E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
An abnormal and irregular heart rhythm in which electrical signals are generated chaotically throughout the upper chambers of the heart. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003658 |
E.1.2 | Term | Atrial fibrillation |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the efficacy of HSY244 to restore sinus rhythm in participants with Atrial Fibrillation |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety, tolerability, and pharmacokinetics of HSY244 in participants with Atrial Fibrillation |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent must be obtained before any assessment is performed. Only participants able to provide written informed consent themselves will be included in this study. 2. Hemodynamically stable men and women between 18 and 75 years of age inclusive with a clinical indication for direct current cardioversion of Atrial Fibrillation. 3. Current episode of AF has been ongoing for ≥6 hours and ≤30 days 4. Successful initiation and achievement of therapeutic levels of national guideline and institution-specific anticoagulation therapy as appropriate for the duration of the Atrial Fibrillation episode and risk for the participant. 5. Completion of national guideline and institution-specific imaging evaluation for left atrial thrombi as appropriate for the duration of Atrial Fibrillation episode and risk for the participant. 6. 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 - 35 kg/m2. BMI = Body weight (kg) / [Height (m)]2 7. At screening, vital signs (systolic blood pressure and pulse rate) will be assessed in the sitting position. Sitting vital signs should 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 8. Able to communicate well with the investigator, to understand and comply with the requirements of the study.
"Other inclusion criteria may apply" |
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E.4 | Principal exclusion criteria |
1. Women of child-bearing potential unless they are using highly effective methods of contraception 2. Pregnant or nursing (lactating) women. 3. Sexually active males unwilling to use a condom during intercourse 4. Use of a QT prolonging drug within 5 half-lives before randomization 5. History or current diagnosis of ECG abnormalities or cardiac rhythm disorders 6. Clinically significant sinus node dysfunction and/or presence of a permanent pacemaker. 7. Attempted or unsuccessful cardioversion within 2 weeks prior to randomization 8. History of 2 or more ablation procedures for Atrial Fibrillation 9. Presence of a left atrial thrombus that may pose a risk of embolization with cardioversion 10. Presence of known severe mitral regurgitation and/or known severely dilated left atrium. 11. Pre-existing or tachycardia-induced moderate to severe cardiac dysfunction (New York Heart Association Class III and IV). 12. History within the preceding 3 months prior to randomization of: myocardial infarction, unstable angina, cardiac surgery, or a percutaneous coronary intervention. 13. History of a confirmed stroke or transient ischemic attack (TIA). 14. History or current diagnosis of any seizure disorder, epilepsy, significant head trauma, or other disorders increasing the risk for seizures. 15. 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. 16. Moderately or greater impaired renal function 17. Liver disease or liver injury 18. Donation or loss of 450 mL or more of blood within eight weeks prior to randomization, or longer if required by local regulation. 19. Have any other conditions which, in the opinion of the Investigator, would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study 20. Significant illness and/or infection which has not resolved within two (2) weeks prior to initial dosing.
"Other exclusion criteria may apply" |
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E.5 End points |
E.5.1 | Primary end point(s) |
Conversion to sinus rhythm for at least 1 minute within 90 minutes from the start of study drug administration |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
over 90 minutes from the start of study drug administration |
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E.5.2 | Secondary end point(s) |
1. safety and tolerability of HSY244 as measured by adverse events, vital signs, ECG parameters, and laboratory assessments of blood and urine.
2. Pharmacokinetics of HSY244 as measured by plasma AUClast, Cmax, and Tmax |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
As outline in the assessment schedule in the protocol at screening, Day 1, Day 2 and Day 4 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 9 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |