Safety and Efficacy Study of TNX-102 SL in Subjects With Military-Related PTSD and Related Conditions

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, parallel-group study that will investigate the efficacy and safety of two doses of TNX-102 SL -a sublingual formulation of cyclobenzaprine. Following successful screening and randomization, eligible subjects will return regularly to the study clinic for weekly or biweekly 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 TNX-102 SL Taken at Bedtime in Subjects With Military-Related PTSD and Related Conditions (Protocol No. TNX-CY-P201) -AtEase STUDY

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 65 years of age Diagnosed with current PTSD as defined by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), For patients with a qualifying Index trauma(s) resulting in PTSD that occurred during military service, military contractor, Department of Homeland Security or law enforcement Willing and able to withdraw and refrain from specific therapies (ask PI) Use medically acceptable form of contraception (female only) Signed informed consent Exclusion Criteria: Significant traumatic brain injury Severe depression Bipolar and psychotic disorders Increase risk of suicide Significant clinical (cardiac, systemic infection, drug/alcohol abuse) or laboratory abnormalities (including positivity for Hep B, Hep C, HIV) Unable to wash-out specific medications (ask PI) History of violent behavior within past 2 years, unrelated to work duties History of drug or alcohol abuse within past 6 months Positive illegal substance test Known hypersensitivity to cyclobenzaprine Others: seizure disorders, uncontrolled sleep apnea, BMI>40 Participation in an investigational study in past 30 days In the process of litigating for compensation for a psychiatric disorder Females that are pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Placebo Comparator: Treatment A<br>2 x placebo tablet (placebo) to be taken sublingually once daily at bedtime. | Drug: Placebo<br> <br> |
| Active Comparator: Treatment B<br>1 x TNX-102 SL 2.8mg tablet (TNX-102 SL) and 1 x placebo tablet (placebo) to be taken sublingually once daily at bedtime. | Drug: TNX-102 SL<br> <br> Drug: Placebo<br> <br> |
| Active Comparator: Treatment C<br>2 x TNX-102 SL 2.8mg tablets (TNX-102 SL) to be taken sublingually once daily at bedtime. | Drug: TNX-102 SL<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the efficacy of TNX-102 SL 2.8 mg using the DSM-5 total symptom severity score | 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. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinician Administered PTSD Scale (for DSM-5) |  | Continuously throughout the treatment period (total duration: about 3 months) | 
| PTSD Checklist (Version 5) |  | Continuously throughout the treatment period (total duration: about 3 months) | 
| Sheehan Disability Scale |  | Continuously throughout the treatment period (total duration: about 3 months) | 
| Patient Global Impression of Change (Since Baseline) Scale |  | Continuously throughout the treatment period (total duration: about 3 months) | 
| Number of Participants with Adverse Events |  | Continuously throughout the treatment period (total duration: about 3 months) | 
| Change from baseline in ECG, lab results, vital signs and weight |  | Baseline and week 12 | 
| Changes from baseline in subject reported morning sedation |  | Baseline, and weeks 2, 4, 8, and 12 | 
| Changes from baseline indicative of increased suicidal ideation or behavior as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) |  | Baseline, and weeks 1, 2, 4, 6, 8, and 12 | 
| Patient-Reported Outcome Measurement Information System- Sleep |  | Continuously throughout the treatment period (total duration: about 3 months) | 

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