A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-controlled, Ascending Starting Dose Finding, Safety, and Efficacy Study of BXCL501 in Agitation Associated With Delirium in ICU Patients.
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- 2-point or greater drop in RASS
研究概览
简要总结
This study is designed to determine and evaluate the optimal BXCL501 starting dose (StartD) that will safely and effectively reduce agitation associated with delirium in ICU patients. This is an ascending adaptive dose study evaluating the safety and efficacy of four potential starting doses of BXCL501 (120 μg, 180 μg, 240 μg, and 300 μg) in reducing agitation levels in adult ICU patients with delirium. For subjects 65 years of age and older, the potential doses will be reduced 50% in line with the Precedex (reference drug) label. The purpose of this clinical trial is to identify an optimally safe and effective BXCL501
详细描述
This is a Phase 2, randomized, double-blind, placebo-controlled, ascending starting dose finding study assessing safety, efficacy, tolerability and PK of BXCL501 in four starting dose cohort groups to reduce agitation levels associated with delirium in patients within the ICU setting. Evaluation of four BXCL501 starting doses compared to placebo will be conducted according to the following ascending doses: Cohort 1 (120 μg or placebo); Cohort 2 (180 μg or placebo); Cohort 3 (240 μg or placebo); Cohort 4 (300 μg or placebo). For subjects 65 years of age and older, the starting doses in each cohort will be reduced 50% in line with the Precedex (reference drug) label. Safety, efficacy, and tolerability will be assessed throughout the treatment period at various timepoints. Subjects will receive the first starting dose (BXCL501 or placebo) when Baseline RASS score is ≥ +1. Repeat doses may be administered in increments of 120 μg every 3 to 6 hours post first dose (StartD) only if the RASS score remains ≥ +1. For subjects 65 years and older, repeat doses may start in increments of 60 μg every 3 to 6 hours post first dose only if RASS is still ≥+1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Randomized, double-blind, placebo-controlled
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria for Enrollment (Informed Consent):
- •ICU admitted male and female patients, ≥ 18 years, COVID 19 (+) and (-)
- •Subject or legally appointed representative (LAR) able to read, understand and provide informed consent, or to provide assent
- •Inclusion Criteria for Randomization:
- •Positive CAM-ICU
- •RASS score ≥ +1
- •Subject judged to be likely capable of self-administration
排除标准
- •Clinically significant ECG changes, brady- and tachyarrhythmias, QTc prolongation
- •Hepatic dysfunction
- •Known allergy to Dexmedetomidine or Haloperidol.
研究组 & 干预措施
Cohort 1- 120 Micrograms
120 Micrograms film or Placebo film are given to patients in 3:1 ratio respectively.
Repeat doses may be administered in increments of 120 μg every 3 to 6 hours post first dose (StartD) only if the RASS score remains ≥ +1. For subjects 65 years and older, repeat doses may start in increments of 60 μg every 3 to 6 hours post first dose only if RASS is still ≥+1.
干预措施: BXCL501 (Drug)
Cohort 4- 300 Micrograms
One 120 Micrograms film and one 180 Micrograms film or two Placebo films are given to patients in 3:1 ratio respectively.
Repeat doses may be administered in increments of 120 μg every 3 to 6 hours post first dose (StartD) only if the RASS score remains ≥ +1. For subjects 65 years and older, repeat doses may start in increments of 60 μg every 3 to 6 hours post first dose only if RASS is still ≥+1.
干预措施: BXCL501 (Drug)
Cohort 1- 120 Micrograms
120 Micrograms film or Placebo film are given to patients in 3:1 ratio respectively.
Repeat doses may be administered in increments of 120 μg every 3 to 6 hours post first dose (StartD) only if the RASS score remains ≥ +1. For subjects 65 years and older, repeat doses may start in increments of 60 μg every 3 to 6 hours post first dose only if RASS is still ≥+1.
干预措施: Placebo film (Drug)
Cohort 2- 180 Micrograms
180 Micrograms film or Placebo film are given to patients in 3:1 ratio respectively.
Repeat doses may be administered in increments of 120 μg every 3 to 6 hours post first dose (StartD) only if the RASS score remains ≥ +1. For subjects 65 years and older, repeat doses may start in increments of 60 μg every 3 to 6 hours post first dose only if RASS is still ≥+1.
干预措施: BXCL501 (Drug)
Cohort 2- 180 Micrograms
180 Micrograms film or Placebo film are given to patients in 3:1 ratio respectively.
Repeat doses may be administered in increments of 120 μg every 3 to 6 hours post first dose (StartD) only if the RASS score remains ≥ +1. For subjects 65 years and older, repeat doses may start in increments of 60 μg every 3 to 6 hours post first dose only if RASS is still ≥+1.
干预措施: Placebo film (Drug)
Cohort 3- 240 Micrograms
Two 120 Micrograms films or two Placebo films are given to patients in 3:1 ratio respectively.
Repeat doses may be administered in increments of 120 μg every 3 to 6 hours post first dose (StartD) only if the RASS score remains ≥ +1. For subjects 65 years and older, repeat doses may start in increments of 60 μg every 3 to 6 hours post first dose only if RASS is still ≥+1.
干预措施: Placebo film (Drug)
Cohort 4- 300 Micrograms
One 120 Micrograms film and one 180 Micrograms film or two Placebo films are given to patients in 3:1 ratio respectively.
Repeat doses may be administered in increments of 120 μg every 3 to 6 hours post first dose (StartD) only if the RASS score remains ≥ +1. For subjects 65 years and older, repeat doses may start in increments of 60 μg every 3 to 6 hours post first dose only if RASS is still ≥+1.
干预措施: Placebo film (Drug)
Cohort 3- 240 Micrograms
Two 120 Micrograms films or two Placebo films are given to patients in 3:1 ratio respectively.
Repeat doses may be administered in increments of 120 μg every 3 to 6 hours post first dose (StartD) only if the RASS score remains ≥ +1. For subjects 65 years and older, repeat doses may start in increments of 60 μg every 3 to 6 hours post first dose only if RASS is still ≥+1.
干预措施: BXCL501 (Drug)
结局指标
主要结局
2-point or greater drop in RASS
时间窗: 120 minutes
Identification of the dose leading to a 2-point or greater drop in RASS at 2 hours after starting dose administration, with initial RASS not ≤ -3
次要结局
- The time to which a 2-point drop is seen in RASS score after starting dose administration(24 Hours)
- Overall delirium improvement as measured by the CAM-ICU-7 Total Score during ICU stay(24 Hours)