A Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of PKN605 in Participants With Atrial Fibrillation

Inclusion Criteria

• Inclusions at Screening

• Signed informed consent must be obtained prior to participation in the study
• Male and female participants ≥ 18 years of age
• History of at least 2 episodes of AF (atrial fibrillation or atrial flutter), at least one episode must be atrial fibrillation
• At least 1 of the AF episodes specified in inclusion #3 must be within the last 12 months (or during screening) and documented by 12-lead ECG, Holter, or any other ECG recording method, as confirmed by the Investigator
• One or more of the following:
• AFB of 1% or higher on a local ambulatory Holter, mobile cardiac telemetry, ECG patch monitor, or other ambulatory electrocardiographic monitor within the last 12 months
• CHA2DS2-VASc score of 2 or higher in males, 3 or higher in females (1 point for congestive heart failure, hypertension, age 65-74 years, diabetes, vascular disease, female sex; 2 points for age 75 years or older, prior stroke or transient ischemic attack)
• Stable heart failure or with New York Heart Association class I or II symptoms
• NT-proBNP level of 300 pg/mL or higher on a local lab test within the last 12 months

• On guideline-directed stroke prevention treatment, as confirmed by the Investigator
• Participants must have a body mass index (BMI) ≥ 18 kg/m2. BMI is calculated as body weight (kg) divided by height (m) squared
• Inclusions at Day 1

• Sinus rhythm at Baseline documented by 12-lead ECG (participants with persistent AF should be cardioverted at least 12 hours before randomization)

Exclusion Criteria

-Exclusions at Screening

• Permanent AF
• Ongoing reversible causes of AF (e.g., hyperthyroidism, myocarditis, acute alcohol, sepsis- or infection related AF, surgery-related AF, pulmonary embolism)
• Ongoing use of antiarrhythmic therapy (Vaughan Williams class I or III anti-arrhythmic therapy must be discontinued at least 7 days before Screening phase ECG patch monitor; amiodarone must be discontinued at least 6 weeks before Screening phase ECG patch monitor)
• History of an AF ablation procedure without a recurrence of AF at least 2 or more months after the ablation.
• Implanted pacemaker, defibrillator, or cardiac monitor
• Infiltrative (e.g., amyloidosis, sarcoidosis) or hypertrophic cardiomyopathy
• Left ventricular ejection fraction of 40% or less documented within the last 12 months, or during Screening. If multiple LVEF measurements are recorded within the last 12 months, the most recent LVEF measurement should be used
• Current decompensated heart failure or hospitalization for heart failure within 3 months prior to Screening