PTSD
Conditions
Keywords
PTSD, Military-related PTSD and other related conditions
Brief summary
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.
Interventions
DRUGTNX-102 SL
DRUGPlacebo
Sponsors
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 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Change From Baseline (Visit 2) in the Total CAPS-5 Score After 12 Weeks of Treatment Evaluated at Visit 9 (Week 12). | Day 1, Week 12 | The mean change from baseline (Visit 2) in the Total CAPS-5 score after 12 weeks of treatment evaluated at Visit 9 (Week 12). The primary efficacy comparison will be the change from baseline in total CAPS-5 score for the 2.8 mg treatment arm compared to placebo. CAPS-5 score ranges from 0-80 with lower scores indicating less severe PTSD symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Patients' Quality of Sleep Using the PROMIS Sleep Disturbance Scale After 12 Weeks of Treatment | Day 1, Week 12 | Change from baseline in patients' quality of sleep using the PROMIS (Patient -Reported Outcome Measurement Information System) Sleep Disturbance scale after 12 weeks of treatment comparing the 2.8 mg treatment arm to placebo. Raw scores are converted to T-scores using published conversion tables. Sleep Disturbance T-score ranges from 28.9 to 76.5. Lower scores indicate less sleep disturbance |
| Clinician Global Impression - Improvement Scale Responder Rate at Week 12 | Week 12 | Responder rates in CGI-I (Clinician Global Impression - Improvement Scale) after 12 weeks of treatment comparing the 2.8 mg treatment arm to placebo. Responder rate is defined as the number of patients scored as either a 1 or 2 on CGI-I at Week 12. The score ranges from 1 to 7 with the following anchors for each score:1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse, 7=Very much worse |
| Mean Change From Baseline in Sheehan Disability Scale (SDS) Total Score | Day 1, Week 12 | Mean Change from Baseline in SDS Total Score at Week 12. Score ranges from 0 to 30. A score of 0 means the patient is unimpaired, and a score of 30 means the patient is highly impaired. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 2 x placebo tablet (placebo) to be taken sublingually once daily at bedtime. | 94 |
| TNX-102 SL, 2.8 mg 1 x TNX-102 SL 2.8 mg tablet (TNX-102 SL) and 1 x placebo tablet (placebo) to be taken sublingually once daily at bedtime. | 101 |
| TNX-102 SL, 5.6 mg 2 x TNX-102 SL 2.8mg tablets (TNX-102 SL) to be taken sublingually once daily at bedtime. | 50 |
| Total | 245 |
Baseline characteristics
| Characteristic | Placebo | TNX-102 SL, 2.8 mg | TNX-102 SL, 5.6 mg | Total |
|---|---|---|---|---|
| Age, Continuous Age | 31.9 years STANDARD_DEVIATION 6.48 | 34.5 years STANDARD_DEVIATION 8.11 | 34.7 years STANDARD_DEVIATION 8.93 | 33.6 years STANDARD_DEVIATION 7.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 15 Participants | 11 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants | 86 Participants | 39 Participants | 199 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 27 Participants | 12 Participants | 60 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 1 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 1 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) White | 61 Participants | 68 Participants | 33 Participants | 162 Participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 4 Participants | 19 Participants |
| Sex: Female, Male Male | 88 Participants | 92 Participants | 46 Participants | 226 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 94 | 0 / 101 | 0 / 50 |
| other Total, other adverse events | 36 / 94 | 59 / 93 | 35 / 50 |
| serious Total, serious adverse events | 3 / 94 | 0 / 93 | 1 / 50 |
Outcome results
Primary
The Mean Change From Baseline (Visit 2) in the Total CAPS-5 Score After 12 Weeks of Treatment Evaluated at Visit 9 (Week 12).
The mean change from baseline (Visit 2) in the Total CAPS-5 score after 12 weeks of treatment evaluated at Visit 9 (Week 12). The primary efficacy comparison will be the change from baseline in total CAPS-5 score for the 2.8 mg treatment arm compared to placebo. CAPS-5 score ranges from 0-80 with lower scores indicating less severe PTSD symptoms.
Time frame: Day 1, Week 12
Population: Results are reported for patients in mITT population (included all patients who were randomized, had a baseline CAPS-5 and at least one post-baseline CAPS-5).~At Week 12 or last visit for subjects discontinuing early, values recorded more than 7 days after the last recorded dose are censored. Subjects that are lost to follow up or do not have a last dose date recorded have the day before their final visit imputed as the last dose date.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | The Mean Change From Baseline (Visit 2) in the Total CAPS-5 Score After 12 Weeks of Treatment Evaluated at Visit 9 (Week 12). | -17.0 units on a scale | Standard Error 1.98 |
| TNX-102 SL, 2.8 mg | The Mean Change From Baseline (Visit 2) in the Total CAPS-5 Score After 12 Weeks of Treatment Evaluated at Visit 9 (Week 12). | -19.2 units on a scale | Standard Error 1.99 |
| TNX-102 SL, 5.6 mg | The Mean Change From Baseline (Visit 2) in the Total CAPS-5 Score After 12 Weeks of Treatment Evaluated at Visit 9 (Week 12). | -21.5 units on a scale | Standard Error 2.41 |
Secondary
Change From Baseline in Patients' Quality of Sleep Using the PROMIS Sleep Disturbance Scale After 12 Weeks of Treatment
Change from baseline in patients' quality of sleep using the PROMIS (Patient -Reported Outcome Measurement Information System) Sleep Disturbance scale after 12 weeks of treatment comparing the 2.8 mg treatment arm to placebo. Raw scores are converted to T-scores using published conversion tables. Sleep Disturbance T-score ranges from 28.9 to 76.5. Lower scores indicate less sleep disturbance
Time frame: Day 1, Week 12
Population: Results are reported for patients in mITT population (included all patients who were randomized, had a baseline CAPS-5 and at least one post-baseline CAPS-5).~At Week 12 or last visit for subjects discontinuing early, values recorded more than 7 days after the last recorded dose are censored. Subjects that are lost to follow up or do not have a last dose date recorded have the day before their final visit imputed as the last dose date.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patients' Quality of Sleep Using the PROMIS Sleep Disturbance Scale After 12 Weeks of Treatment | -7.9 units on a scale | Standard Error 1.72 |
| TNX-102 SL, 2.8 mg | Change From Baseline in Patients' Quality of Sleep Using the PROMIS Sleep Disturbance Scale After 12 Weeks of Treatment | -11.1 units on a scale | Standard Error 1.74 |
| TNX-102 SL, 5.6 mg | Change From Baseline in Patients' Quality of Sleep Using the PROMIS Sleep Disturbance Scale After 12 Weeks of Treatment | -11.0 units on a scale | Standard Error 2.1 |
Secondary
Clinician Global Impression - Improvement Scale Responder Rate at Week 12
Responder rates in CGI-I (Clinician Global Impression - Improvement Scale) after 12 weeks of treatment comparing the 2.8 mg treatment arm to placebo. Responder rate is defined as the number of patients scored as either a 1 or 2 on CGI-I at Week 12. The score ranges from 1 to 7 with the following anchors for each score: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
Population: Results are reported for patients in mITT population (included all patients who were randomized, had a baseline CAPS-5 and at least one post-baseline CAPS-5). Patients without CGI-I data at Week 12 were considered as being non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Clinician Global Impression - Improvement Scale Responder Rate at Week 12 | 41 Participants |
| TNX-102 SL, 2.8 mg | Clinician Global Impression - Improvement Scale Responder Rate at Week 12 | 48 Participants |
| TNX-102 SL, 5.6 mg | Clinician Global Impression - Improvement Scale Responder Rate at Week 12 | 31 Participants |
Secondary
Mean Change From Baseline in Sheehan Disability Scale (SDS) Total Score
Mean Change from Baseline in SDS Total Score at Week 12. Score ranges from 0 to 30. A score of 0 means the patient is unimpaired, and a score of 30 means the patient is highly impaired.
Time frame: Day 1, Week 12
Population: Results are reported for patients in mITT population (included all patients who were randomized, had a baseline CAPS-5 and at least one post-baseline CAPS-5).~At Week 12 or last visit for subjects discontinuing early, values recorded more than 7 days after the last recorded dose are censored. Subjects that are lost to follow up or do not have a last dose date recorded have the day before their final visit imputed as the last dose date.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Sheehan Disability Scale (SDS) Total Score | -6.4 units on a scale | Standard Error 1.11 |
| TNX-102 SL, 2.8 mg | Mean Change From Baseline in Sheehan Disability Scale (SDS) Total Score | -7.9 units on a scale | Standard Error 1.11 |
| TNX-102 SL, 5.6 mg | Mean Change From Baseline in Sheehan Disability Scale (SDS) Total Score | -8.7 units on a scale | Standard Error 1.35 |