Dexmedetomidine Sublingual Film for the Management of Agitation in Delirium: Safety and Preliminary Efficacy

• Status: Not yet recruiting
• Trial end date: 2021-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The investigator will examine the safety, tolerability, optimal dose, and preliminary efficacy of dexmedetomidine sublingual film in a randomized, double-blind, controlled trial in 40 hospitalized patients with hyperactive delirium (i.e., delirium with agitation) in the Intensive Care Unit (ICU) setting.

Specific Aim #1 (safety and tolerability): To examine the incidence of cardiovascular and other side effects following the administration of dexmedetomidine sublingual film in patients hospitalized in the ICU with delirium and agitation in a randomized, double-blind trial (total N=80 patients with delirium [with or without agitation], with a goal of administering dexmedetomidine to at least 40 participants with agitation).

Hypothesis: Dexmedetomidine sublingual film will be associated with hypotension and/or bradycardia requiring clinical intervention in ≤ 20% (8 of 40) participants. Dexmedetomidine will not be associated with QTc prolongation or non-cardiac adverse events.

Specific Aim #2 (preliminary efficacy): To examine the impact of dexmedetomidine sublingual film on agitation and delirium severity.

Hypothesis: Dexmedetomidine will lead to reductions in agitation and delirium severity during the follow-up period (co-primary endpoints = 1 and 2 hours post-administration).

Specific Aim #3 (optimal dosing): To identify the minimum dose that is effective at reducing agitation and delirium severity without causing significant side effects.

Hypothesis: Participants receiving doses of 60 mcg of dexmedetomidine will have a faster time to a reduction in agitation and greater reductions in delirium severity than participants receiving 20 mcg of dexmedetomidine.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jeff C. Huffman, MD
• Collaborator: BioXcel Therapeutics Inc
• Treatments: Dexmedetomidine

Criteria

Inclusion Criteria:

• Adults hospitalized on a medical or surgical intensive care unit at MGH

• Diagnosis of delirium, assessed according to DSM-5 criteria (DSM-5)

• Body mass index (BMI) between 18 and 30 kg/m2, inclusive, at screening

• Weight at least 60 kg (132 pounds), at screening

• In the opinion of the study and clinical teams, sufficiently physically healthy to receive dexmedetomidine sublingual film

Exclusion Criteria:

• Per medical record or team report, diagnoses of:

• Dementia

• Significant traumatic brain injury

• History of stroke, with persistent neurologic deficits

• Presence of any of the following cardiovascular comorbidities

• Sick sinus syndrome

• A resting heart rate of < 55 beats per minutes or systolic blood pressure (BP) <100 mmHg or >160 mmHg or diastolic BP <70 mmHg or ˃ 95 mmHg at enrollment and prior to dosing.

• Evidence of cardiac ischemia on a 12-lead electrocardiogram (ECG)

• Corrected QT interval of > 450 msec

• Presence of a permanent pacemaker device

• Per medical record (notes, current medications, flowsheets):

• Second degree (or greater) Atrioventricular (AV) block without a pacemaker

• Known allergy or adverse reaction to dexmedetomidine

• Current use of dexmedetomidine

• Inability to take sublingual dexmedetomidine due to severe agitation, neurological impairment, nil per os (NPO) status, or other cause.

• Hepatic impairment (liver function tests > 3 times the upper limit of normal)

• Severe renal impairment (glomerular filtration rate (GFR) < 30 ml/min or on dialysis)

• Weight < 60 kg

• Pregnancy (in women; tested with serum or urine human chorionic gonadotropin [hCG])

• Non-fluency in English

• Prior enrollment in the study, with receipt of study medication, during the current or a previous hospitalization