PTSD
Conditions
Keywords
PTSD, 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.
Interventions
DRUGTNX-102 SL
Patients will take 2 tablets of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks
Patients will take 2 tablets of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks
Sponsors
Premier Research
Tonix Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Total Clinician Administered PTSD Scale (CAPS-5) for DSM-5 at Week 12. | Day 0 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. Score ranges from 0 to 80 with lower scores indicating less severe PTSD symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Improvement From Initiation of Treatment (CGI-I) Score After 12 Weeks of Treatment. | Week 12 | To evaluate the efficacy of the TNX-102 SL (cyclobenzaprine HCl sublingual tablets) using the CGI-I score after 12 weeks of treatment. Score ranges from 1 to 7. 1 = Very much improved. 2 = Much improved. 3 = Minimally improved. 4 = No change. 5 = Minimally worse. 6 = Much worse. 7 = Very much worse. |
| Change From Baseline in the Disruption of Social Life/Leisure Activities Assessed Using the Sheehan Disability Scale (SDS) After 12 Weeks of Treatment. | Day 0, 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. Score ranges from 0 to 10. Lower scores indicate less disruption to social life/leisure activities. |
| Change From Baseline in the Disruption of Work/School Activities Assessed Using the Sheehan Disability Scale (SDS) After 12 Weeks of Treatment. | Day 0, 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. Score ranges from 0 to 10. Lowers scores indicate less disruption to work/school activities. |
| 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. | Day 0, 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. Raw score is transformed to T-scores using published conversions. T-score ranges from 30 to 80 with lower scores indicating better sleep quality. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TNX-102 SL Tablet, 5.6 mg 2 x TNX-102 SL, 2.8 mg Tablets taken sublingually each day at bedtime for 12 weeks.
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 | 179 |
| Placebo SL Tablet 2 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks.
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 | 179 |
| Total | 358 |
Baseline characteristics
| Characteristic | TNX-102 SL Tablet, 5.6 mg | Total | Placebo SL Tablet |
|---|---|---|---|
| Age, Continuous | 35.4 years STANDARD_DEVIATION 8.21 | 35.7 years STANDARD_DEVIATION 7.95 | 35.9 years STANDARD_DEVIATION 7.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 69 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 144 Participants | 289 Participants | 145 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 13 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants | 62 Participants | 31 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 10 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 12 Participants | 5 Participants |
| Race (NIH/OMB) White | 122 Participants | 246 Participants | 124 Participants |
| Region of Enrollment United States | 179 participants | 358 participants | 179 participants |
| Sex: Female, Male Female | 15 Participants | 36 Participants | 21 Participants |
| Sex: Female, Male Male | 164 Participants | 322 Participants | 158 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 179 | 0 / 179 |
| other Total, other adverse events | 93 / 175 | 21 / 176 |
| serious Total, serious adverse events | 3 / 175 | 5 / 176 |
Outcome results
Primary
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. Score ranges from 0 to 80 with lower scores indicating less severe PTSD symptoms.
Time frame: Day 0 and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Mean Change From Baseline in the Total Clinician Administered PTSD Scale (CAPS-5) for DSM-5 at Week 12. | -15.2 units on a scale | Standard Error 1.9 |
| Placebo SL Tablet | Mean Change From Baseline in the Total Clinician Administered PTSD Scale (CAPS-5) for DSM-5 at Week 12. | -14.2 units on a scale | Standard Error 1.8 |
Secondary
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. Raw score is transformed to T-scores using published conversions. T-score ranges from 30 to 80 with lower scores indicating better sleep quality.
Time frame: Day 0, Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | 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. | -9.3 units on a scale | Standard Error 1.6 |
| Placebo SL Tablet | 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. | -6.7 units on a scale | Standard Error 1.49 |
Secondary
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. Score ranges from 0 to 10. Lower scores indicate less disruption to social life/leisure activities.
Time frame: Day 0, Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Change From Baseline in the Disruption of Social Life/Leisure Activities Assessed Using the Sheehan Disability Scale (SDS) After 12 Weeks of Treatment. | -2.1 units on a scale | Standard Error 0.38 |
| Placebo SL Tablet | Change From Baseline in the Disruption of Social Life/Leisure Activities Assessed Using the Sheehan Disability Scale (SDS) After 12 Weeks of Treatment. | -1.7 units on a scale | Standard Error 0.35 |
Secondary
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. Score ranges from 0 to 10. Lowers scores indicate less disruption to work/school activities.
Time frame: Day 0, Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Change From Baseline in the Disruption of Work/School Activities Assessed Using the Sheehan Disability Scale (SDS) After 12 Weeks of Treatment. | -1.6 units on a scale | Standard Error 0.46 |
| Placebo SL Tablet | Change From Baseline in the Disruption of Work/School Activities Assessed Using the Sheehan Disability Scale (SDS) After 12 Weeks of Treatment. | -1.3 units on a scale | Standard Error 0.41 |
Secondary
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. Score ranges from 1 to 7. 1 = Very much improved. 2 = Much improved. 3 = Minimally improved. 4 = No change. 5 = Minimally worse. 6 = Much worse. 7 = Very much worse.
Time frame: Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Clinical Global Impression - Improvement From Initiation of Treatment (CGI-I) Score After 12 Weeks of Treatment. | 2.6 score on a scale | Standard Error 0.16 |
| Placebo SL Tablet | Clinical Global Impression - Improvement From Initiation of Treatment (CGI-I) Score After 12 Weeks of Treatment. | 2.7 score on a scale | Standard Error 0.15 |