Atrial Fibrillation MedDRA version: 20.0 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Code: AP30663
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AP30663
Current Sponsor code: AP30663
Other descriptive name: APUS0894
Concentration unit: mg/ml m
Sponsors
Acesion Pharma ApS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for study entry, patients must satisfy all of the following criteria: 1. Provision of written informed consent. 2. Clinical indication for cardioversion of atrial fibrillation. 3. Current episode of symptomatic atrial fibrillation lasting between 3 h and 7 days inclusive at randomisation. 4. Adequate anticoagulation according to international and/or national guidelines. 5. Body weight 50 to 110 kg inclusive (with clothes, without shoes). 6. Male patients and postmenopausal women aged 18 to 80 years inclusive. - Male patients who are sexually active must agree to abstain from sexual activity or be willing to use a double-barrier method of birth control (i.e. any double combination of male or female condom with spermicidal gel, diaphragm, sponge or cervical cap with spermicidal gel) if they become sexually active from the time of consent and for 90 days after the infusion day. - Post-menopausal women are defined as being >12 months after last menstrual period. - Women can also be included if permanently sterilised since =6 weeks (i.e. documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy). Breastfeeding women are excluded. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 43 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: 1. Significant clinical illness or surgical procedure within 4 weeks preceding the screening visit. 2. Present renal dysfunction (estimated glomerular filtration rate [eGFR] 3 × upper limit of normal), or uncontrolled hyperthyroidism or hypothyroidism. 3. History of significant mental, renal or hepatic disorder, chronic obstructive pulmonary disease or other significant disease, as judged by the investigator. 4. Any cardioversion attempt of AF or atrial flutter within 1 week preceding randomisation. 5. Prior failed attempt (no conversion) of pharmacological or DC cardioversion of previous or current AF episode. 6. Failure to find a large antecubital (or equivalent) vein for the infusion. 7. Any of the following events, or any other significant cardiovascular event as judged by the investigator, during the last 6 weeks before randomisation: myocardial infarction, unstable angina pectoris or other signs of myocardial ischaemia, stroke or transient ischaemic attack, myocardial revascularisation (percutaneous coronary intervention [PCI], coronary artery bypass graft [CABG]), or other revascularisation procedure. 8. Haemodynamically unstable condition as judged by the investigator; systolic blood pressure (BP) 180 mm Hg, or diastolic BP >105 mm Hg at randomisation. 9. Blood haemoglobin 13 mm). 12. Any clinically significant valvular heart disease. 13. History or previous signs of sinus nodal disease. 14. Pacemaker or implantable cardioverter defibrillator therapy. 15. Personal or family history of Torsades de Pointes, any other polymorphic ventricular tachycardia, sustained ventricular tachycardia, long QT syndrome, and/or Brugada syndrome. 16. QTc (Fridericia, QTcF) interval >450 ms at randomisation. (When measured during AF, the mean heart rate should be 50 to 100 bpm. The QTcF should be calculated at AF as the mean of at least 5 consecutive RR intervals with consecutive QT intervals). 17. QRS duration >120 ms at randomisation. 18. Known atrioventricular (AV)-block I (prolonged PQ [PR] interval >220 ms), AV-block II, AV-block III, or complete bundle branch block (BBB). 19. Potassium in serum below 3.5 or above 5.3 mmol/L at randomisation. Patients with low potassium levels at screening may be appropriately supplemented with potassium before baseline, according to the local standards. A re-test of the potassium level is required, and the patient can be randomised after the potassium has returned to reference range. 20. Anticipated change in dose or initiation of loop diuretic from screening to the end of infusion. 21. Use of any antiarrhythmic drug class I and/or III within 7 days or, for amiodarone specifically, 12 weeks before randomisation. 22. Use of QT-prolonging drug, and/or drug that inhibits cytochrome P450 (CYP)3A4, as well as St John's Wort within 10 days before randomisation. 23. Administration of an investigational drug within the preceding 3 months before randomisation. 24. Administration of AP30663 at any time before randomis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective: To demonstrate the efficacy of 1 or more dose levels of AP30663 on the basis of the ability to convert atrial fibrillation (AF) after intravenous administration;Secondary Objective: To study the stability of rhythm control (immediate relapse of AF [IRAF], i.e. within 5 min after conversion from AF). To study the importance of AF duration with respect to the efficacy and safety of 1 or more dose levels of AP30663. To evaluate the safety and tolerability of 1 or more dose levels of AP30663. To study the relationship between systemic exposure and response, with special regard to the conversion from AF and the effect on QRS and QTcF;Primary end point(s): The proportion of patients that have converted from AF within 90 min from the start of infusion and subsequently have no AF recurrence within 1 min of conversion from AF.;Timepoint(s) of evaluation of this end point: Day 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Endpoints: The time to conversion from AF from start of infusion. The proportion of patients with relapse of AF within 5 min (IRAF) after pharmacological or DC cardioversion. The proportion of patients in SR at 3 h ± 1 h after start of infusion. The proportion of patients in SR at 24 h ± 2 h after start of infusion. The proportion of patients in SR at 30 days ± 5 days after start of infusion Safety Endpoints: Adverse events (AEs), electrocardiogram (ECG) variables including significant arrhythmia, physical examination, vital signs, and laboratory evaluations. Changes in QTcF interval data over time. Pharmacokinetics: Systemic exposure derived from the population PK model. Population PK model parameter estimates derived from plasma concentrations of AP30663.;Timepoint(s) of evaluation of this end point: Efficacy Variables: timepoints are defined within the endpoint. Safety assessments: timepoints as outlined in the Schedule of Assessments in Section 8.1.2 of the protocol. Pharmacokinetic Variables: PK sampling will be taken at baseline (pre-infusion) and at the following time points after start of infusion: 5 min ± 1 min, 15 min ± 1 min, 25 min ± 1 min, 30 min - 1 min (the infusion will not be stopped before the 30-min plasma sample has been collected), 45 min ± 5 min, 1 h ± 5 min, 1 h 30 min ± 5 min, 4 h ± 5 min, 8 h ± 5 min, and 24 h ± 15 min. In the case of conversion from atrial fibrillation within 90 min from the start of infusion, an additional sample will be taken immediately after conversion. | — |
Countries
Denmark, Hungary
Contacts
Public ContactBirgitte Vestbjerg
Acesion Pharma ApS
Outcome results
None listed