Atrial Fibrillation MedDRA version: 12.1 Level: LLT Classification code 10003658 Term: Atrial fibrillation
Conditions
Interventions
Product Name: K201
Product Code: K201
Pharmaceutical Form: Tablet
CAS Number: 1038410-88-6
Current Sponsor code: K201
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number
Sponsors
Sequel Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Comprehend and sign a written informed consent form, (per local and national regulations, as applicable) 2. Age of 18 years or more. 3. Women must not be pregnant, be non-nursing and if pre-menopausal, must be using an effective form of birth control from time of screening until the two week follow-up visit after the last dose of medication. Methods of birth control considered to be effective are hormonal anticonception; birth control pill, implant, transdermal depot adhesive, vaginal ring or depot injection), an intrauterine device (IUD), or sterilization. Men should be advised not to conceive a child and are advised to use an effective form of birth control from admission until the two week follow-up visit after the last dose of study medication 4. Have symptomatic AF that has been sustained for greater than 3 days (72 hours) and less than 180 days (6 months) duration and is clinically indicated for cardioversion; subjects may have a mix of AF and atrial flutter if AF is predominant and was the presenting arrhythmia. 5. Have adequate anticoagulant therapy for cardioversion in accordance standard of practice as recommended by ACC/AHA/ESC guidelines 8 or with local clinical practice (e.g. TEE algorithm); 6. Be hemodynamically stable (90 mmHg =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. At screening, have known prolonged QT syndrome, familial Long QT syndrome, QTcF interval of >500 msec as measured on a 12-lead ECG while in AF; previous history of Torsade de Pointes, ventricular fibrillation, or sustained ventricular tachycardia (VT); After DC cardioversion and while in sinus rhythm, QTcF >440/450 ms for males/females, respectively. 2. Have a QRS >0.130 sec. 3. Previous episodes of second or third-degree atrioventricular block. 4. Last DC cardioversion attempt occurred within 3 months and was unsuccessful (including IRAF); or any prior ablation for AF. 5. Have persistent bradycardia with ventricular rate below 50 beats/min that in the opinion of the investigator is clinically significant, sick-sinus syndrome or pacemaker (including CRT, AICD). Have persistent tachycardia greater than 110 beats/min. 6. Have clinically significant moderate or severe valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis. 7. Have NYHA Class III or Class IV heart failure (HF) at screening or admission, have been hospitalized with HF or new diagnosis of HF in the previous 6 months; any change in HF medications within 2 months; NT-proBNP > 47 pmol/L; EF3X ULN), metabolic, renal (i.e. eGFR < 30mL/min), gastrointestinal, central nervous system (i.e. stroke or TIA within past 6 months) or psychiatric disease (e.g. drug addiction or alcohol dependence), end-stage disease states, or any other disease that in the opinion of the investigator could interfere with the conduct or validity of the study or compromise subject safety. 9. Have known concurrent temporary secondary causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, pneumonia, hypoxemia (oxygen saturation < 90% on room air), acute pericarditis, or myocarditis. 10. Hypokalemia (K+ should be corrected prior to dosing). 11. Have clinical evidence of digoxin toxicity. 12. Have received a Class I or Class III antiarrhythmic agent (including sotalol) within 5 half-lives of randomization or amiodarone or dronedarone within 4 weeks. 13. Have received treatment with other drugs known to prolong the QT interval within 5 half-lives, including, certain antidepressants (e.g. tricyclic antidepressants), certain antihistaminics (e.g. terfenadine, astemizole), certain antiinfectives (e.g. erythromycin), certain antipsychotics (e.g. haloperidol, pimozide, thioridazine, ziprasidone); certain cardiovascular non-antiarrhythmics (e.g. bepridil), certain gastro-intestinal agents (e.g. cisapride). 14. Have any other surgical or medical condition that, in the judgment of the clinical Investigator might warrant exclusion or be contraindicated for safety reasons. 15. Be concurrently participating in another investigational drug study or have received an investigational drug within 30 days or 5 half-lives prior to screening. 16. Be unable to communicate well with the Investigator and to comply with the requirements of the entire study. 17.Have received potent CYP2D6 or CYP3A inhibitors within 5 half-lives. Potent CYP2D6 include bupropion, fluoxetine, paroxetine, cinacalcet and quinidine. Potent CYP3A inhibitors include indinavir, nelfinavir, ritonavir, saquinavir, clarithr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety, efficacy, and tolerability of 3 doses of K201 administered for 28 days in subjects with recent DC cardioversion to sinus rhythm from sustained symptomatic atrial fibrillation (AF duration >3 days and 30 consecutive beats of AFib/flutter origin) 6. Change in AF symptoms as assessed by the AF symptom checklist. 7. Change in CCS-Severity of AF scale 8. Days dead or in AF during 28 days 9. Days dead or hospitalized during the 28 days 10. Proportion of subjects with CV mortality or AF re-admission to day 28 Safety and tolerability in randomised subjects will be continuously evaluated based on Adverse Events/Serious Adverse Events (AE/SAE) reporting and monitoring of laboratory evaluations, ECG and vital signs. Safety parameters will include: • Physical examinations, medical history, vital signs, ECG, standard laboratory test panels, and monitoring of adverse events. • ECGs assessments by 12-lead ECGs recorded at scheduled clinic visits. Holter/TTEM data will be read by an independent core lab. • Safety variables of particular interest include the hemodynamic parameters of blood pressure and heart rate as well as ECG parameters and analyses of QT, QTcB, QTcF, the incidence of Torsade des pointes, and other ventricular arrhythmias, including bradyarrhythmias. | — |
Countries
Sweden
Outcome results
None listed