015
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002333-63
• 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: no Number of treatment arms in the trial: 4

Countries of recruitment

Australia, Canada, Czech Republic, Denmark, Germany, Netherlands, Poland, Russian Federation, Slovakia, Sweden

Contacts

• Name: Clinical Studies Department
• Affiliation: Institut de Recherches Internationales Servier

• Name: Clinical Studies Department
• Affiliation: Institut de Recherches Internationales Servier

Key inclusion & exclusion criteria

Inclusion criteria:
- Adult patients (except women of childbearing potential) potentially eligible for atrial fibrillation ablation (HRS/EHRA/ECAS 2012; AHA/ACC/HRS 2014 guidelines),
- In sinus rhythm at selection visit ) or sinus rhythm recorded within maximum 7 days since the onset of AF episode in case of ongiong paroxysmal AF),
- With at least one AF episode recorded by ECG , Holter, ICM or any other method to record ECG tracing within 18 months prior to selection visit, and with at least two other AF episodes within 30 days prior to selection visit which can be either typical symptomatic and written down in the medical history or asymptomatic and recorded by ECG, Holter, ICM or any other method to record ECG tracing,
- Eligible for and agreeing to receive ICM implantation following local guidelines and practice, or patients already implanted with an ICM
device of the same type as used in the study
- According to the report extracted from ICM interrogation performed locally by the investigator, AF/AT burden = 1% and = 70% and at least 3 episodes of AF in 4 weeks before inclusion
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 104
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 56

Exclusion criteria:
- AF secondary to a reversible cause,
- Persistent or permanent AF: at selection ; or history of persistent AF with the longest episode lasting more than 30 days; or ablation performed for paroxysmal or persistent AF less than 3 months before selection,
- Patient with more than one anti-arrhythmic drug stopped due to lack of efficacy (rather than intolerance or side effect), provided they were administered at recommended anti-arrhythmic dose,
- Patients previously treated with amiodarone that was stopped because of lack of efficacy, or amiodarone treatment within 3 months prior to selection,
- Corrected QT interval duration (Fridericia?s formula) > 450 ms for male, 470 ms for female,
- High degree atrio-ventricular block (2nd degree or complete),
- Any history of sustained ventricular tachycardia, or resuscitated sudden death,
- Severe chronic heart failure,
- Recent acute coronary syndrome or revascularization
- Unreliable ICM recording
- Sustained ventricular tachycardia, asystole, or sustained bradycardia according to ICM interrogation


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Paroxysmal Atrial Fibrillation
MedDRA version: 18.0 Level: LLT Classification code 10034039 Term: Paroxysmal atrial fibrillation System Organ Class: 100000004849

Intervention(s)

Product Code: S066913
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: S66913
Other descriptive name: S66913
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: S066913
Product Code: S066913
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: S66913
Other descriptive name: S66913
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: S066913
Product Code: S066913
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: S66913
Other descriptive name: S66913
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: Evaluation of the efficacy of 3 doses of S066913 (5mg, 25mg, 100mg) versus placebo administered for 4 weeks on atrial fibrillation and/or atrial tachycardia burden in patients with paroxysmal atrial fibrillation who are potentially eligible for atrial fibrillation ablation and are implanted with insertable cardiac monitoring device.

Secondary Objective: - Evaluation of the safety profile of S066913
- Evaluation of pharmacokinetic profile of S066913

Primary end point(s): - The absolute change from baseline of AF/AT burden

Timepoint(s) of evaluation of this end point: All over the study

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: => Efficacy : All over the study

=> PK measurements : at W004

=> Safety measurements : All over the study

Secondary end point(s): => Efficacy :
- The absolute change from baseline of AF burden
- Mean duration of longest AF/AT episodes
- Mean number of AF/AT episodes
- Incidence of persistent AF
- Percentage of asymptomatic patients (whatever rhythm) and asymptomatic patients (symptoms in sinus rhythm excluded)
- Percentage of patients who have = 30% (= 50%) reduction from baseline in AF/AT burden
- Median ventricular rate in AF
- Quality of life measured by : Canadian Cardiovascular Society (CCS) Severity of Atrial Fibrillation (SAF) scale score and University of Toronto Atrial Fibrillation Severity Scale (AFSS) score

=> Phamacokinetics measurements

=> Safety measurements :
- Adverse events
- ICM recorded arrhytmias outside of AF (Atrial Fibrillation) / AT (Atrial Tachycardia)
- Physical examinations
- ECG
- Laboratory tests

Secondary ID(s)

2014-002333-63-CZ

CL2-066913-002

Source(s) of Monetary Support

ADIR