Persistent atrial fibrillation MedDRA version: 20.0 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders
Conditions
Sponsors
OMEICOS Therapeutics GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or females between 18 and 85 years of age. 2. Patients with persistent AF for > 7 days but = 3 months who are suitable for electrical DCC. At randomization, the duration of the current episode of persistent AF must be shown to be greater than 7 days and not greater than 3 months, as confirmed by two ECGs (one ECG must be a 12 lead ECG). 3. Male patients must be surgically sterile for at least 90 days or, for males capable of fathering children and who are sexually active with female partners of childbearing potential, will be required to use a male condom with spermicide, and will refrain from donating sperm from the time of the first dose until 90 days after the last dose of study medication. 4. Females of childbearing potential will agree to follow contraception requirements from the time of signing the Informed Consent Form (ICF) until 90 days after the last administration of study drug. o Females are considered of childbearing potential if they are postmenarchal, have not been surgically sterile for at least 6 weeks (i.e., total hysterectomy, bilateral salpingo oophorectomy, or tubal ligation), and are premenopausal (menopause is defined as cessation of menstruation for at least 1 year without an alternative medical cause). Postmenopausal status will be confirmed with a serum follicle stimulating hormone (FSH) test at Screening (FSH > 40 mIU/mL). 5. Willing and able to give written informed consent before any study-related procedure. 6. Willing and able to attend all the visits scheduled in the study. 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 78 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 42
Exclusion criteria
Exclusion criteria: 1. Patients with known concurrent temporary secondary causes of AF such as alcohol intoxication, pulmonary embolism, myocardial infarction, hyperthyroidism, pneumonia, hypoxemia, acute pericarditis or myocarditis, or chronic electrolyte imbalances that may cause cardiac arrhythmias (e.g., potassium 5.5 mmol/L). 2. Patients that have undergone surgical or catheter ablation for AF or atrial flutter. 3. Patients with an existing cardiac treatment device, pacemaker, implantable cardioverter defibrillator, or cardiac resynchronization therapy. 4. Patients with a history of ECG abnormalities that, in the opinion of the investigator (or designee), render the patient unsuitable for the study, including history of congenital or a family history of long QT syndrome, a QTcF = 500 msec and/or a QRS interval = 130 msec at Screening. 5. Patients with congestive heart failure New York Heart Association class III and IV. 6. Patients with left atrium size = 55 mm. 7. Patients with left ventricular ejection fraction = 40 %. 8. Known presence of a thrombus in the left atrial appendage, left atrium, left ventricle, aorta, or intracardial mass. 9. Patients with moderate or severe mitral stenosis, mitral valve rheumatic disease, unresected atrial myxoma, or a mechanical heart valve (patients with bioprosthetic heart valves and/or valve repair can be included) and/or other conditions, such as pulmonary embolism, considered to be formal indication for conventional anticoagulation (patients who have had coronary artery bypass grafts that occurred more than 6 months prior to randomization will not be excluded). 10. Patients with any acute coronary event, stroke, or percutaneous coronary intervention within 6 months prior to randomization or who are receiving dual antiplatelet therapy (regardless of when the event occurred). 11. Uncontrolled/therapy-resistant bradycardia (defined as persistent bradycardia with a heart rate of 180 mmHg or diastolic blood pressure > 110 mmHg) within a 3-month period prior to randomization. 12. Patients having more than two DCCs in the last 6 months. Any unsuccessful pharmacological and/or electrical cardioversion (within prior 3 months). For the purposes of this study, unsuccessful cardioversion is defined as maintaining sinus rhythm for < 2 hours after cardioversion. 13. Patients with signs of bleeding or conditions associated with a high risk of bleeding including major surgeries or biopsies in the 30 days prior to randomization or planned procedures during the study duration. 14. Patients with a positive hepatitis panel and/or positive human immunodeficiency virus test at Screening. Patients whose results are compatible with prior immunization may be included at the discretion of the investigator. 15. Patients taking antiarrhythmic agents (including dronedarone) within 3 days of planned randomization will be excluded. 16. Patients taking oral amiodarone within 3 months of planned randomization. 17. Patients with any contraindication to anticoagulant agents. 18. Patients planning to take any dose of omega-3 fatty acid derivative during the study. 19. Patients with active cancer who are undergoing chemotherapy, radiation, or major surgery within the next 3 months. 20. Patients with any serious intercur
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary efficacy endpoints are: • AF burden (% time with any AF after electrical cardioversion). This is defined as the area under the curve for daily estimates. In case of repeated DCC, the burden for the day of DCC and all following days will be estimated as the median of burden from onset of the current AF episode until DCC. The exploratory efficacy endpoints are: • RecR of non-persistent AF (defined as at least one AF episode not fulfilling the persistent AF definition) • TTR of non persistent AF (defined as at least one AF episode not fulfilling the persistent AF definition) • AF burden during the first week of study drug intake prior to cardioversion • AF burden during the first week of study drug intake prior to cardioversion compared to baseline • AF burden after DCC compared to baseline • Incidence of conversion to sinus rhythm during the first week of study drug intake prior to cardioversion • Incidence of DCC procedures after successful DCC on Visit 4 • Incidence and duration of atrial flutter/atrial tachycardia • Data collected from the patient diaries Safety endpoints are: • Incidence, severity, seriousness, and treatment-causality of AEs • Clinically significant changes in safety laboratory evaluations, vital signs, 12 lead ECGs, ICM data, and physical examinations Pharmacokinetic endpoints are: • Plasma concentrations of OMT-28 at each timepoint • Trough plasma concentration (Ctrough) Additional PK parameters may be calculated as appropriate using a popPK approach. OMT 28 metabolites will be evaluated. Exploratory PD endpoints may include measurement of the following biomarkers: • Growth differentiation factor 15 (GDF15) • Interleukin-6 (IL-6) • High-sensitivity C-reactive protein (hs-CRP) • Transforming growth factor beta 1 (TGF-ß1) • N-terminal pro-A-type natriuretic peptide (NT-proANP) • N terminal pro-B-type natriuretic peptide (NT-proBNP) • Tissue inhibitors of metalloproteinases metallopeptidase | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are: • Recurrence rate (RecR) of persistent AF (defined as AF burden = 23/24 hours over 7 consecutive days) in at least one 7 day period • Time (days) from the successful cardioversion to first documented recurrence (TTR) of persistent AF (defined as AF burden = 23/24 hours over 7 consecutive days) in at least one 7 day period ;Timepoint(s) of evaluation of this end point: An interim analysis will be conducted once approximately 15 patients per study arm have completed the treatment phase (Visit 8) of the study. | — |
Countries
Bulgaria, Czech Republic, Hungary, Ukraine
Contacts
Public ContactSponsor's medical expert
OMEICOS Therapeutics GmbH
Outcome results
None listed