A Study Evaluating the Efficacy and Safety of AP30663 for Cardioversion in Participants With Atrial Fibrillation (AF)
- Registration Number
- NCT04571385
- Lead Sponsor
- Acesion Pharma
- Brief Summary
This study will evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of one or more doses of AP30663 for cardioversion in adult participants with AF.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 66
- Clinical indication for cardioversion of AF
- Current episode of symptomatic AF lasting between 3-hour and 7 days (inclusive) at randomization
- Adequate anticoagulation according to international and/or national guidelines
Key
- Significant clinical illness or surgical procedure within 4 weeks preceding the screening visit
- History of significant mental, renal or hepatic disorder, chronic obstructive pulmonary disease, sinus nodal disease, or other significant disease, as judged by the investigator.
- Any cardioversion attempt of AF or atrial flutter within 4 weeks preceding randomization
- Use of any antiarrhythmic drug class I and/or III within 6 months before randomisation
Other protocol defined Inclusion/Exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2: AP30663 AP30663 Participants will receive a single dose of one of the multiple dose levels of AP30663. Part 1: Placebo Placebo Participants will receive placebo matched to AP30663. Part 2: Placebo Placebo Participants will receive placebo matched to AP30663. Part 1: AP30663 AP30663 Participants will receive single dose of AP30663.
- Primary Outcome Measures
Name Time Method 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 Within 90 minutes from the start of infusion (Day 1) 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.
- Secondary Outcome Measures
Name Time Method Time to Conversion From Atrial Fibrillation From Start of Infusion From start of infusion (Day 1) up to Day 2 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.
Percentage of Participants With Relapse of AF Within 5 Minutes (IRAF) After Pharmacological or Direct Current (DC) Cardioversion Within 5 minutes after cardioversion (Day 1) 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.
Maximum Observed Peak Plasma Concentration (Cmax) of AP30663 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 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.
Changes From Baseline in Fridericia's Correction of QT Interval (ΔQTcF) Interval Data Over Time Baseline, 15 minutes, 45 minutes, 2 hours, 8 hours and 24 hours post-dose 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.
Area Under the Concentration Time Curve From Pre-dose Concentration up to 30 Minutes (AUC0-0.5) of AP30663 Baseline (pre-infusion) and at 5, 15, 25, 30 minutes post-infusion 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.
Area Under the Concentration-Time Curve From Pre-dose (Zero) Through Concentration to Infinity (AUC0-inf) of AP30663 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 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs From start of infusion (Day 1) up to follow-up (Day 35) 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.
Percentage of Participants With Sinus Rhythm (SR) at 3 Hours, 24 Hours and Day 30 After Start of Infusion At 3 hours, 24 hours and Day 30 after start of Infusion (Day 1) 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.
Area Under the Concentration Time Curve up to the Last Measurable Concentration (AUC0-t) of AP30663 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 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 to Reach Peak Plasma Concentration (Tmax) of AP30663 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 Tmax was directly determined from concentration time data. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.
Terminal Half Life of (T1/2) of AP30663 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 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.
Elimination Rate Constant (Kel) of AP30663 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 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.
Trial Locations
- Locations (15)
Acesion Pharma Investigational Site 204
🇭🇺Zalaegerszeg, Hungary
Acesion Pharma Investigational Site 110
🇩🇰Aalborg, Denmark
Acesion Pharma Investigational Site 106
🇩🇰Copenhagen, Denmark
Acesion Pharma Investigational Site 108
🇩🇰Hellerup, Denmark
Acesion Pharma Investigational Site 113
🇩🇰Hillerød, Denmark
Acesion Pharma Investigational Site 105
🇩🇰Roskilde, Denmark
Acesion Pharma Investigational Site 207
🇭🇺Budapest, Hungary
Acesion Pharma Investigational Site 214
🇭🇺Budapest, Hungary
Acesion Pharma Investigational Site 212
🇭🇺Budapest, Hungary
Acesion Pharma Investigational Site 211
🇭🇺Pecs, Hungary
Acesion Pharma Investigational Site 210
🇭🇺Szentes, Hungary
Acesion Pharma Investigational Site 202
🇭🇺Budapest, Hungary
Acesion Pharma Investigational Site 201
🇭🇺Szekszárd, Hungary
Acesion Pharma Investigational Site 203
🇭🇺Budapest, Hungary
Acesion Pharma Investigational Site 213
🇭🇺Budapest, Hungary