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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04582409
• Collaborator: (none)
• Enrollment: 29
• Locations: 12
• Arms: 2
• Anticipated Duration (Months): 23.3
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, tolerability, and pharmacokinetics of HSY244 in participants with atrial fibrillation (AF), with and without heart failure (HF).

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Drug: HSY244; Other: Placebo	Phase 2

Detailed Description

Participants will be randomized and assigned to one of the following 2 treatment arms in a ratio of 5:1:

Arm 1: HSY244 intravenous infusion Arm 2: Placebo intravenous infusion

The study consists of a screening period of up to 3 days and a treatment period of 5 days. After confirming eligibility and pre-dose assessments are completed on Day 1, study administration will occur and participants will be monitored for cardioversion to sinus rhythm. During the treatment period, participants will be evaluated for efficacy, safety, tolerability, and pharmacokinetics.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-controlled, Investigator- and Participant-blinded Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of HSY244 in Participants With Atrial Fibrillation
• Actual Study Start Date: Nov 30, 2020
• Anticipated Primary Completion Date: Nov 8, 2022
• Anticipated Study Completion Date: Nov 8, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HSY244 HSY244 concentrate solution for injection via intravenous infusion	Drug: HSY244; HSY244 concentrate solution for injection via intravenous infusion
Placebo Comparator: Placebo Placebo concentrate solution for injection via intravenous infusion	Other: Placebo; Placebo concentrate solution for injection via intravenous infusion

Outcome Measures

Primary Outcome Measures

1. Conversion to sinus rhythm for at least 1 minute within 90 minutes from the start of study drug administration [1 day]

   Conversion to sinus rhythm will be monitored using a Holter monitoring device through 90 minutes after drug administration.

Secondary Outcome Measures

1. Maximum Observed Serum Concentration (Cmax) [5 days]

   The Cmax is the observed maximum plasma concentration following administration.

2. Time to Reach the Maximum Concentration After Drug Administration (Tmax) [5 days]

   Tmax is the time to reach peak or maximum concentration after drug administration

3. Area under the plasma concentration-time curve (AUClast) [5 days]

   AUClast is the area under the plasma concentration-time curve following drug administration.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Hemodynamically stable men and women between 18 and 80 years of age with a clinical indication for direct current cardioversion of AF

• Current episode of AF has 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

• Participants must weigh at least 60 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 45 kg/m2. BMI = Body weight (kg) / [Height (m)2]

• Written informed consent must be obtained before any assessment is performed and only participants able to provide written informed consent themselves will be included in this study

Key Exclusion Criteria:

• Use of any class I or III anti-arrhythmic medication, or other prohibited medications, within 5 half-lives before randomization, including use of amiodarone within 3 months before randomization

• History or current diagnosis of electrocardiogram (ECG) abnormalities or cardiac rhythm disorders indicating significant risk of safety for participant as determined by the Investigator's interpretation of the ECG findings

• 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 or IV)

• History within the preceding 3 months prior to randomization of either a: myocardial infarction, unstable angina, cardiac surgery, or a percutaneous coronary intervention

• History of confirmed stroke or transient ischemic attack (TIA)

• History or current diagnosis of any seizure disorder or major neurological disorder or major psychiatric disorder

• Sexually active males, including those post-vasectomy, must use a condom during sexual intercourse for at least 96 hours after dosing to prevent delivery of the drug via seminal fluid and should not father a child during this period

• Women must be either of non-childbearing potential or child-bearing potential using highly effective non-hormonal contraception

Other protocol-defined inclusion/exclusion may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Chicago	Illinois	United States	60612
2	Novartis Investigative Site	Boston	Massachusetts	United States	02115
3	Novartis Investigative Site	Boston	Massachusetts	United States	02215
4	Novartis Investigative Site	Lansing	Michigan	United States	48912
5	Novartis Investigative Site	New York	New York	United States	10032
6	Novartis Investigative Site	Hershey	Pennsylvania	United States	17033
7	Novartis Investigative Site	Bad Berka		Germany	99437
8	Novartis Investigative Site	Bad Oeynhausen		Germany	32545
9	Novartis Investigative Site	Dresden		Germany	01307
10	Novartis Investigative Site	Frankfurt		Germany	60590
11	Novartis Investigative Site	Leipzig		Germany	04103
12	Novartis Investigative Site	Ulm		Germany	89081

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04582409
• Other Study ID Numbers: CHSY244X2201; 2020-004327-17
• First Posted: Oct 9, 2020
• Last Update Posted: Jun 7, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: atrial fibrillation; arrhythmia; pharmacological cardioversion
• Additional relevant MeSH terms: Atrial Fibrillation

Study Results

No Results Posted as of Jun 7, 2022