Open Label Extension Safety and Efficacy Study of TNX-102 SL Tablets in Military Related PTSD and Related Conditions

The study will consist of 4 clinic visits, including Screening/Baseline Visit 1 (Day 0, which is anticipated to be the same date as the final visit in the lead-in P201 study) and visits after 2, 6 and 12 weeks of treatment. The previous requirements in the lead-in study for refraining from the use of certain concomitant medications and trauma-focused psychotherapies will be relaxed. Patients may continue to take rescue therapy for sleep, as appropriate, or they may utilize other medications as needed to help them sleep, per the judgment of the investigator.

Eligible patients who provide written informed consent will take one TNX-102 SL tablet daily at bedtime sublingually (under the tongue) for 12 weeks. All patients will be assigned to receive tthe same dosage of TNX-102 SL, regardless of their treatment assignment in the lead-in study. No patients, investigators, or study staff will know the assigned study treatment from the lead-in study, P201, at the time of entry into the extension study. Patient data collected at the Week 12 visit (Visit 9) in the lead-in P201 study will be used as one of the baseline values for this study.

• TNX-102 SL (Drug), also known as cyclobenzaprine HCI: 1x 2.8mg TNX-102 SL Sublingual tablet

Primary outcomes

• Newly Treatment Emergent Adverse Events [Week 12]: Number of patients with new treatment emergent AEs since completing lead-in study

Secondary outcomes

• Total CAPS-5 (Clinician Administered PTSD Scale (for Diagnostic and Statistical Manual of Mental Disorders Version 5) [P201 Day 1 (12 weeks prior to P202 Day 1), P202 Day 1, P202 Week 12]: Changes in total CAPS-5 score from baseline in lead-in study and since baseline in this study. CAPS-5 score ranges from 0-80 with lower scores indicating less sever PTSD symptoms.
• Response Rates a in Total CAPS-5 Score [P201 Day 1 (12 weeks prior to P202 Day 1), P202 Day 1, P201 Week 12]: ≥30% decrease in Total CAPS-5 score from baseline in lead-in study and since baseline in this study. Lower scores on CAPS-5 indicate less severe PTSD symptoms.
• CAPS-5 Cluster Score Items [P201 Day 1 (12 weeks prior to P202 Day 1), P202 Day 1, P202 Week 12]: Changes from baseline in lead-in study and since baseline in this study in item scores, including * intrusion symptoms (Criterion B) - Score ranges from 0 to 20. * CAPS-5 item 2. (B-2) (unpleasant dreams related to the trauma) - Score ranges from 0 to 4 * persistent avoidance (Criterion C) - Score ranges from 0 to 8 * negative cognitions and mood (Criterion D) - Score ranges from 0 to 28 * arousal and reactivity (Criterion E) - Score ranges from 0 to 24 Lower scores indicate less severe symptoms on all items
• Montgomery-Asberg Depression Rating Scale [P201 Day 1 (12 weeks prior to P202 Day 1), P202 Day 1, P202 Week 12]: Changes from baseline in lead-in study and since baseline in this study in MADRS. Score ranges from 0 to 60. Lower scores indicate less severe depression symptoms.
• PROMIS (Patient -Reported Outcome Measurement Information System) [P201 Day 1 (12 weeks prior to P202 Day 1), P202 Day 1, P202 Week 12]: Changes from baseline in lead-in study and since baseline in this study in PROMIS scores. Raw scores are converted to T-scores with mean of 50 and standard deviation of 10 using published conversion tables based on the US population. * Fatigue T-score ranges from 33.1 to 77.8. Lower scores indicate less fatigue * Sleep Disturbance T-score ranges from 28.9 to 76.5. Lower scores indicate less sleep disturbance * Global Physical Health T-score ranges from 16.2 to 67.7. Lower scores indicate better physical health * Global Mental Health T-score ranges from 21.2 to 67.6. Lower scores indicate better mental health

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Completed the lead-in study and is judged as reasonably compliant, with at least 60% compliance
* Signed informed consent
* Met all prior inclusion and exclusion requirements for lead-in study
* No new or worsening medical conditions since starting the lead-in study that could pose a safety risk or interfere with participation in the study
* Willing to refrain from use of specific medication (ask PI)
* Female patients of childbearing potential continue to practice medically acceptable methods of birth control

Exclusion Criteria:

* None

Participant flow

Outcome results

• Newly Treatment Emergent Adverse Events (Primary), Count of participants, Participants: Placebo- TNX-102 SL 2.8 mg 37; TNX 102 SL 2.8 mg - TNX-102 SL 2.8 mg 20; TNX-102 SL 5.6 mg - TNX-102 SL 2.8 mg 14
• Total CAPS-5 (Clinician Administered PTSD Scale (for Diagnostic and Statistical Manual of Mental Disorders Version 5) (Secondary), Least squares mean, units on a scale: Placebo- TNX-102 SL 2.8 mg -25.3 +/- 2.55; TNX 102 SL 2.8 mg - TNX-102 SL 2.8 mg -25.6 +/- 2.59; TNX-102 SL 5.6 mg - TNX-102 SL 2.8 mg -26.9 +/- 2.80
• Response Rates a in Total CAPS-5 Score (Secondary), Count of participants, Participants: Placebo- TNX-102 SL 2.8 mg 43; TNX 102 SL 2.8 mg - TNX-102 SL 2.8 mg 47; TNX-102 SL 5.6 mg - TNX-102 SL 2.8 mg 30
• CAPS-5 Cluster Score Items (Secondary), Least squares mean, units on a scale: Placebo- TNX-102 SL 2.8 mg -7.7 +/- 0.82; TNX 102 SL 2.8 mg - TNX-102 SL 2.8 mg -7.4 +/- 0.82; TNX-102 SL 5.6 mg - TNX-102 SL 2.8 mg -7.7 +/- 0.91
• Montgomery-Asberg Depression Rating Scale (Secondary), Least squares mean, units on a scale: Placebo- TNX-102 SL 2.8 mg -8.1 +/- 1.53; TNX 102 SL 2.8 mg - TNX-102 SL 2.8 mg -9.3 +/- 1.57; TNX-102 SL 5.6 mg - TNX-102 SL 2.8 mg -9.9 +/- 1.66
• PROMIS (Patient -Reported Outcome Measurement Information System) (Secondary), Least squares mean, T-score: Placebo- TNX-102 SL 2.8 mg -10.4 +/- 2.50; TNX 102 SL 2.8 mg - TNX-102 SL 2.8 mg -12.2 +/- 2.58; TNX-102 SL 5.6 mg - TNX-102 SL 2.8 mg -14.3 +/- 2.75

Adverse events

Time frame: 12 Weeks

Other adverse events by term

• Denise Bedoya, Study director, Premier Research