Safety and Efficacy Study of TNX-102 SL in Participants With PTSD

Study Overview
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Brief Summary
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This is a 12-week, multicenter, randomized, double-blind, placebo-controlled, fixed-dose study that will investigate the efficacy and safety of 5.6 mg TNX-102 SL (2 x 2.8 mg tablets)-a sublingual formulation of cyclobenzaprine. Following successful screening and randomization, eligible patients will have a telephonic visit at week 2 and then return regularly to the study clinic for monthly visits for assessments of efficacy and safety.

Official Title
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A Phase 2, Double-Blind, Randomized, Multicenter, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Daily Bedtime TNX-102 SL in Participants With PTSD

Conditions
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PTSD

Intervention / Treatment
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* Drug: TNX-102 SL
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between 18 and 75 years of age, at the time of signing ICF, inclusive. Diagnosed with current (past month) PTSD as determined by the MINI 7.0.2 Module H (PTSD). Index trauma(s) resulting in PTSD must meet DSM-5 Criterion A for PTSD as described in the CAPS 5, must have occurred within 9 years of Screening Visit 1, and must have occurred when the participant was ≥18 years of age. Willing and able to withdraw and refrain from opioids for the course of the study. Willing to refrain from use of all other formulations of cyclobenzaprine for the course of the study. Willing and able to refrain from antidepressants and other excluded medications. Capable of reading and understanding English and able to provide written informed consent to participate. Willing to comply with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. If female, either not of childbearing potential or practicing a medically acceptable method of birth control throughout the study. Body mass index (BMI) within the range 17.5 - 35 kg/m^2 (inclusive). Exclusion Criteria: Current or ongoing exposure to the trauma that resulted in the PTSD (ie, non-work-related trauma such as ongoing domestic abuse). Increased risk of suicide, based on the investigator's judgment that is of a severity that is not appropriate for outpatient management, or that warrants additional therapy excluded by the protocol. Significant (eg, moderate or severe) comorbid traumatic brain injury (TBI) by history. Severe depressive symptoms at screening or baseline. Clinically significant laboratory abnormalities based on screening laboratory tests and/or medical history in the investigator's opinion. Use of antidepressant medication within 2 months of baseline. Female participants who are pregnant or lactating. History of serotonin syndrome, severe allergic reaction or bronchospasm or known hypersensitivity to cyclobenzaprine or the excipients in TNX-102 SL or placebo formulations. Seizure disorder. Current moderate or severe sleep apnea not well controlled by positive airway pressure (PAP) or oral (mouthpiece) devices. Has received any other investigational drug within 90 days before Screening or has taken cyclobenzaprine within 21 days of the Randomization visit. Previous participation in any other study with TNX-102 SL. Family member of investigative staff.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TNX-102 SL, 5.6 mg<br>2 x TNX-102 SL, 2.8 mg Tablets taken sublingually each day at bedtime for 12 weeks. | Drug: TNX-102 SL<br>* Patients will take 2 tablets of randomly assigned study drug sublingually each day at bedtime starting on Day 1 for 12 weeks<br>* Other names: Low dose cyclobenzaprine sublingual tablets;|
| Placebo Comparator: Placebo<br>2 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks. | Drug: Placebo<br>* Patients will take 2 tablets of randomly assigned study drug sublingually each day at bedtime starting on Day 1 for 12 weeks<br>* Other names: Placebo sublingual tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in the total Clinician Administered PTSD Scale (CAPS-5) for DSM-5 at Week 12. | To evaluate the efficacy of the TNX-102 SL (cyclobenzaprine HCl sublingual tablets) using the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (CAPS-5) total symptom severity score in a 12-week study. | Day 1, Week 4, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression - Severity change from Baseline to Week 12 | CGI-S to assess global severity change from baseline to Week 12 | Day 1, Week 4, Week 8, Week 12 | 
| Change from baseline in the disruption of psychosocial functioning assessed using the Sheehan Disability Scale (SDS) after 12 weeks of treatment. | SDS to assess psychosocial functioning change from baseline to Week 12 | Day 1, Week 4, Week 8, Week 12 |