Fibromyalgia, Muscular Diseases, Musculoskeletal Diseases, Myofascial Pain Syndromes, Nervous System Diseases, Neuromuscular Diseases, Rheumatic Diseases
Conditions
Keywords
Pain, Sleep, Fibromyalgia, FM
Brief summary
The present trial is designed to assess the safety and efficacy of TNX-102 SL 2.8 mg tablets, taken daily at bedtime after 12 weeks of treatment in patients with fibromyalgia. The use of low-dose sublingual formulation of cyclobenzaprine (TNX-102 SL) dosed nightly for fibromyalgia is supported by the results of TNX-CY-F202 Phase 2b study -- the results provide strong evidence that TNX-102 SL 2.8 mg dosed nightly results in beneficial effects upon pain, sleep and other FM symptomatology.
Interventions
DRUGTNX-102 SL Tablet, 2.8 mg
Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.
Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 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 * Patients currently receiving pharmacologic treatment for depression should have been clinically stable for at least 3 months prior to randomization, and on stable doses of antidepressants during this 3 month time frame. * Willing and able to withdraw specific therapies (ask PI) * If female, medically acceptable form of contraception or not of child bearing potential. * Provide written informed consent to participate. * Willing and able to comply with all protocol specified requirement.
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\>45
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weekly Mean Pain Score | Day 1, Week 12 | The primary efficacy endpoint is the proportion of patients with a ≥30% improvement from baseline to Week 12 in the weekly average of the daily self-reported average pain severity score using an 11-point (0-10) numeric response scale (NRS). A score of 0 indicates no pain at all, and a score of 10 indicates worst possible pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fibromyalgia Impact Questionnaire (FIQR) Revised, Symptoms Domain | Day 1, Week 12 | Change from Baseline in the FIQR symptoms domain score at Week 12. The FIQ-R symptom domain is composed of 10 questions. All questions are based on an 11-point numerical rating scale (NRS) of 0-10, with 10 being worst. Symptom domain scores range from 0-100, with higher scores reflecting worse status. |
| Fibromyalgia Impact Questionnaire (FIQR) Revised, Functional Domain Score | Day 1, Week 12 | Change from Baseline in the FIQR function domain score at Week 12. The FIQ-R functional domain score is composed of 9 questions which are rated on an 11-point numerical rating scale (NRS) of 0-10, with 10 being worst. FIQ-R functional domain scores can range from 0-90, with higher scores reflecting worsening status. |
| Daily Diary Sleep | Week 12 | Change from Baseline in the weekly average of the daily diary assessment of sleep quality at Week 12. Daily sleep quality was measured using an 11-point (0-10) numerical rating scale (NRS), with higher scores representing worse sleep. |
| Patient's Global Impression of Change (PGIC) | Week 12 | Proportion of patients with a PGIC rating of very much improved or much improved at Week 12.The PGIC is a 7-point scale (1=very much improved; 7=very much worse) that assesses the patient's perception of the overall change in his/her fibromyalgia symptoms since entering the study. |
| Patient Reported Outcomes Measurement System (PROMIS), Fatigue | Week 12 | Change from Baseline in the PROMIS score for fatigue at Week 12. The Patient-Reported Outcome Measurement Information System (PROMIS) fatigue instrument consists of 8 items in which responses are scored 1 to 5 for each item. A higher score on 5 of the 8 items reflects a worse outcome, whereas a higher score on 3 items reflects an improved outcome; therefore, the directionality of the 8 item scores are first synchronized prior to calculation of the total raw score. PROMIS scores are presented as T-scores in which the raw score has been rescaled into a standardized score with a mean of 50 and a standard deviation of 10. Higher T-scores represent more of the concept being measured (in this case, sleep disturbance). |
| Daily Diary Pain | Week -1 (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. Average daily pain was measured using an 11-point (0-10) numerical rating scale (NRS), with higher scores representing worse pain. Weekly averages were calculated based on the reported daily scores. |
| 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 Patient-Reported Outcome Measurement Information System (PROMIS) sleep disturbance instrument consists of 8 items in which responses are scored 1 to 5 for each item. PROMIS scores are presented as T-scores in which the raw score has been rescaled into a standardized score with a mean of 50 and a standard deviation of 10. Higher T-scores represent more of the concept being measured (in this case, sleep disturbance). |
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 0 for 12 weeks. | 27 |
| TNX-102 SL Tablet, 2.8 mg 1 x TNX-102 SL 2.8 mg Tablet taken sublingually each day at bedtime for 12 weeks
TNX-102 SL Tablet, 2.8 mg: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks. | 24 |
| Total | 51 |
Baseline characteristics
| Characteristic | Placebo SL Tablet | Total | TNX-102 SL Tablet, 2.8 mg |
|---|---|---|---|
| Age, Continuous | 51.4 years STANDARD_DEVIATION 10.1 | 51.7 years STANDARD_DEVIATION 8.87 | 52.1 years STANDARD_DEVIATION 7.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 44 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) White | 19 Participants | 41 Participants | 22 Participants |
| Region of Enrollment United States | 27 participants | 51 participants | 24 participants |
| Sex: Female, Male Female | 24 Participants | 47 Participants | 23 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 24 |
| other Total, other adverse events | 0 / 27 | 0 / 24 |
| serious Total, serious adverse events | 0 / 27 | 0 / 24 |
Outcome results
Primary
Weekly Mean Pain Score
The primary efficacy endpoint is the proportion of patients with a ≥30% improvement from baseline to Week 12 in the weekly average of the daily self-reported average pain severity score using an 11-point (0-10) numeric response scale (NRS). A score of 0 indicates no pain at all, and a score of 10 indicates worst possible pain.
Time frame: Day 1, Week 12
Population: This study was stopped for business reasons prior to any patients completing the study. Therefore, no efficacy analyses were performed.
Secondary
Daily Diary Pain
Change from baseline to Week 12 in the weekly average of the daily self-reported average pain severity score. Average daily pain was measured using an 11-point (0-10) numerical rating scale (NRS), with higher scores representing worse pain. Weekly averages were calculated based on the reported daily scores.
Time frame: Week -1 (Day -7 to Day -1), Week 12
Population: This study was stopped for business reasons prior to any patients completing the study. Therefore, no efficacy analyses were performed.
Secondary
Daily Diary Sleep
Change from Baseline in the weekly average of the daily diary assessment of sleep quality at Week 12. Daily sleep quality was measured using an 11-point (0-10) numerical rating scale (NRS), with higher scores representing worse sleep.
Time frame: Week 12
Population: This study was stopped for business reasons prior to any patients completing the study. Therefore, no efficacy analyses were performed.
Secondary
Fibromyalgia Impact Questionnaire (FIQR) Revised, Functional Domain Score
Change from Baseline in the FIQR function domain score at Week 12. The FIQ-R functional domain score is composed of 9 questions which are rated on an 11-point numerical rating scale (NRS) of 0-10, with 10 being worst. FIQ-R functional domain scores can range from 0-90, with higher scores reflecting worsening status.
Time frame: Day 1, Week 12
Population: This study was stopped for business reasons prior to any patients completing the study. Therefore, no efficacy analyses were performed.
Secondary
Fibromyalgia Impact Questionnaire (FIQR) Revised, Symptoms Domain
Change from Baseline in the FIQR symptoms domain score at Week 12. The FIQ-R symptom domain is composed of 10 questions. All questions are based on an 11-point numerical rating scale (NRS) of 0-10, with 10 being worst. Symptom domain scores range from 0-100, with higher scores reflecting worse status.
Time frame: Day 1, Week 12
Population: This study was stopped for business reasons prior to any patients completing the study. Therefore, no efficacy analyses were performed.
Secondary
Patient Reported Outcomes Measurement System (PROMIS), Fatigue
Change from Baseline in the PROMIS score for fatigue at Week 12. The Patient-Reported Outcome Measurement Information System (PROMIS) fatigue instrument consists of 8 items in which responses are scored 1 to 5 for each item. A higher score on 5 of the 8 items reflects a worse outcome, whereas a higher score on 3 items reflects an improved outcome; therefore, the directionality of the 8 item scores are first synchronized prior to calculation of the total raw score. PROMIS scores are presented as T-scores in which the raw score has been rescaled into a standardized score with a mean of 50 and a standard deviation of 10. Higher T-scores represent more of the concept being measured (in this case, sleep disturbance).
Time frame: Week 12
Population: This study was stopped for business reasons prior to any patients completing the study. Therefore, no efficacy analyses were performed.
Secondary
Patient Reported Outcomes Measurement System (PROMIS), Sleep Disturbance
Change from Baseline in the PROMIS score for sleep disturbance at Week 12. The Patient-Reported Outcome Measurement Information System (PROMIS) sleep disturbance instrument consists of 8 items in which responses are scored 1 to 5 for each item. PROMIS scores are presented as T-scores in which the raw score has been rescaled into a standardized score with a mean of 50 and a standard deviation of 10. Higher T-scores represent more of the concept being measured (in this case, sleep disturbance).
Time frame: Day 1, Week 12
Population: This study was stopped for business reasons prior to any patients completing the study. Therefore, no efficacy analyses were performed.
Secondary
Patient's Global Impression of Change (PGIC)
Proportion of patients with a PGIC rating of very much improved or much improved at Week 12.The PGIC is a 7-point scale (1=very much improved; 7=very much worse) that assesses the patient's perception of the overall change in his/her fibromyalgia symptoms since entering the study.
Time frame: Week 12
Population: This study was stopped for business reasons prior to any patients completing the study. Therefore, no efficacy analyses were performed.