Trial Outcomes & Findings for A Study Evaluating the Efficacy and Safety of AP30663 for Cardioversion in Participants With Atrial Fibrillation (AF) (NCT NCT04571385)

Results Overview

The 12-lead Holter monitoring equipment was used to monitor heart rate and its rhythm. Electrocardiogram (ECG) was performed in a standardized manner after the participant had rested in the semi-supine position for at least 5 minutes. Conversion from AF to normal sinus rhythm within 90 minutes from start of infusion was determined by the investigator and documented with a rhythm strip confirming conversion. Percentages were based on "number of participants converted from atrial fibrillation and absence of recurrence of AF within 1 minute of conversion" divided by "total number of participants" \*100 in each treatment group. Analysis was performed based on Bayesian model.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

66 participants

Primary outcome timeframe

Within 90 minutes from the start of infusion (Day 1)

Results posted on

2024-05-06

Participant Flow

The study was conducted at 8 active sites in 2 countries (Denmark and Hungary) from 09 September 2019 to 23 January 2023.

A total of 66 participants were enrolled, of which 63 participants received the study treatment in 2 parts. Part 1 consists of Placebo and AP30663 (3 milligrams per kilogram \[mg/kg\]) and part 2 consist of Placebo and AP30663 (5 mg/kg). As per the planned statistical analysis, placebo arms with similar dosing strategies in Part 1 and Part 2 were combined to be reported as a pooled placebo arm.

Participant milestones

Participant milestones
Measure	Part 1 and 2: Pooled Placebo Participants received a single intravenous (IV) infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Overall Study STARTED	27	16	23
Overall Study Part 1	16	16	0
Overall Study Part 2	11	0	23
Overall Study Full Analysis Set (FAS)	25	12	22
Overall Study Safety Set	26	15	22
Overall Study Pharmacokinetic (PK) Set	0	15	22
Overall Study Treated	26	15	22
Overall Study COMPLETED	26	15	22
Overall Study NOT COMPLETED	1	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1 and 2: Pooled Placebo Participants received a single intravenous (IV) infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Overall Study Participant non-compliance	1	0	0
Overall Study Converted to Sinus Rhythm (SR) before the infusion	0	1	0
Overall Study Screen failure	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1 and 2: Pooled Placebo n=26 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=15 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg n=22 Participants Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.	Total n=63 Participants Total of all reporting groups
Age, Continuous	64.3 years STANDARD_DEVIATION 9.23 • n=5 Participants	65.4 years STANDARD_DEVIATION 8.48 • n=7 Participants	65.5 years STANDARD_DEVIATION 10.38 • n=5 Participants	65.0 years STANDARD_DEVIATION 9.35 • n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	18 Participants n=4 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	12 Participants n=7 Participants	15 Participants n=5 Participants	45 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	15 Participants n=7 Participants	22 Participants n=5 Participants	63 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Within 90 minutes from the start of infusion (Day 1)

Population: Full Analysis Set included all randomized participants who were administered double-blind study treatment and had an evaluable AF conversion status within 90 minutes from the start of infusion.

The 12-lead Holter monitoring equipment was used to monitor heart rate and its rhythm. Electrocardiogram (ECG) was performed in a standardized manner after the participant had rested in the semi-supine position for at least 5 minutes. Conversion from AF to normal sinus rhythm within 90 minutes from start of infusion was determined by the investigator and documented with a rhythm strip confirming conversion. Percentages were based on "number of participants converted from atrial fibrillation and absence of recurrence of AF within 1 minute of conversion" divided by "total number of participants" \*100 in each treatment group. Analysis was performed based on Bayesian model.

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo n=25 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=12 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg n=22 Participants Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Percentage of Participants Who Converted From Atrial Fibrillation (AF) Within 90 Minutes From Start of Infusion and Subsequently Had no AF Recurrence Within 1 Minute of Conversion From AF	0 Percentage of participants	41.7 Percentage of participants	54.5 Percentage of participants

SECONDARY outcome

Timeframe: From start of infusion (Day 1) up to Day 2

Population: Full Analysis Set included all randomized participants who were administered double-blind study treatment and had an evaluable AF conversion status within 90 minutes from the start of infusion. Here, "overall number of participants analyzed" signifies those participants were evaluable for this outcome measure. No participant had conversion from AF to normal rhythm in placebo arm.

The 12-lead Holter monitoring equipment was used to monitor heart rate and its rhythm. ECG was performed in a standardized manner after the participant had rested in the semi-supine position for at least 5 minutes. Time to conversion (in minutes) was calculated by time of conversion or censoring minus time of start of infusion.

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=5 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg n=12 Participants Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Time to Conversion From Atrial Fibrillation From Start of Infusion	—	42.0 Minutes Interval 24.0 to 81.0	35.0 Minutes Interval 19.0 to 89.0

SECONDARY outcome

Timeframe: Within 5 minutes after cardioversion (Day 1)

Population: Full Analysis Set included all randomized participants who were administered double-blind study treatment and had an evaluable AF conversion status within 90 minutes from the 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 after the participant had rested in the semi-supine position for at least 5 minutes. Participants with relapse of AF within 5 minutes following pharmacological or DC cardioversion was presented by treatment and analyzed using a logistic regression model. Percentages were based on "number of participants with relapse of AF within 5 minutes after Pharmacological or DC cardioversion" divided by "total number of participants" \*100 in each treatment group.

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo n=25 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=12 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg n=22 Participants Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Percentage of Participants With Relapse of AF Within 5 Minutes (IRAF) After Pharmacological or Direct Current (DC) Cardioversion	4.0 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

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

Population: Full Analysis Set included all randomized participants who were administered double-blind study treatment and had an evaluable AF conversion status within 90 minutes from the start of infusion. Here, "overall number of participants analyzed" signifies those participants were evaluable for this outcome and "number analyzed" signifies participants at specific timepoints.

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.

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo n=25 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=11 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg n=21 Participants Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Percentage of Participants With Sinus Rhythm (SR) at 3 Hours, 24 Hours and Day 30 After Start of Infusion Sinus Rhythm at 3 hours	84.0 Percentage of participants	100.0 Percentage of participants	95.2 Percentage of participants
Percentage of Participants With Sinus Rhythm (SR) at 3 Hours, 24 Hours and Day 30 After Start of Infusion Sinus Rhythm at 24 hours	76.0 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants
Percentage of Participants With Sinus Rhythm (SR) at 3 Hours, 24 Hours and Day 30 After Start of Infusion Sinus Rhythm at Day 30	64.0 Percentage of participants	90.0 Percentage of participants	71.4 Percentage of participants

SECONDARY outcome

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

Population: Safety set included all randomized participants who were administered double-blind study treatment. Participants analyzed according to the treatment received.

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.

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo n=26 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=15 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg n=22 Participants Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with TEAEs	13 Participants	4 Participants	11 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with Serious TEAEs	4 Participants	0 Participants	0 Participants

SECONDARY outcome

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

Population: All randomized participants who were administered double-blind study treatment and with measurements at baseline as well as on-treatment with at least 1 post-dose time point with a valid ΔQTcF value. Participants were analyzed according to the treatment received. Here, "number analyzed" signifies those participants were evaluable at specific timepoints.

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.

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo n=26 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=15 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg n=22 Participants Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Changes From Baseline in Fridericia's Correction of QT Interval (ΔQTcF) Interval Data Over Time Change at 15 minutes post-dose	1.9 Millisecond Standard Error 3.21	11.7 Millisecond Standard Error 4.26	21.2 Millisecond Standard Error 3.49
Changes From Baseline in Fridericia's Correction of QT Interval (ΔQTcF) Interval Data Over Time Change at 45 minutes post-dose	1.0 Millisecond Standard Error 3.21	19.4 Millisecond Standard Error 4.26	37.7 Millisecond Standard Error 3.53
Changes From Baseline in Fridericia's Correction of QT Interval (ΔQTcF) Interval Data Over Time Change at 2 hours post-dose	6.2 Millisecond Standard Error 3.93	23.0 Millisecond Standard Error 4.26	—
Changes From Baseline in Fridericia's Correction of QT Interval (ΔQTcF) Interval Data Over Time Change at 8 hours post-dose	11.5 Millisecond Standard Error 3.29	13.6 Millisecond Standard Error 4.34	17.2 Millisecond Standard Error 3.59
Changes From Baseline in Fridericia's Correction of QT Interval (ΔQTcF) Interval Data Over Time Change at 24 hours post-dose	10.3 Millisecond Standard Error 3.74	14.9 Millisecond Standard Error 4.67	13.1 Millisecond Standard Error 4.53

SECONDARY outcome

Timeframe: 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

Population: The PK Set included all participants in the Safety Set who had at least one evaluable post-baseline drug concentration value.

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.

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo n=15 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=22 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Maximum Observed Peak Plasma Concentration (Cmax) of AP30663	7606.065 Micrograms per liter Geometric Coefficient of Variation 31.5	10281.754 Micrograms per liter Geometric Coefficient of Variation 30.9	—

SECONDARY outcome

Timeframe: 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

Population: The PK Set included all participants in the Safety Set who had at least one evaluable post-baseline drug concentration value.

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

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo n=15 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=22 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Time to Reach Peak Plasma Concentration (Tmax) of AP30663	0.4170 Hours Interval 0.25 to 0.5	0.4170 Hours Interval 0.25 to 1.0	—

SECONDARY outcome

Timeframe: 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

Population: The PK Set included all participants in the Safety Set who had at least one evaluable post-baseline drug concentration value. Here, "overall number of participants analyzed" signifies those participants were evaluable for this outcome.

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.

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo n=14 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=22 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Terminal Half Life of (T1/2) of AP30663	5.363 Hours Interval 2.6 to 8.39	5.620 Hours Interval 4.35 to 8.74	—

SECONDARY outcome

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

Population: The PK Set included all participants in the safety set who had at least one evaluable post-baseline drug concentration value.

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.

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo n=15 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=22 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Area Under the Concentration Time Curve From Pre-dose Concentration up to 30 Minutes (AUC0-0.5) of AP30663	2568.175 Hours*micrograms per liter Geometric Coefficient of Variation 41.2	3446.078 Hours*micrograms per liter Geometric Coefficient of Variation 79.1	—

SECONDARY outcome

Timeframe: 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

Population: The PK Set included all participants in the safety set who had at least one evaluable post-baseline drug concentration value.

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.

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo n=15 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=22 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Area Under the Concentration Time Curve up to the Last Measurable Concentration (AUC0-t) of AP30663	19328.384 Hours*micrograms per liter Geometric Coefficient of Variation 44.0	29587.109 Hours*micrograms per liter Geometric Coefficient of Variation 31.4	—

SECONDARY outcome

Timeframe: 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

Population: The PK Set included all participants in the safety set who had at least one evaluable post-baseline drug concentration value. Here, "overall number of participants analyzed" signifies those participants were evaluable for this outcome.

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.

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo n=14 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=22 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Area Under the Concentration-Time Curve From Pre-dose (Zero) Through Concentration to Infinity (AUC0-inf) of AP30663	21623.095 Hours*micrograms per liter Geometric Coefficient of Variation 43.4	31448.932 Hours*micrograms per liter Geometric Coefficient of Variation 33.3	—

SECONDARY outcome

Timeframe: 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

Population: The PK Set included all participants in the safety set who had at least one evaluable post-baseline drug concentration value. Here, "overall number of participants analyzed" signifies those participants were evaluable for this outcome.

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.

Outcome measures

Outcome measures
Measure	Part 1 and 2: Pooled Placebo n=14 Participants Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=22 Participants Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Elimination Rate Constant (Kel) of AP30663	0.13092 Per hour Geometric Coefficient of Variation 31.4	0.11817 Per hour Geometric Coefficient of Variation 18.6	—

Adverse Events

Part 1 and 2: Pooled Placebo

Serious events: 4 serious events

Other events: 13 other events

Deaths: 0 deaths

Part 1: AP30663 3mg/kg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part 2: AP30663 5mg/kg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1 and 2: Pooled Placebo n=26 participants at risk Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=15 participants at risk Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg n=22 participants at risk Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Cardiac disorders Atrial fibrillation	15.4% 4/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.

Other adverse events

Additional Information

Birgitte Vestbjerg

Acesion Pharma

Phone: +45 20772575

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Part 1 and 2: Pooled Placebo n=26 participants at risk Participants received a single IV infusion of AP30663 matched placebo for 30 minutes on Day 1 in both Part 1 and 2.	Part 1: AP30663 3mg/kg n=15 participants at risk Participants received a single IV infusion of AP30663 3mg/kg for 30 minutes on Day 1 in Part 1.	Part 2: AP30663 5mg/kg n=22 participants at risk Participants received a single IV infusion of AP30663 5mg/kg for 30 minutes on Day 1 in Part 2.
Cardiac disorders Atrial fibrillation	26.9% 7/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	6.7% 1/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	31.8% 7/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Cardiac disorders Atrial flutter	3.8% 1/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	13.6% 3/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Cardiac disorders Atrioventricular block first degree	3.8% 1/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	13.3% 2/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Cardiac disorders Bundle branch block left	0.00% 0/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	4.5% 1/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Cardiac disorders Bundle branch block right	0.00% 0/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	4.5% 1/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Cardiac disorders Left ventricular failure	0.00% 0/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	4.5% 1/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Cardiac disorders Supraventricular tachycardia	3.8% 1/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Vascular disorders Hypotension	0.00% 0/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	6.7% 1/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	4.5% 1/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Vascular disorders Phlebitis	7.7% 2/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Vascular disorders Hypertension	0.00% 0/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	6.7% 1/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Investigations Blood bilirubin increased	0.00% 0/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	4.5% 1/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Investigations Electrocardiogram QT prolonged	0.00% 0/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	6.7% 1/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	4.5% 1/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Metabolism and nutrition disorders Hypokalaemia	3.8% 1/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Renal and urinary disorders Haematuria	0.00% 0/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	9.1% 2/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Nervous system disorders Dizziness postural	0.00% 0/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	4.5% 1/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.
Psychiatric disorders Insomnia	3.8% 1/26 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/15 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.	0.00% 0/22 • From start of infusion (Day 1) up to follow-up (Day 35) Safety set included all randomized participants who were administered double-blind study treatment and had analyzed according to the treatment received.