Fibromyalgia, Muscular Diseases, Musculoskeletal Diseases, Myofascial Pain Syndromes, Nervous System Diseases, Neuromuscular Diseases, Rheumatic Diseases
Conditions
Keywords
Pain, Sleep
Brief summary
The use of low-dose CBP dosed nightly at bedtime for FM was supported by the results of Tonix' TNX-CY-F202 Phase 2b study (also referred to as the BESTFIT Study). The TNX-CY-F202 study provided evidence that TNX-102 SL 2.8 mg dosed nightly results in beneficial effects upon pain, sleep and other FM symptomatology. The present trial is designed to assess the safety and efficacy of TNX-102 SL 2.8 mg tablets, taken daily at bedtime over 12 weeks to treat fibromyalgia.
Interventions
DRUGTNX-102 SL Tablet, 2.8mg
Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 1 for 12 weeks.
Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 1 for 12 weeks.
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Primary Fibromyalgia (2010 ACR criteria) * Male or female 18-75 years old * For patients with major depressive disorders only: clinically stable, no suicidal risk and stable anti-depressant therapy * Willing and able to withdraw specific therapies (ask PI) * Medically acceptable form of contraception (female only) * Signed informed consent
Exclusion criteria
* Arthritis, lupus and other systemic auto-immune diseases * Regional or persistent pain that could interfere with assessment of fibromyalgia pain * Bipolar and psychotic disorders * Increased risk of suicide * Significant clinical (cardiac, systemic infection, systemic corticosteroid requirement, drug/alcohol abuse) or laboratory abnormalities. * Inability to wash-out specific medications (ask PI) * Known hypersensitivity to cyclobenzaprine * Others: seizure disorders, severe/untreated sleep apnea, BMI\>40
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With ≥30% Pain Improvement | Day 1, Week 12 | The primary efficacy endpoint is the proportion of patients with a ≥30% improvement (responder criteria) from baseline to Week 12 in the weekly mean of the daily self-reported 24-hour recall average pain intensity score using an 11-point (0-10) NRS. Scores range from 0 (no pain) to 10 (worst possible pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in the Fibromyalgia Impact Questionnaire - Revised (FIQR) Symptoms Domain Score | Day 1, Week 12 | The FIQR is a validated questionnaire. Scores on the symptoms domain range from 0 to 100 where a higher score means worse outcome. |
| Change From Baseline to Week 12 in the FIQR Function Domain Score | Day 1, Week 12 | The FIQR is a validated questionnaire. Scores on the function domain range from 0 to 90 where a higher score means worse outcome. |
| Patient Reported Outcomes Measurement System (PROMIS) Sleep Disturbance | Day 1, Week 12 | Change from baseline in the PROMIS score for sleep disturbance at Week 12. The PROMIS Sleep disturbance short form 8a consists of 8 questions on a 5-point scale (1 to 5) where a higher score indicates a worse outcome. The total score is reported on a range of 8 to 40. Raw scores are converted to T-scores based on US population with score of 50 as average with a standard deviation of 10. Lower T-scores indicate less sleep disturbance. |
| Patient's Global Impression of Change (PGIC) | Week 12 | Proportion of patients with a PGIC rating of 1 (very much improved) or 2 (much improved) at Week 12. The PGIC is a fibromyalgia specific validated instrument on a scale of 1 to 7, where a score of 1 indicates the highest level of improvement and a score of 7 indicates the highest level of worsening. |
| Patient Reported Outcomes Measurement System (PROMIS) Fatigue | Day 1, Week 12 | Change from Baseline in the PROMIS score for fatigue at Week 12. The PROMIS fatigue short form 8a consists of 8 questions on a 5 point scale (1 to 5) where a higher score indicates a worse outcome. The total score is reported on a range of 8 to 40. Raw scores are converted to T-scores based on US population with score of 50 as average with a standard deviation of 10. Lower T-scores indicate less fatigue. |
| Weekly Average of Daily Pain Diary | Baseline (Day -7 to Day -1), Week 12 | Change from baseline to Week 12 in the weekly average of the daily self-reported average pain severity score using an 11-point (0-10) NRS. Scores range from 0 (no pain) to 10 (worst possible pain). |
| Weekly Average of Daily Sleep Quality Diary | Baseline (Day -7 to Day -1), Week 12 | Change from Baseline in the weekly average of the daily diary assessment of sleep quality at Week 12. Patients provide a daily numeric assessment of their sleep quality for the previous night, via an electronic diary, using an 11-point NRS. Scores range from 0 (best possible sleep) to 10 (worst possible sleep). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo SL Tablet 1 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks
Placebo SL Tablet: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 1 for 12 weeks. | 257 |
| TNX-102 SL Tablet, 2.8 mg 1 x TNX-102 SL 2.8mg Tablet taken sublingually each day at bedtime for 12 weeks
TNX-102 SL Tablet, 2.8mg: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 1 for 12 weeks. | 262 |
| Total | 519 |
Baseline characteristics
| Characteristic | Placebo SL Tablet | Total | TNX-102 SL Tablet, 2.8 mg |
|---|---|---|---|
| Age, Continuous | 47.8 years STANDARD_DEVIATION 11.2 | 47.8 years STANDARD_DEVIATION 11.17 | 47.8 years STANDARD_DEVIATION 11.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 52 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 236 Participants | 467 Participants | 231 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants | 38 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 221 Participants | 463 Participants | 242 Participants |
| Region of Enrollment United States | 257 participants | 519 participants | 262 participants |
| Sex: Female, Male Female | 247 Participants | 499 Participants | 252 Participants |
| Sex: Female, Male Male | 10 Participants | 20 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 256 | 0 / 262 |
| other Total, other adverse events | 17 / 256 | 132 / 262 |
| serious Total, serious adverse events | 4 / 256 | 3 / 262 |
Outcome results
Primary
Proportion of Patients With ≥30% Pain Improvement
The primary efficacy endpoint is the proportion of patients with a ≥30% improvement (responder criteria) from baseline to Week 12 in the weekly mean of the daily self-reported 24-hour recall average pain intensity score using an 11-point (0-10) NRS. Scores range from 0 (no pain) to 10 (worst possible pain).
Time frame: Day 1, Week 12
Population: Results are reported for the ITT population which includes all patients who were randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo SL Tablet | Proportion of Patients With ≥30% Pain Improvement | 58 Participants |
| TNX-102 SL Tablet, 2.8 mg | Proportion of Patients With ≥30% Pain Improvement | 75 Participants |
Secondary
Change From Baseline to Week 12 in the Fibromyalgia Impact Questionnaire - Revised (FIQR) Symptoms Domain Score
The FIQR is a validated questionnaire. Scores on the symptoms domain range from 0 to 100 where a higher score means worse outcome.
Time frame: Day 1, Week 12
Population: Results are reported for the ITT population which includes all patients who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SL Tablet | Change From Baseline to Week 12 in the Fibromyalgia Impact Questionnaire - Revised (FIQR) Symptoms Domain Score | -8.2 units on a scale | Standard Error 1.13 |
| TNX-102 SL Tablet, 2.8 mg | Change From Baseline to Week 12 in the Fibromyalgia Impact Questionnaire - Revised (FIQR) Symptoms Domain Score | -14.1 units on a scale | Standard Error 1.14 |
Secondary
Change From Baseline to Week 12 in the FIQR Function Domain Score
The FIQR is a validated questionnaire. Scores on the function domain range from 0 to 90 where a higher score means worse outcome.
Time frame: Day 1, Week 12
Population: Results are reported for the ITT population which includes all patients who were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SL Tablet | Change From Baseline to Week 12 in the FIQR Function Domain Score | -4.4 units on a scale | Standard Error 1.15 |
| TNX-102 SL Tablet, 2.8 mg | Change From Baseline to Week 12 in the FIQR Function Domain Score | -10.3 units on a scale | Standard Error 1.16 |
Secondary
Patient Reported Outcomes Measurement System (PROMIS) Fatigue
Change from Baseline in the PROMIS score for fatigue at Week 12. The PROMIS fatigue short form 8a consists of 8 questions on a 5 point scale (1 to 5) where a higher score indicates a worse outcome. The total score is reported on a range of 8 to 40. Raw scores are converted to T-scores based on US population with score of 50 as average with a standard deviation of 10. Lower T-scores indicate less fatigue.
Time frame: Day 1, Week 12
Population: Results are reported for the ITT population which includes all patients who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SL Tablet | Patient Reported Outcomes Measurement System (PROMIS) Fatigue | -4.2 T-score | Standard Error 0.47 |
| TNX-102 SL Tablet, 2.8 mg | Patient Reported Outcomes Measurement System (PROMIS) Fatigue | -6.4 T-score | Standard Error 0.47 |
Secondary
Patient Reported Outcomes Measurement System (PROMIS) Sleep Disturbance
Change from baseline in the PROMIS score for sleep disturbance at Week 12. The PROMIS Sleep disturbance short form 8a consists of 8 questions on a 5-point scale (1 to 5) where a higher score indicates a worse outcome. The total score is reported on a range of 8 to 40. Raw scores are converted to T-scores based on US population with score of 50 as average with a standard deviation of 10. Lower T-scores indicate less sleep disturbance.
Time frame: Day 1, Week 12
Population: Results are reported for the ITT population which includes all patients who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SL Tablet | Patient Reported Outcomes Measurement System (PROMIS) Sleep Disturbance | -4.7 T-score | Standard Error 0.53 |
| TNX-102 SL Tablet, 2.8 mg | Patient Reported Outcomes Measurement System (PROMIS) Sleep Disturbance | -8.0 T-score | Standard Error 0.54 |
Secondary
Patient's Global Impression of Change (PGIC)
Proportion of patients with a PGIC rating of 1 (very much improved) or 2 (much improved) at Week 12. The PGIC is a fibromyalgia specific validated instrument on a scale of 1 to 7, where a score of 1 indicates the highest level of improvement and a score of 7 indicates the highest level of worsening.
Time frame: Week 12
Population: Results are reported for the ITT population which includes all patients who were randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo SL Tablet | Patient's Global Impression of Change (PGIC) | 42 Participants |
| TNX-102 SL Tablet, 2.8 mg | Patient's Global Impression of Change (PGIC) | 62 Participants |
Secondary
Weekly Average of Daily Pain Diary
Change from baseline to Week 12 in the weekly average of the daily self-reported average pain severity score using an 11-point (0-10) NRS. Scores range from 0 (no pain) to 10 (worst possible pain).
Time frame: Baseline (Day -7 to Day -1), Week 12
Population: Results are reported for the ITT population which includes all patients who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SL Tablet | Weekly Average of Daily Pain Diary | -1.0 units on a scale | Standard Error 0.11 |
| TNX-102 SL Tablet, 2.8 mg | Weekly Average of Daily Pain Diary | -1.5 units on a scale | Standard Error 0.11 |
Secondary
Weekly Average of Daily Sleep Quality Diary
Change from Baseline in the weekly average of the daily diary assessment of sleep quality at Week 12. Patients provide a daily numeric assessment of their sleep quality for the previous night, via an electronic diary, using an 11-point NRS. Scores range from 0 (best possible sleep) to 10 (worst possible sleep).
Time frame: Baseline (Day -7 to Day -1), Week 12
Population: Results are reported for the ITT population which includes all patients who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SL Tablet | Weekly Average of Daily Sleep Quality Diary | -1.0 units on a scale | Standard Error 0.11 |
| TNX-102 SL Tablet, 2.8 mg | Weekly Average of Daily Sleep Quality Diary | -1.8 units on a scale | Standard Error 0.11 |