Study of BXCL501 In Agitation Associated With Delirium in ICU Patients

Phase 2

Withdrawn

• Conditions: Delirium; Agitation
• Interventions: Drug: BXCL501; Drug: Placebo film

• Registration Number: NCT05313386
• Lead Sponsor: BioXcel Therapeutics Inc

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2021-02-23
• Study First Submitted: 2021-03-31
• Primary Completion: 2022-02-21
• Study Completion: 2022-02-21
• Status Verified: 2022-04
• Study First Submitted QC: 2022-04-01
• Last Update Submitted: 2022-04-01
• Study First Posted: 2022-04-06
• Last Update Posted: 2022-04-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria for Enrollment (Informed Consent):

1. ICU admitted male and female patients, ≥ 18 years, COVID 19 (+) and (-)

2. Subject or legally appointed representative (LAR) able to read, understand and provide informed consent, or to provide assent

   Inclusion Criteria for Randomization:

3. Positive CAM-ICU

4. RASS score ≥ +1

5. Subject judged to be likely capable of self-administration

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Exclusion Criteria

1. Clinically significant ECG changes, brady- and tachyarrhythmias, QTc prolongation
2. Hepatic dysfunction
3. Pregnancy
4. Known allergy to Dexmedetomidine or Haloperidol.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1- 120 Micrograms	Placebo film	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.
Cohort 2- 180 Micrograms	BXCL501	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.
Cohort 4- 300 Micrograms	BXCL501	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.
Cohort 2- 180 Micrograms	Placebo film	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.
Cohort 1- 120 Micrograms	BXCL501	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.
Cohort 3- 240 Micrograms	BXCL501	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.
Cohort 3- 240 Micrograms	Placebo film	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.
Cohort 4- 300 Micrograms	Placebo film	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.

Primary Outcome Measures

Name	Time	Method
2-point or greater drop in RASS	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

Secondary Outcome Measures

Name	Time	Method
The time to which a 2-point drop is seen in RASS score after starting dose administration	24 Hours	The time to which a 2-point drop is seen in RASS score after starting dose administration.
Overall delirium improvement as measured by the CAM-ICU-7 Total Score during ICU stay	24 Hours	Overall delirium improvement as measured by the CAM-ICU-7 Total Score during ICU stay

Trial Locations

Locations (1)

BioXcel Clinical Research Site; 🇺🇸 Nashville, Tennessee, United States