A Prospective Phase I/II Dose Escalation Pilot Analysis of Ruboxistaurin (LY333531) for Safety in New York Heart Failure Classification III-IV Patients, As Well As For Efficacy in Acutely Augmenting Cardiac Function.
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Percent of patients with a new onset, clinically significant arrhythmia or conduction system disease,
研究概览
简要总结
This study evaluates the effect of ruboxistaurin for its safety, tolerability, and effectiveness in treating adult patients with heart failure. Patients will receive 1 dose of oral ruboxistaurin.
详细描述
Ruboxistaurin is a drug initially developed for treatment of diabetic peripheral retinopathy. The proposed indication for ruboxistaurin in this study is the treatment of adult patients with New York Heart Failure Association (NYHA) Class III-IV heart failure. Ruboxistaurin is a protein kinase c-alpha (PKC-alpha) inhibitor and thus will produce an inotropic effect in the heart which holds the potential to improve cardiac function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 30-75 years of age, inclusive
- •NYHA Class III-IV heart failure (HF) confirmed left ventricular systolic dysfunction with left ventricular ejection fraction (LVEF) <40% as assessed by noninvasive imaging studies such as echocardiography or cardiac MRI within the last 6 months admitted with decompensated heart failure and almost ready for clinical discharge
- •Patient must have had adequate therapy for acute decompensated HF (heart failure) episode prior to enrollment
排除标准
- •Patients with acute coronary syndrome
- •Resynchronization therapy initiated less than 90 days prior to enrollment
- •(LVAD) left ventricular assist device or heart transplantation expected within the next 3 months
- •Patients on hemodialysis or end stage renal disease (ESRD)
- •Patients with serum albumin less than 3 g/dL or evidence of liver cirrhosis
- •Patients with uncontrolled arterial hypertension (systolic blood pressure > 180 or diastolic blood pressure >110)
- •Patients with severe valvular heart disease
- •Patients with acute myocarditis
- •Patients with serum creatinine >3.0 mg/dl or BUN >70 mg/dL
- •Patients with hemodynamic instability or significant active arrhythmias
- •Patients currently on intravenous inotropic therapy or those that have received inotropic therapy within the last 24 hours prior to study enrollment
- •Patients currently on CYP3A inhibitors, or patients that have taken CYP3A inhibitors within 3 months prior to enrollment
- •Patients with ongoing ischemia
- •Patients who have had a myocardial infarction within 30 days prior to study enrollment
- •Patients who are pregnant, nursing, or planning to become pregnant during the study period
研究组 & 干预措施
Ruboxistaurin 64 mg
ruboxistaurin, 64 mg as 1 capsule by mouth with water, 1 time administration
干预措施: Ruboxistaurin (Drug)
Ruboxistaurin 128 mg
ruboxistaurin, 128 mg as 2 capsules by mouth with water, 1 time administration
干预措施: Ruboxistaurin (Drug)
Ruboxistaurin 256 mg
ruboxistaurin, 256 mg as 4 capsules by mouth with water, 1 time administration
干预措施: Ruboxistaurin (Drug)
结局指标
主要结局
Percent of patients with a new onset, clinically significant arrhythmia or conduction system disease,
时间窗: 48 hours
EKG and continuous holter monitoring will be performed. Determination of clinically significant arrhythmia will be determined by a blinded electrophysiologist; intent to treat population
Percent of patients with significant prolongation in the corrected QT (QTc) interval
时间窗: 24 hours
Interpreted by a blinded electrophysiologist. A significant QTc prolongation will be defined as an increase from normal baseline (\<440 msec) to greater than 440 msec OR an increase of equal to or more than 5% from baseline for those subjects with a baseline QTc of \>440 msec.; Intent to treat population
Percent of patients with significant increase in liver function tests
时间窗: 12 hours
An abnormal change in liver function tests will be defined as an increase to 2x the upper limits of normal for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) OR a 50% increase from baseline values. Intent to treat population
Percent of patients with a significant increase in serum creatinine not explained by diuretic use.
时间窗: 12 hours
An abnormal change in serum creatinine will be defined as a 50% increase from baseline values. Of note, changes in Blood Urea Nitrogen (BUN) and creatinine may be secondary to diuretic use and intravascular volume depletion. Intent to treat population
Percent of patient with a significant increase in serum creatine phosphokinase (CPK) levels
时间窗: 12 hours
An abnormal change in serum CPK will be defined as an increase to 2x the upper limits or normal OR a 50% increase from baseline values. Intent to treat population
次要结局
- Change in self-reported well-being, fatigue and dyspnea(8 hours, 24 hours)
- Percent of patients experiencing at least one adverse event(30 days)
- Change in cardiac contractility as assessed by echocardiography.(4 hours)