A Double-Blind, Randomised, Placebo-Controlled, Parallel-Group Study of AP30663 Given Intravenously for Cardioversion in Patients with Atrial Fibrillatio

Phase 1

• Conditions: Atrial Fibrillation; MedDRA version: 20.0 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2018-004445-17-HU
• Lead Sponsor: Acesion Pharma ApS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-03
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 108

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 (AF).
3. Current episode of symptomatic AF 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

1. Significant clinical illness or surgical procedure within 4 weeks preceding the screening visit.
2. Present renal dysfunction (estimated glomerular filtration rate [eGFR]< 30 mL/min), hepatic dysfunction (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 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 (AFl) within 4 weeks 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 (TIA), 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 BP <90 mmHg or >180 mmHg, or diastolic BP >105 mmHg at randomisation.
9. Blood haemoglobin <100 g/L at screening.
10. Congestive heart failure New York Heart Association class III or IV. Left ventricular ejection fraction <40% on echocardiography, or other clinically significant abnormality on the echocardiogram (not older than 6 months) as judged by the investigator.
11. Known hypertrophic cardiomyopathy or significant left ventricular hypertrophy (free wall or septal thickness >13 mm).
12. Any clinically significant valvular heart disease.
13. History or previous signs of sinus nodal disease, including sinus bradycardia <50 beats per minute (bpm).
14. Pacemaker or implantable cardioverter defibrillator (ICD) 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), or a ventricular rate <60 bpm during AF.
19. Potassium in serum or plasma below 3.5 or above 5.3 mmol/L at randomisation.
20. Need for the use of loop diuretic from screening to the end of infusion.
21. Previous or current use of any anti-arrhythmic drug class I and/or III for maintenance of SR.
22. Use of digitalis glycoside, QT-prolonging drug, and/or drug that inhibits cytochrome P450 (CYP)3A4, as well as St John's Wort within 10 days before randomis

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified