Safety and Efficacy Study of TNX-102 SL in Patients With Military-related PTSD (HONOR)

• ClinicalTrials.gov Identifier: NCT03062540
• Recruitment Status: Terminated
• First Posted: February 23, 2017
• Last Update Posted: September 17, 2019
• Sponsor: Tonix Pharmaceuticals, Inc.
• Collaborator: Premier Research Group plc
• Information provided by (Responsible Party): Tonix Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: February 20, 2017
• First Posted Date: February 23, 2017
• Last Update Posted Date: September 17, 2019
• Actual Study Start Date: March 27, 2017
• Actual Primary Completion Date: July 27, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 23, 2017)

Mean change from baseline in the total Clinician Administered PTSD Scale (CAPS-5) for DSM-5 at Week 12. [ Time Frame: Day 0, Week 4, Week 8 and 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.

• Original Primary Outcome Measures (submitted: February 20, 2017): Mean change from baseline in the total Clinician Administered PTSD Scale (CAPS-5) for DSM-5 at Week 12 [ Time Frame: 12 weeks ]

Current Secondary Outcome Measures (submitted: February 23, 2017)

• Clinical Global Impression - Improvement from Initiation of Treatment (CGI-I) score after 12 weeks of treatment. [ Time Frame: 12 weeks ]
  To evaluate the efficacy of the TNX-102 SL (cyclobenzaprine HCl sublingual tablets) using the CGI-I score after 12 weeks of treatment.
• Change from baseline in the disruption of social life/leisure activities assessed using the Sheehan Disability Scale (SDS) after 12 weeks of treatment. [ Time Frame: Day 0, Week 4, Week 8 and Week 12. ]
  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.
• Change from baseline in the disruption of work/school activities assessed using the Sheehan Disability Scale (SDS) after 12 weeks of treatment. [ Time Frame: Day 0, Week 4, Week 8 and Week 12. ]
  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.
• 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. [ Time Frame: Day 0, Week 4, Week 8 and Week 12. ]
  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.

Original Secondary Outcome Measures (submitted: February 20, 2017)

• CGI-I score after 12 weeks of treatment. [ Time Frame: 12 weeks ]
• Change from baseline in the disruption of social life/leisure activities assessed using the SDS after 12 weeks of treatment [ Time Frame: 12 weeks ]
• Change from baseline in the disruption of work/school activities assessed using the SDS after 12 weeks of treatment. [ Time Frame: 12 weeks ]
• Change from baseline in patients' quality of sleep using the PROMIS Sleep Disturbance scale after 12 weeks of treatment [ Time Frame: 12 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy Study of TNX-102 SL in Patients With Military-related PTSD
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: PTSD

Intervention

• Drug: TNX-102 SL
  Patients will take 2 tablets of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks
  Other Name: Low dose cyclobenzaprine sublingual tablets
• Drug: Placebo SL Tablet
  Patients will take 2 tablets of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks
  Other Name: Placebo sublingual tablets

Study Arms

• Experimental: TNX-102 SL Tablet, 2.8 mg
  2 x TNX-102 SL, 2.8 mg Tablets taken sublingually each day at bedtime for 12 weeks.
  Intervention: Drug: TNX-102 SL
• Placebo Comparator: Placebo SL Tablet
  2 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks.
  Intervention: Drug: Placebo SL Tablet

• Publications *: Dunlop BW, Rakofsky JJ, Newport DJ, Mletzko-Crowe T, Barone K, Nemeroff CB, Harvey PD. Efficacy of Vortioxetine Monotherapy for Posttraumatic Stress Disorder: A Randomized, Placebo-Controlled Trial. J Clin Psychopharmacol. 2021 Mar-Apr 01;41(2):172-179. doi: 10.1097/JCP.0000000000001363.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 27, 2018): 358
• Original Estimated Enrollment (submitted: February 20, 2017): 550
• Actual Study Completion Date: July 27, 2018
• Actual Primary Completion Date: July 27, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03062540
• Other Study ID Numbers: TNX-CY-P301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Tonix Pharmaceuticals, Inc.
• Study Sponsor: Tonix Pharmaceuticals, Inc.
• Collaborators: Premier Research Group plc

Investigators

• Study Director: Greg Sullivan, MD; Tonix Pharmaceuticals

• PRS Account: Tonix Pharmaceuticals, Inc.
• Verification Date: September 2019