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

NCT ID: NCT04582409

Last Updated: 2024-06-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-30
• Study Completion Date: 2022-07-11

Brief 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).

Detailed 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.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

HSY244

HSY244 150 mg concentrate solution for injection via intravenous infusion

Group Type: EXPERIMENTAL

HSY244

Intervention Type: DRUG

HSY244 concentrate solution for injection via intravenous infusion

Placebo

Placebo concentrate solution for injection via intravenous infusion

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo concentrate solution for injection via intravenous infusion

Interventions

HSY244

HSY244 concentrate solution for injection via intravenous infusion

Intervention Type: DRUG

Placebo

Placebo concentrate solution for injection via intravenous infusion

Intervention Type: OTHER

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Boston, Massachusetts, United States

Novartis Investigative Site

Lansing, Michigan, United States

Novartis Investigative Site

Bad Oeynhausen, , Germany

Novartis Investigative Site

Frankfurt, , Germany

Countries

United States; Germany

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=18069

Results for CHSY244X2201 that is getting linked from the Novartis Clinical Trials Website

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1719

Patient Lay Trial Summary

Other Identifiers

2020-004327-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CHSY244X2201

Identifier Type: -

Identifier Source: org_study_id