BXCL501 After Stress to Increase Recovery Success (BASIS)

University of North Carolina (UNC)

Status and phase: Begins enrollment this month; Phase 2

Conditions: Acute Stress Disorder; Post-traumatic Stress Disorder; Acute Stress Reaction

Treatments: Drug: BXCL501 (dexmedetomidine HCl); Drug: Placebo

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT06943404

25-0345

Details and patient eligibility

About

This study will examine the safety and efficacy of BXCL501 to reduce ASR symptoms and behavioral changes among patients presenting to the Emergency Department (ED) after Motor Vehicle Collision (MVC). Specifically, the investigators will perform the BXCL501 (BASIS) Trial, a double-blind placebo-controlled Randomized Controlled Trial (RCT) to determine if BXCL501 (dexmedetomidine hydrochloride sublingual film) initiated in the ED in the hours after MVC to high risk individuals, treats/reduces ASR/ASD symptoms (primary outcome), improves neurocognitive function, and prevents/reduces posttraumatic stress (PTS) symptoms (secondary outcomes) long term. 100 participants will be randomized, receive study drug in ED and be discharged with a 2-week drug supply. Prior to initial dose of study drug administration, and during the hours, days, and weeks after participants will receive serial longitudinal assessments of psychological and somatic symptoms, neurocognitive function, and adverse events.

Full description

U.S. military personnel are exposed to life-threatening traumatic events (e.g., intense firefights with multiple casualties) that result in acute stress reaction (ASR) symptoms (ICD-10) and posttraumatic stress (PTS). Similarly, acute and persistent stress symptoms, and related adverse posttraumatic neuropsychiatric sequelae, are also very common and cause a tremendous burden of suffering in civilian populations following exposure to life-threatening traumatic events (e.g., motor vehicle collision, violent or accidental death of a loved one, and assault). BXCL501 (dexmedetomidine HCl sublingual film) has been evaluated in multiple clinical trials across a range of medical conditions (dementia, schizophrenia, bipolar disorder, opioid use disorder), with an excellent safety profile, and evidence of efficacy with respect to decreasing agitation. This is promising for the treatment of ASRs, as agitation is a primary feature of ASRs in many individuals. Additionally, adrenergic hyperactivity is also a key characteristic of ASRs and contributes to the development of Posttraumatic Stress Disorder (PTSD). BXCL501 is known to decrease the activity of central noradrenergic neurons, suggesting a mechanistic pathway by which BXCL501 may improve outcomes for individuals at risk of ASR/ASD/PTSD. BXCL501 therefore holds significant promise as a treatment aimed at reducing ASR symptoms and related behavioral changes, enhancing resilience and improving warfighter performance, and reducing the frequency and severity of persistent/chronic PTS symptoms. This study will evaluate the safety and efficacy of BXCL501 in a population of trauma survivors at high risk for developing ASR, ASD, and PTSD symptoms, and may ultimately provide military personnel, veterans, and civilians with an important new treatment option to improve recovery, job performance, and quality of life when administered in the early aftermath of exposure to a traumatic stressor.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ≥ 18 years and ≤ 65 years of age
• Admitted to ED within 24 hours of MVC
• Anticipated to be discharged home from the ED
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Consent to receive unencrypted communications
• Has a smartphone with continuous service for ≥ 1 year
• Has a personal email address they regularly access
• Able to speak and read English
• PTS prediction tool risk score ≥ 16 in the ED
• Females of childbearing potential (not surgically sterilized (tubal ligation/hysterectomy) or not post-menopausal (no menstrual period for > 6 months)) must be willing to use a medically acceptable and effective birth control method for 3 months before the study and while participating in the study. Medically acceptable methods of contraception that may be used by the participant include abstinence, birth control pills or patches, birth control implants, diaphragm, intrauterine device (IUD), or condoms.

Exclusion criteria

• Substantial comorbid injury (e.g., long bone fracture)
• People of childbearing potential who are pregnant, breastfeeding, planning to become pregnant, or not using a highly effective form of contraception (e.g., implants, intrauterine devices (IUDs), tubal ligation, hormonal birth control pills, patches, vaginal rings, or injections) during their participation
• Prisoner status
• Chronic daily opioid use prior to MVC (> 20 mg oral daily morphine equivalents)
• Bipolar disorder, psychotic disorder, active psychosis, suicidal ideation, or homicidal ideation
• Plans for hospital admission
• Clinically significant history of cardiac disease including (a) history of syncope or other syncopal attacks; (b) current evidence of orthostatic hypotension (defined as a decrease in systolic BP of 20 mm Hg or decrease in diastolic BP of 10 mm Hg within 3 minutes); (c) resting heart rate of <55 beats per minute; (d) systolic blood pressure <110 mm Hg or diastolic BP <70 mm Hg; (e) participants with a corrected QT interval (QTc) interval >440msec (males) or >460msec (females) not in sinus rhythm; or 1st, 2nd or 3rd degree hearth block; or (f) history of severely impaired ventricular function (ejection fraction < 30%).
• Hypomagnesia (<1.7 mg/dL) or hypokalemia (< 3.0 Milliequivalents (mEq/L))
• Substantial hepatic impairment (e.g. Aspartate Transaminase (AST) or Alanine Transaminase (ALT) > 3 times the upper limit of normal or history of cirrhosis).
• Currently taking the following medications: a) medications for alcoholism (e.g. naltrexone, disulfiram, topiramate, acamprosate); b) psychotropic medications that promote sedation including sedative/hypnotics, barbiturates, antihistamines, sedative antidepressants (e.g. doxepin, mirtazapine, trazodone), and triptans (e.g., sumatriptan); c) alpha-2-adrenergic agonists (clonidine, guanfacine, lofexidine); d) or adrenergic agents prescribed for other reasons (prazosin). (Permitted Concomitant Medications: The concomitant medications allowed in the study include non-sedative antidepressants used to treat PTSD)
• Hypersensitivity or history of allergic reaction to dexmedetomidine
• Lacking capacity to provide informed consent (receipt of sedative, hypnotic agent making the patient non-decisional for consent)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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100 participants in 2 patient groups, including a placebo group

BXCL501 (dexmedetomidine HCl)

Experimental group

Description:

Participants will be instructed to take an initial dose of BXCL501 (equivalent to 1 film, 120mcg) in the ED as part of enrollment procedures. If the time between the first dose and the planned bedtime of the participant is greater than 6 hours, participants will be instructed to take the second dose at bedtime on the day of enrollment. If the time between the first dose and the planned bedtime of the participant is less than 6 hours participants will be instructed to take the second dose before bedtime on the day following enrollment. Following the initial dosing on the day of enrollment, all participants will be instructed to take a dose of study medication before bedtime until they have completed 14 days of treatment.

Treatment:

Drug: BXCL501 (dexmedetomidine HCl)

Placebo

Placebo Comparator group

Description:

Participants will be instructed to take an initial dose of placebo (equivalent to 1 film, 120mcg) in the ED as part of enrollment procedures. If the time between the first dose and the planned bedtime of the participant is greater than 6 hours, participants will be instructed to take the second dose at bedtime on the day of enrollment. If the time between the first dose and the planned bedtime of the participant is less than 6 hours participants will be instructed to take the second dose before bedtime on the day following enrollment. Following the initial dosing on the day of enrollment, all participants will be instructed to take a dose of study medication before bedtime until they have completed 14 days of treatment.

Treatment:

Drug: Placebo