A Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of HSY244 in Participants With Atrial Fibrillation

Novartis

Status and phase: Terminated; Phase 2

Conditions: Atrial Fibrillation

Treatments: Other: Placebo; Drug: HSY244

Study type: Interventional

Funder types: Industry

Identifiers

NCT04582409

CHSY244X2201

2020-004327-17 (EudraCT Number)

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 13 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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13 participants in 2 patient groups, including a placebo group

HSY244

Experimental group

Description:

HSY244 150 mg concentrate solution for injection via intravenous infusion

Treatment:

Drug: HSY244

Placebo

Placebo Comparator group

Description:

Placebo concentrate solution for injection via intravenous infusion

Treatment:

Other: Placebo