Phase 2 Study of Oral K201 for Prevention of AF Recurrence (ARCTIC-AF)

• time to first documented recurrence of symptomatic AF [ Time Frame: 28 days ] [ Designated as safety issue: No ]
• time to first documented recurrence of symptomatic or asymptomatic AF [ Time Frame: 28 days ] [ Designated as safety issue: No ]
• proportion of subjects in sinus rhythm [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
• number of AF beats [ Time Frame: 10 days ] [ Designated as safety issue: No ]
• time in AF [ Time Frame: 10 days ] [ Designated as safety issue: No ]
• safety assessments: vital signs, laboratory assays, ECG parameters, physical exams, frequency of adverse events [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]

To evaluate the safety, efficacy, and tolerability of 3 doses of K201 (oral) administered for up to 28 days in subjects with recent DC cardioversion to sinus rhythm from sustained symptomatic atrial fibrillation (AF duration >3 days and <6 months).

• Drug: K201 Tablet
  oral tablet, x28 days
• Drug: Placebo Tablet
  oral tablet, x28 days

• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo Tablet
• Experimental: Dose 1
  K201
  Intervention: Drug: K201 Tablet
• Experimental: Dose 2
  K201
  Intervention: Drug: K201 Tablet
• Experimental: Dose 3
  K201
  Intervention: Drug: K201 Tablet

Inclusion Criteria:

• Symptomatic AF (sustained >3 days and <6 months) and clinically indicated for cardioversion;
• Adequate anticoagulant therapy for cardioversion in accordance with standard practice as recommended by ACC/AHA/ESC guidelines or with local clinical practice;
• Hemodynamically stable (90 mmHg < systolic blood pressure < 190 mmHg)at screening and on Day 1;

Exclusion Criteria:

• Known prolonged QT syndrome or QTc interval of >0.500 sec at screening; familial long QT syndrome; previous Torsade de Pointes; ventricular fibrillation; or sustained ventricular tachycardia (VT);
• QRS >0.130 sec;
• Previous episodes of second- or third-degree atrioventricular block;
• Unsuccessful DC cardioversion attempt within 3 months; prior ablation for AF;
• Persistent bradycardia with ventricular rate below 50 beats/min, sick-sinus syndrome or pacemaker (including CRT, AICD);
• Myocardial infarction (MI), cardiac surgery, angioplasty, unstable angina or acute coronary syndrome within 30 days prior to entry into the study;
• NYHA Class III or Class IV heart failure (HF) at screening or admission, or hospitalized for HF in previous 6 months;
• Known concurrent temporary secondary causes of AF;
• Received a Class I or Class III antiarrhythmic agent (including sotalol) within 5 half-lives of randomization or amiodarone or dronedarone within 4 weeks;
• Received treatment with other drugs known to prolong the QT interval within 5 half-lives.