Prevention/Reduction of ASRs and PTSD to Sustain Civilian Performance With Sublingual Cyclobenzaprine HCl (TNX-102 SL)

NCT06636786 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-0711
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 9

Brief Summary

This study will examine the safety and efficacy of TNX-102 SL 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 Optimizing Acute Stress reaction Interventions with TNX-102 SL (OASIS) Trial, a double-blind placebo-controlled randomized clinical trial (RCT) to determine if TNX-102 SL initiated in the ED in the hours after MVC to high risk individuals, treats/reduces acute stress reaction (ASR)/acute stress disorder (ASD) symptoms (primary outcome), improves neurocognitive function, and prevents/reduces posttraumatic stress (PTS) symptoms (secondary outcomes) long term. 180 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.

Conditions

Acute Stress Reaction; Acute Stress Disorder; Neurocognitive Function; Post-traumatic Stress

Outcome Measures

Primary Outcomes (1)

• Change in ASD Score

  Individuals are asked to complete the 14-item Acute Stress Disorder Scale (ASDS) self-report inventory where each item is rated on a 5-point scale (0= Not at all; 1= Mildly; 2= Medium; 3= Quite a bit; 4= Very Much) that indexes acute stress disorder (ASD). Range of possible total scores is 0-56, with higher total scores indicating greater acute stress symptoms.

  Week 1, 3 after MVC

Secondary Outcomes (8)

• Median reaction time of correct responses (general cognitive function)

  Min 30, Hour 1, 6, 12, Day 1, 2, 3, Week 1, 2, 3, 5, 6, 8, 11, 12 after MVC

• Median reaction time of correct responses (procedural reaction time)

  Min 30, Hour 1, 6, 12, Day 1, 2, 3, Week 1, 2, 3, 5, 6, 8, 11, 12 after MVC

• Proportion of targets correctly identified (visuospatial processing and attention)

  Min 30, Hour 1, 6, 12, Day 1, 2, 3, Week 1, 2, 3, 5, 6, 8, 11, 12 after MVC

• d-prime identification (psychomotor vigilance)

  Min 30, Hour 1, 6, 12, Day 1, 2, 3, Week 1, 2, 3, 5, 6, 8, 11, 12 after MVC

• Change in Pain Symptom Score

  Baseline, Week 1, 3, 6, 12 after MVC

Study Arms (2)

Cyclobenzaprine HCl

EXPERIMENTAL

Participants will be instructed to take a half dose (equivalent to 1 tablet, 2.8 mg) of Cyclobenzaprine HCl in the ED as part of enrollment procedures. If the time between the first half dose and the planned bedtime of the participant is less than 6 hours, participants will be instructed to take 1 tablet (half dose) the first night at bedtime. If the time between the first half dose and planned bedtime of the participant is greater than or equal to 6 hours, then participants will be instructed to take a full dose (equivalent to 2 tablets) the first night. Over the following 13 days, all participants will be instructed to take a full dose of the study drug at bedtime. Each participant will receive 29 tablets and take either 28 or 29 tablets total for the duration of study participation.

Drug: Cyclobenzaprine HCl

Placebo

PLACEBO COMPARATOR

Participants will be instructed to take a half dose (equivalent to 1 tablet, 2.8 mg) of placebo in the ED as part of enrollment procedures. The placebo is the same formulation as active except the Cyclobenzaprine HCl content is replaced by Mannitol to maintain the same tablet weight and dimensions. If the time between the first half dose and the planned bedtime of the participant is less than 6 hours, participants will be instructed to take 1 tablet (half dose) the first night at bedtime. If the time between the first half dose and planned bedtime of the participant is greater than or equal to 6 hours, then participants will be instructed to take a full dose (equivalent to 2 tablets) the first night. Over the following 13 days, all participants will be instructed to take a full dose of the study drug at bedtime. Each participant will receive 29 tablets and take either 28 or 29 tablets total for the duration of study participation.

Drug: Placebo

Interventions

Cyclobenzaprine HCl DRUG

TNX-102 SL (cyclobenzaprine HCl sublingual tablets) taken sublingually (under the tongue) in the ED and each day at bedtime for a total of 2 weeks.

Also known as: TNX-102 SL

Cyclobenzaprine HCl

Placebo DRUG

Placebo sublingual tablets taken sublingually (under the tongue) in the ED and each day at bedtime for a total of 2 weeks.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• ≥ 18 years and ≤ 55 years of age
• Presentation to ED within 72 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
• Pain severity in the ED ≥ 4 (0-10 numeric rating scale)
• People who are not of childbearing potential (e.g., hysterectomy, bilateral oophorectomy, or confirmed postmenopausal for at least last 12 consecutive months)
• People with the capacity to conceive a pregnancy must agree to employ a highly effective form of birth control throughout the first 21 days of study participation (e.g., oral, injected, transdermal, or implanted hormonal methods of contraception for at least one full menstrual cycle prior to study drug administration; placement of an intrauterine device (IUD) or intrauterine system (IUS); or double barrier methods such as condoms and diaphragms)

You may not qualify if:

• 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
• Any chronic daily opioid use prior to MVC
• Active psychosis, suicidal ideation, or homicidal ideation
• Plans for hospital admission
• History of arrhythmias, heart block or conduction disturbances, congestive heart failure
• Currently in the acute recovery phase of myocardial infarction
• Hypersensitivity to cyclobenzaprine or the excipient in TNX-102 SL or placebo formulations
• History of urinary retention, angle-closure glaucoma, increased intraocular pressure, or hyperthyroidism (TSH \< lower limit of normal)
• Concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after their discontinuation due to risk of potential fatal drug-drug interactions
• Any hepatic impairment or renal disease (defined as AST OR ALT \> 3 times the upper limit of normal) or renal disease (defined as GFR ≤ 80 mL/min)
• Lacking capacity to provide informed consent (receipt of sedative, hypnotic agent making the patient non-decisional for consent)
• Any other history or condition that would, in the site investigator's judgement, indicate that the patient would very likely be non-compliant with the study or unsuitable for the study (e.g., might interfere with the study, confound interpretation, or endanger patient)
• Elevated baseline blood pressure defined as systolic blood pressure ≥ 170 mmHg or diastolic blood pressure ≥ 100 mmHg and or elevated heart rate of ≥115

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• United States Department of Defense: collaborator
• Tonix Pharmaceuticals, Inc.: collaborator
• Cooper University Health Care: collaborator
• Mclean Hospital: collaborator

Study Sites (9)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

NOT YET RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Washington University in St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

Cooper University Health System

Camden, New Jersey, 08103, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

The Miriam Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Stress Disorders, Traumatic, Acute

Interventions

cyclobenzaprine; Sugars

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

• Samuel McLean, MD

  University of North Carollina at Chapel Hill

  PRINCIPAL INVESTIGATOR

• Christopher Jones, MD

  Cooper University Health Care

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Romina Soudavari

CONTACT

9843195030; romina_soudavari@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2024
• First Posted: October 15, 2024
• Study Start: March 25, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Beginning 12 months following publication and continuing for 36 months.
• Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.

Locations

US (9)