A Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of HSY244 in Participants With Atrial Fibrillation
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Intervention: HSY244; Placebo
Intervention description: HSY244 concentrate solution for injection via intravenous infusion; Placebo concentrate solution for injection via intravenous infusion
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: atrial fibrillation; arrhythmia; pharmacological cardioversion

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).
    

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.