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 S066913 in paRoxysmal Atrial Fibrillation -IKur inhibitor (DIAGRAF - IKUR)

AF is the most common sustained cardiac arrhythmia (33.5 million people
worldwide, near 5 million new cases each year), and its prevalence will
increase with the aging population. AF is associated with an increased risk of
stroke incidence and mortality. The disease is progressive and can progress to
permanent AF. Currently available AAD's are moderately effective in restoring
and maintinain sinus rhythm. Moreover, they can produce serious adverse effects
and although efficient in reducing stroke risk, are not associated with
improvement in mortality. While effective, catheter ablation conveys a relevant
risk of major complications. S066913 potently and selectively inhibits the IKur
channel in the atria, by increasing the AERP (atrial effective refractory
period). Aymptomatic atrial tachyarrhythmias occur frequently and the stroke
risk is at least as high as it is for symptomatic patients. As correlation of
symptoms with the AF episodes is limited, it is not possible to rely on
symptoms to detect AF or to measure the effect of a rhythm control treatment.
Conventional methods used for PAF detection have limited sensitivity due to the
infrequent measurements. Insertable continuous monitoring (ICM) devices have
been equipped with AF detection and measurement capabilities and can be
subcutaneously inserted under local anaesthesia. The use of these highly
sensitive and specific ICM's has demonstrated that continuous monitoring was
much more accurate than conventional monitoring to detect AF recurrences post
ablation.

The aim of this study is to evaluate the efficacy of three doses of S 066913 (5
mg, 25 mg and 100 mg o.d.) versus placebo administered for 4 weeks on atrial
fibrillation and/or atrial tachycardia burden (AF/AT burden) in patients with
paroxysmal atrial fibrillation (PAF) who are potentially eligible for atrial
fibrillation (AF) ablation and are implanted with insertable cardiac monitoring
(ICM) device.
The safety and pharmacokinetic profile of S 066913 will also be evaluated.

Target population: patients with PAF who are potentially eligible for AF
ablation.
Randomized, double blind, placebo-controlled, parallel, international
multicenter study to evaluate the efficacy of S 066913 on AF/AT burden.

During the selection visit or during the following days, the ICM will be
implanted subcutaneously under local anaesthesia. The ICM can remain implanted
after the study until it's breakdown.
oral administration of S066193 or placebo

ICM implantation may be associated with potential risks and discomforts. A
little bleeding during the procedure and bruising over the ICM are common and
usually of no consequence. There is about 2% (2 in every 100 patients)
probability of the ICM causing potential risks. They include, but are not
limited to: *Infection at the implant site. To minimise the risk, antibiotics
can be used before and after the procedure.
*A hematoma over the ICM. Occasionally this needs to be drained.
*Pain at the implant site.
*Movement of the ICM from its initial position or coming through the skin.
*Rejection of the ICM by the body, which may involve symptoms such as swelling,
redness, or other irritation at, or near, the implant site.
Taking blood samples may cause some discomfort, bruising or bleeding from the
site of sampling and may cause a blood clot or bruising.