Study of BXCL501 In Agitation Associated With Delirium in ICU Patients

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.

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

Study Overview

• Status: Withdrawn
• Conditions: Delirium; Agitation
• Intervention / Treatment: Drug: BXCL501; Drug: Placebo film

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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • BioXcel Clinical Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: BXCL501; BXCL501 is given in a film form; Other Names: Dexmedetomidine; Drug: Placebo film; Placebo is given in a film form
Experimental: 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.	Drug: BXCL501; BXCL501 is given in a film form; Other Names: Dexmedetomidine; Drug: Placebo film; Placebo is given in a film form
Experimental: 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.	Drug: BXCL501; BXCL501 is given in a film form; Other Names: Dexmedetomidine; Drug: Placebo film; Placebo is given in a film form
Experimental: 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.	Drug: BXCL501; BXCL501 is given in a film form; Other Names: Dexmedetomidine; Drug: Placebo film; Placebo is given in a film form

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-point or greater drop in RASS	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	120 minutes

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: BioXcel Therapeutics Inc
• Collaborators: Cognitive Research Corporation

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2021
• Primary Completion (Anticipated): February 21, 2022
• Study Completion (Anticipated): February 21, 2022

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: April 1, 2022
• First Posted (Actual): April 6, 2022

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 1, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Dyskinesias; Psychomotor Disorders; Delirium; Psychomotor Agitation; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: BXCL501-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No