Study on OMT-28 in Maintenance of Sinus Rhythm in Patients With Persistent Atrial Fibrillation (AF)

Study Overview
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Brief Summary
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This is a randomized, double-blind, dose-finding, placebo-controlled, parallel group, multicenter, phase II study to evaluate the efficacy, safety, and popPK of three different doses of OMT-28 given once daily versus placebo in patients with persistent AF.

Detailed Description
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This is a randomized, double-blind, dose-finding, placebo-controlled, parallel group, multicenter, phase II study to evaluate the efficacy, safety, and popPK of three different doses of OMT-28 given once daily versus placebo in patients with persistent AF. 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) and further patient enquiry (including doctor visits, hospital admissions, symptom onset, etc.). A sample size re-evaluation will be performed to avoid an underpowered study because of imprecise estimates for the study population or overoptimistic parameter estimates. Therefore, an interim analysis will re-evaluate sample size assumptions after approximately 15 patients per study arm ( 50 % of planned sample) have completed the treatment phase (Visit 8) of the study. Predefined rules will govern the decision for adjustment of sample size. Patients will be monitored for cardiac events throughout the study using an Implantable Cardiac Monitor (ICM). Safety will be monitored throughout the study. Blood samples will be collected in pre-specified windows for popPK analysis and at pre-specified timepoints for PK/PD analysis. Patients will be provided with a diary to record timing of drug administration and clinical symptoms while not on site. Diaries will be reviewed and checked for compliance at each non-resident visit to the clinical site.

Official Title
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A Placebo-controlled, Double-blind, Randomized, Dose-finding Phase II Study on OMT-28 in MaIntenance of Sinus Rhythm After Electrical Cardioversion in Patients With Persistent Atrial Fibrillation (PROMISE-AF)

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: OMT-28
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females between 18 and 85 years of age. Patients with persistent AF for > 7 days but ≤ 3 months suitable for electrical DCC. Male patients must be surgically sterile for at least 90 days or 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. Females of childbearing potential (postmenarchal, not surgically sterile, premenopausal) 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. Willing and able to give written informed consent before any study-related procedure. Willing and able to attend all the visits scheduled in the study. Main Exclusion Criteria: Patients with known concurrent temporary secondary causes of AF Patients that have undergone surgical or catheter ablation for AF or atrial flutter. Patients with an existing cardiac treatment device, pacemaker, implantable cardioverter defibrillator, or cardiac resynchronization therapy. Patients with a history of ECG abnormalities that, in the opinion of the investigator (or designee), render the patient unsuitable for the study. Patients with congestive heart failure (NYHA class III and IV). Patients with left atrium size ≥ 55 mm. Patients with left ventricular ejection fraction ≤ 40 %. Known presence of a thrombus in the left atrial appendage, left atrium, left ventricle, aorta, or intracardial mass. Patients with moderate or severe mitral stenosis, mitral valve rheumatic disease, unresected atrial myxoma, or a mechanical heart valve and/or other conditions, such as pulmonary embolism, considered to be formal indication for conventional anticoagulation. Patients with any acute coronary event, stroke, or percutaneous coronary intervention within 6 months prior to randomization or who are receiving dual antiplatelet therapy. Uncontrolled/therapy-resistant bradycardia and/or uncontrolled/therapy-resistant hypertension within a 3-month period prior to randomization. Patients having more than two DCCs in the last 6 months. Any unsuccessful pharmacological and/or electrical cardioversion (within prior 3 months). Patients with signs of bleeding or conditions associated with a high risk of bleeding. Patients taking antiarrhythmic agents within 3 days of planned randomization will be excluded. Patients concurrently participating in another study or unable to communicate. Patients with active cancer, chronic kidney disease or intercurrent illness. Pregnant or breastfeeding women. Patients taking concomitant medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low OMT-28<br>Verum, low OMT-28 | Drug: OMT-28<br>* 1 capsule given daily orally from Visit 3 (Day 1) to Visit 8 (Day 99 ± 3 days).<br>|
| Experimental: Middle OMT-28<br>Verum, middle OMT-28 | Drug: OMT-28<br>* 1 capsule given daily orally from Visit 3 (Day 1) to Visit 8 (Day 99 ± 3 days).<br>|
| Experimental: High OMT-28<br>Verum, high OMT-28 | Drug: OMT-28<br>* 1 capsule given daily orally from Visit 3 (Day 1) to Visit 8 (Day 99 ± 3 days).<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* 1 capsule given daily orally from Visit 3 (Day 1) to Visit 8 (Day 99 ± 3 days).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of AF Burden After OMT-28 Administration | To assess the AF burden, based on data collected via the implantable cardiac monitor BioMonitor 2-AF, of three different doses of OMT-28 administered once daily versus placebo in the maintenance of normal sinus rhythm after electrical direct current cardioversion (DCC) in patients with persistent AF | Up to 4.5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | To assess the incidence of treatment-emergent Adverse Events of three different doses of OMT-28 administered once daily versus placebo after electrical DCC in patients with persistent AF. | Up to 4.5 months | 
| Assessment of Pharmacokinetic (PK) Parameters of OMT-28 - AUC | To assess the pharmacokinetic (PK) parameter AUC of OMT-28 administered once daily in patients with persistent AF, by means of population PK (popPK) analysis. | Up to 3.5 months | 
| Assessment of Pharmacokinetic (PK) Parameters of OMT-28 - Cmax | To assess the pharmacokinetic (PK) parameter Cmax of OMT-28 administered once daily in patients with persistent AF, by means of population PK (popPK) analysis. | Up to 3.5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Electrical Cardioversion, Dose-finding