a study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of hsy244 in participants with atrial fibrillation

Conditions: Atrial Fibrillation

Summary: this was a randomized, placebo-controlled, investigator- and participant-blinded study to evaluate the efficacy, safety, tolerability, and pharmacokinetics (pk) of hsy244 in participants with atrial fibrillation (af), with and without heart failure (hf).

a screening period of up to 3 days (72 hours) was used to assess eligibility. after eligibility was confirmed, patients were randomized to either hsy244 or placebo. prior to study drug administration, pre-dose assessments were completed. after the start of study drug administration, the participant was monitored for cardioversion to sinus rhythm. if a participant was still in af at 90 minutes after the start of study drug administration, direct current cardioversion was planned to be applied at a time deemed appropriate by the investigator.

Eligibility criteria:
key inclusion criteria: * at screening, written informed consent were required to be obtained before any assessment was performed and only participants able to provide written informed consent themselves were included in this study. * hemodynamically stable men and women (either of non-child-bearing potential or child bearing potential with highly effective contraception) between 18 and 80 years of age (inclusive) at screening with a clinical indication for direct current cardioversion of af. * at screening, current episode of af had been ongoing for ≥6 hours and ≤60 days * successful initiation and achievement of therapeutic levels of national guideline and institution-specific anticoagulation therapy as appropriate for the duration of the af episode and risk for the participant. * completion of national guideline and institution-specific imaging evaluation for left atrial thrombi as appropriate for the duration of af episode and risk for the participant. * at screening, participants were required to weigh at least 60 kg to participate in the study and were required to have a body mass index (bmi) within the range of 18 - 45 kg/m\^2. bmi = body weight (kg) / \[height (m)\]\^2 * at screening, vital signs (systolic blood pressure and pulse rate) were assessed in the sitting position. sitting vital signs were required to be within the following ranges (exclusive): * systolic blood pressure between 100-160 mmhg and diastolic blood pressure 60-100 mmhg * pulse rate (ventricular rate) between 60-120 bpm. key exclusion criteria: * women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using highly effective methods of contraception during dosing and for 4 days after stopping of investigational drug. * sexually active males unwilling to use a condom during intercourse while taking investigational drug and for 96 hours after study drug administration. a condom was required for all sexually active male participants to prevent them from fathering a child and to prevent delivery of the investigational drug via seminal fluid to their partner. in addition, male participants could not donate sperm for the time period specified above. * use of any anti-arrhythmic class i or iii drug (including ranolazine \[ranexa\]) within 5 half lives before randomization; including use of amiodarone within 3 months before randomization. * at screening, history of current diagnosis of ecg abnormalities or cardiac rhythm disorders as determined by the investigator's interpretation of the ecg findings indicating a significant risk for participating in the study, such as: * history of torsades de pointes (tdp), any other polymorphic ventricular tachycardia, sustained monomorphic ventricular tachycardia, long qt syndrome, or brugada syndrome. * wolfe-parkinson-white (wpw) syndrome * in the absence of a complete bundle branch block a resting qtcf \>460 msec for men and \>470 msec for women (mean of ≥ 5 consecutive qt intervals) * in the presence of a complete bundle branch block, a prolonged qtcf or jtc that, in the opinion of the investigator, may pose a risk to patient safety * third-degree (complete) heart block, or second-degree mobitz type ii heart block * attempted or unsuccessful cardioversion within 2 weeks prior to randomization. * presence of known severe mitral regurgitation and/or known severely dilated left atrium. * pre-existing or tachycardia-induced moderate to severe cardiac dysfunction (new york heart association class iii and iv). * history within the preceding 3 months prior to randomization of: myocardial infarction, unstable angina, cardiac surgery, or a percutaneous coronary intervention. * history of a confirmed stroke or transient ischemic attack (tia). * history or current diagnosis of any seizure disorder, epilepsy, significant head trauma, or other disorders increasing the risk for seizures. * history or current diagnosis of a major neurologic or psychiatric disorder that, in the opinion of the investigator, poses a risk to patient safety to participate.

Keywords: atrial fibrillation arrhythmia pharmacological cardioversion