Safety and Efficacy Study of TNX-102 SL in Patients With Military-related 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 3, Double-Blind, Randomized, Multicenter, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TNX-102 SL Taken Daily at Bedtime in Patients With Military-Related PTSD

Conditions
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PTSD

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between 18 and 75 years of age, who have served in any branch of the military. Diagnosed with current PTSD as determined by the Clinician-Administered PTSD Scale (CAPS-5) for DSM-5. Index trauma(s) resulting in PTSD must meet DSM-5 criterion A for PTSD as described in CAPS-5, have occurred in 2001 or later, be military service related. Willing to refrain from use of all other formulations of cyclobenzaprine. Willing and able to refrain from antidepressants and other excluded medications. Capable of reading and understanding English and able to provide written informed consent. If female, either not of childbearing potential or practicing a medically acceptable method of birth control throughout the study. Willing and able to comply with all protocol-specified requirements. Exclusion Criteria: 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 (e.g., 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 patients who are pregnant or lactating. History of serotonin syndrome, severe allergic reaction or bronchospasm or known hypersensitivity to cyclobenzaprine or the excipients. Seizure disorder. Patients with a body mass index (BMI) > 45. Has received any other investigational drug within 30 days before Screening. 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 Tablet, 2.8 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 0 for 12 weeks<br>* Other names: Low dose cyclobenzaprine sublingual tablets;|
| Placebo Comparator: Placebo SL Tablet<br>2 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks. | Drug: Placebo SL Tablet<br>* Patients will take 2 tablets of randomly assigned study drug sublingually each day at bedtime starting on Day 0 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 (DSM-5) (CAPS-5) total symptom severity score in a 12-week study. | Day 0, Week 4, Week 8 and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression - Improvement from Initiation of Treatment (CGI-I) score after 12 weeks of treatment. | To evaluate the efficacy of the TNX-102 SL (cyclobenzaprine HCl sublingual tablets) using the CGI-I score after 12 weeks of treatment. | 12 weeks | 
| Change from baseline in the disruption of social life/leisure activities assessed using the Sheehan Disability Scale (SDS) after 12 weeks of treatment. | To evaluate the efficacy of the TNX-102 SL (cyclobenzaprine HCl sublingual tablets) using the change from baseline in disruption of social life/leisure activities assessed with the SDS after 12 weeks of treatment. | Day 0, Week 4, Week 8 and Week 12. | 
| Change from baseline in the disruption of work/school activities assessed using the Sheehan Disability Scale (SDS) after 12 weeks of treatment. | To evaluate the efficacy of the TNX-102 SL (cyclobenzaprine HCl sublingual tablets) using the change from baseline in disruption of work/school activities assessed with the SDS after 12 weeks of treatment. | Day 0, Week 4, Week 8 and Week 12. | 
| Change from baseline in patients' quality of sleep using the Patient-Reported Outcome Measurement Information System (PROMIS) Sleep Disturbance scale after 12 weeks of treatment. | To evaluate the efficacy of the TNX-102 SL (cyclobenzaprine HCl sublingual tablets) using the change from baseline in quality of sleep using the PROMIS Sleep Disturbance scale after 12 weeks of treatment. | Day 0, Week 4, Week 8 and Week 12. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PTSD, Military-related PTSD