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)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 136
- 试验地点
- 25
- 主要终点
- Assessment of AF Burden After OMT-28 Administration
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo
Placebo
干预措施: Placebo (Drug)
Low OMT-28
Verum, low OMT-28
干预措施: OMT-28 (Drug)
Middle OMT-28
Verum, middle OMT-28
干预措施: OMT-28 (Drug)
High OMT-28
Verum, high OMT-28
干预措施: OMT-28 (Drug)
结局指标
主要结局
Assessment of AF Burden After OMT-28 Administration
时间窗: Up to 4.5 months
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
次要结局
- Incidence of Treatment-Emergent Adverse Events(Up to 4.5 months)
- Assessment of Pharmacokinetic (PK) Parameters of OMT-28 - AUC(Up to 3.5 months)
- Assessment of Pharmacokinetic (PK) Parameters of OMT-28 - Cmax(Up to 3.5 months)