A Study Evaluating the Efficacy and Safety of AP30663 for Cardioversion in Participants With Atrial Fibrillation (AF)

Percentage of Participants With Sinus Rhythm (SR) at 3 Hours, 24 Hours and Day 30 After Start of Infusion

The 12-lead Holter monitoring equipment was used to monitor heart rate and its rhythm. ECG was performed in a standardized manner that the participant had rested in the semi-supine position for at least 5 minutes. Percentage of participants in SR was assessed from Holter ECGs at 3 hours, 24 hours and Day 30 after start of infusion. Percentages were based on "number of participants in SR at 3 hours, 24 hours and Day 30 after start of infusion" divided by "total number of participants" \*100 in each treatment group.

Time frame: At 3 hours, 24 hours and Day 30 after start of Infusion (Day 1)

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. TEAEs are defined as any AE occurring or worsening on or after the first dose of study medication. A serious adverse event (SAE) is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. TEAEs include both serious and non-serious adverse events.

Time frame: From start of infusion (Day 1) up to follow-up (Day 35)

Changes From Baseline in Fridericia's Correction of QT Interval (ΔQTcF) Interval Data Over Time

QTcF was assessed based on 12-lead Holter monitoring equipment. Triplicate ECGs were extracted at the same time points as PK sampling and were read in a semi-automated manner by a blinded cardiologist. The participant rested in the semi-supine position for at least 5 minutes at ECG extraction timepoints. Change from baseline was estimated based on a linear mixed-effects model: ΔQTcF = Time + Treatment + Time\*Treatment + Baseline QTcF.

Time frame: Baseline, 15 minutes, 45 minutes, 2 hours, 8 hours and 24 hours post-dose

Maximum Observed Peak Plasma Concentration (Cmax) of AP30663

Cmax was defined as the maximum observed peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Blood samples were collected at indicated timepoints. Pharmacokinetics (PK) was conducted using standard noncompartmental method.

Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion

Time to Reach Peak Plasma Concentration (Tmax) of AP30663

Tmax was directly determined from concentration time data. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.

Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion

Terminal Half Life of (T1/2) of AP30663

T1/2 was calculated as loge (2) per elimination rate constant (kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.

Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion

Area Under the Concentration Time Curve From Pre-dose Concentration up to 30 Minutes (AUC0-0.5) of AP30663

AUC0-0.5 was defined as area under the concentration time curve from pre-dose concentration up to 30 minutes. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.

Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30 minutes post-infusion

Area Under the Concentration Time Curve up to the Last Measurable Concentration (AUC0-t) of AP30663

AUC0-t was defined as area under the concentration-time curve from time zero to time of last measurable concentration. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.

Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion

Area Under the Concentration-Time Curve From Pre-dose (Zero) Through Concentration to Infinity (AUC0-inf) of AP30663

AUC0-inf was defined as area under the concentration time curve from pre-dose through concentration to infinity (extrapolated), calculated as AUC0-t + Ct/Kel, where Ct is the last observed non-zero concentration. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.

Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion

Elimination Rate Constant (Kel) of AP30663

Kel represents the fraction of drug eliminated per unit of time. Elimination rate constant was calculated using linear regression on the terminal portion of the log-linear concentration versus time curve. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.

Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion