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

Exclusion Criteria

• •1. Substantial comorbid injury (e.g., long bone fracture)
• •2. 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
• •3. Prisoner status
• •4. Any chronic daily opioid use prior to MVC
• •5. Active psychosis, suicidal ideation, or homicidal ideation
• •6. Plans for hospital admission
• •7. History of arrhythmias, heart block or conduction disturbances, congestive heart failure
• •8. Currently in the acute recovery phase of myocardial infarction
• •9. Hypersensitivity to cyclobenzaprine or the excipient in TNX-102 SL or placebo formulations
• •10. History of urinary retention, angle-closure glaucoma, increased intraocular pressure, or hyperthyroidism (TSH \< lower limit of normal)
• •11. Concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after their discontinuation due to risk of potential fatal drug-drug interactions
• •12. Current or planned use of the following prohibited concomitant medications during study participation: anticholinergic medications, guanethidine, selective serotonin reuptake inhibitors (SSRIs) , serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, MAO inhibitors, anticholinergic medications, guanethidine, potent cytochrome P450 subtype 3A4 inhibitor, St. John's wort, chronic use muscle relaxants or planned use after MCV or other prohibited concomitant medications listed in section 5.6. PI to assess individual cases where single dose of muscle relaxant is prescribed in ED for inclusion
• •13. 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)
• •14. Lacking capacity to provide informed consent (receipt of sedative, hypnotic agent making the patient non-decisional for consent)
• •15. 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)
• •16. Elevated baseline blood pressure defined as systolic blood pressure ≥ 170 mmHg or diastolic blood pressure ≥ 100 mmHg and or elevated heart rate of ≥115
• •17. Abnormal baseline ECG as defined as: QRS duration ≥ 120 ms; QTc \> 460 ms; not in sinus rhythm; or 1st, 2nd, or 3rd degree heart block indicated
• •18. Substance or alcohol use disorder, bipolar disorder, or schizophrenia
• •19. History of severe or unexplained oral, or oropharyngeal swelling or edema