AV Blocks/Heart block is an abnormal heart rhythm where the heart beats too slowly; the electrical signals that tell the heart to contract are partially intermittent (Type 2:1) or slowed (1st and 2nd degree) or blocked (3rd degree) between the upper chambers (atria) and the lower chambers (ventricles). In 2nd degree AV Blocks, electrical impulses are intermittent (type 2:1) or delayed w/ each subsequent heartbeat (Mobitz type I) until a beat fails to reach the ventricles entirely. This type of block often is physiologic and observed in a highly relaxed state & during sleep. In 2nd degree AV Blocks type II, the atria electrical impulses are unable to reach the ventricles, a more serious condition. In 3rd degree AV Blocks (complete heart block), none of the electrical impulses reach either the atria or the ventricles. Patients can experience simultaneously both types of 2nd or 3rd degree AV Blocks without any symptoms.

Safety set: The safety set consisted of all enrolled participants for whom safety information was collected. Two patients of the safety analysis set discontinued the study without having received treatment, but safety information was collected on these two patients.

Number of patients with heart rate below 45 beats bpm in ECG during first dose observation

Safety set: The safety set consisted of all enrolled participants for whom safety information was collected. Two patients of the safety analysis set discontinued the study without having received treatment, but safety information was collected on these two patients.

Number of patients with conduction abnormalities such as QT prolongation, first degree AV block during treatment initiation.

The QT interval is a period between the activation and the regeneration of ventricular contraction. A prolonged QT interval can be a potential marker of cardiac arrhythmias.

Two patients of the safety analysis set discontinued the study without having received treatment, but safety information was collected on these two patients.

The safety set, which consisted of all enrolled participants for whom safety information was collected, was considered for the analysis. Only participants, who had baseline post-dose QTc interval data, were analyzed.

Of the 6998 patients, 6844 patients had complete baseline post-dose QTc interval data.

The number of participants with bradyarrhythmic electrocardiogram (ECG) events was assessed. Bradyarrhythmic ECG events are defined as QTc Fridericia time > 450 ms for males and > 470 ms for females.

Safety set: The safety set consisted of all enrolled participants for whom safety information was collected. Two patients of the safety analysis set discontinued the study without having received treatment, but safety information was collected on these two patients.

The number of participants with the occurrence of subsequent cardiac adverse events (AEs) and serious cardiac AEs during study was assessed. Cardiac events were defined as the following Medical Dictionary for Regulatory Activities (MedDRA) preferred terms: angina pectoris, chest discomfort, dizziness, dyspnoea, dyspnoea exertional, fatigue, palpitations, syncope, vertigo, vertigo positional and vision blurred.

Safety set: The safety set consisted of all enrolled participants for whom safety information was collected. Two patients of the safety analysis set discontinued the study without having received treatment, but safety information was collected on these two patients.