Fibromyalgia
Conditions
Keywords
Pain, Sleep, Fibromyalgia, FM
Brief summary
This is a Phase 3, randomized, parallel-group, double-blind, placebo-controlled, 14-week study designed to evaluate the efficacy and safety of TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) taken daily at bedtime for the treatment of fibromyalgia.
Interventions
DRUGTNX-102 SL
Patients will take 1 tablet of randomly assigned study drug sublingually starting on Day 1 for 2 weeks. At the Week 2 visit, all patients will have the dose increased to 2 tablets for 12 weeks.
Patients will take 1 tablet of randomly assigned study drug sublingually starting on Day 1 for 2 weeks. At the Week 2 visit, all patients will have the dose increased to 2 tablets 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 65 Years
Healthy volunteers
No
Inclusion criteria
* The patient is male or female 18 to 65 years of age, inclusive. * The patient has a diagnosis of primary FM as defined by the 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria (American College of Rheumatology Preliminary Diagnostic Criteria) * The in-clinic 7-day recall NRS average daily pain intensity score at Screening Visit within protocol specified range.
Exclusion criteria
* History of or evidence for a diagnosis of borderline personality disorder (BPD).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 14 in the Numerical Rating Scale (NRS) Weekly Average of Daily Self-reported Average Pain Severity Scores. | 14 weeks | Patients provide a daily numeric assessment of their average pain (24-hour recall), via an electronic diary, using an 11-point NRS. Scores range from 0 (no pain) to 10 (worst possible pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 14 in the Fibromyalgia Impact Questionnaire - Revised (FIQR) Symptoms Domain Score | 14 weeks | The FIQ-R 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 14 in the FIQR Function Domain Score | 14 weeks | The FIQ-R is a validated questionnaire. Scores on the function domain range from 0 to 90 where a higher score means worse outcome. |
| Number of Patients With a Patient's Global Impression of Change (PGIC) Rating of Very Much Improved or Much Improved | 14 weeks | 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 a much worse outcome. |
| Change From Baseline to Week 14 in the PROMIS Score for Fatigue | 14 weeks | 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. |
| Change From Baseline to Week 14 in the Weekly Average of the Daily Diary Assessment of Sleep Quality | 14 weeks | 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). |
| Change From Baseline to Week 14 in the Patient Reported Outcomes Measurement Information System (PROMIS) Score for Sleep Disturbance | 14 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TNX-102 SL Tablets, 5.6 mg 1 x TNX-102 SL 2.8 mg Tablet taken sublingually each day at bedtime for 2 weeks then 2 x TNX-102 SL 2.8 mg (5.6 mg) Tablet taken sublingually each day at bedtime for 12 weeks.
TNX-102 SL: Patients will take 1 tablet of randomly assigned study drug sublingually starting on Day 1 for 2 weeks. At the Week 2 visit, all patients will have the dose increased to 2 tablets for 12 weeks. | 248 |
| Placebo SL Tablet 1 x Placebo Tablet taken sublingually each day at bedtime for 2 weeks then 2 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 starting on Day 1 for 2 weeks. At the Week 2 visit, all patients will have the dose increased to 2 tablets for 12 weeks. | 255 |
| Total | 503 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 21 | 9 |
| Overall Study | COVID-19 related crisis | 3 | 3 |
| Overall Study | Family emergency | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 8 |
| Overall Study | Lost to Follow-up | 4 | 9 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Subject non-compliance | 1 | 1 |
| Overall Study | Withdrawal by Subject | 12 | 11 |
Baseline characteristics
| Characteristic | TNX-102 SL Tablets, 5.6 mg | Total | Placebo SL Tablet |
|---|---|---|---|
| Age, Continuous | 50.0 years STANDARD_DEVIATION 9.4 | 49.6 years STANDARD_DEVIATION 9.79 | 49.3 years STANDARD_DEVIATION 10.16 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 39 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 12 Participants | 9 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 | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 222 Participants | 438 Participants | 216 Participants |
| Region of Enrollment United States | 248 participants | 503 participants | 255 participants |
| Sex: Female, Male Female | 232 Participants | 479 Participants | 247 Participants |
| Sex: Female, Male Male | 16 Participants | 24 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 248 | 0 / 255 |
| other Total, other adverse events | 70 / 248 | 3 / 255 |
| serious Total, serious adverse events | 2 / 248 | 5 / 255 |
Outcome results
Primary
Change From Baseline to Week 14 in the Numerical Rating Scale (NRS) Weekly Average of Daily Self-reported Average Pain Severity Scores.
Patients provide a daily numeric assessment of their average pain (24-hour recall), via an electronic diary, using an 11-point NRS. Scores range from 0 (no pain) to 10 (worst possible pain).
Time frame: 14 weeks
Population: Intent to Treat Population (all patient who were randomized). Multiple imputation for missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TNX-102 SL Tablets, 5.6 mg | Change From Baseline to Week 14 in the Numerical Rating Scale (NRS) Weekly Average of Daily Self-reported Average Pain Severity Scores. | -1.9 score on a scale |
| Placebo SL Tablet | Change From Baseline to Week 14 in the Numerical Rating Scale (NRS) Weekly Average of Daily Self-reported Average Pain Severity Scores. | -1.5 score on a scale |
p-value: 0.0195% CI: [-0.7, -0.1]Mixed Model Repeated Measures
Secondary
Change From Baseline to Week 14 in the Fibromyalgia Impact Questionnaire - Revised (FIQR) Symptoms Domain Score
The FIQ-R is a validated questionnaire. Scores on the symptoms domain range from 0 to 100 where a higher score means worse outcome.
Time frame: 14 weeks
Population: Intent to Treat Population (all patients who were randomized). Multiple imputation for missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TNX-102 SL Tablets, 5.6 mg | Change From Baseline to Week 14 in the Fibromyalgia Impact Questionnaire - Revised (FIQR) Symptoms Domain Score | -18.4 score on a scale |
| Placebo SL Tablet | Change From Baseline to Week 14 in the Fibromyalgia Impact Questionnaire - Revised (FIQR) Symptoms Domain Score | -14.0 score on a scale |
p-value: 0.00795% CI: [-7.5, -1.2]Mixed Model Repeated Measures
Secondary
Change From Baseline to Week 14 in the FIQR Function Domain Score
The FIQ-R is a validated questionnaire. Scores on the function domain range from 0 to 90 where a higher score means worse outcome.
Time frame: 14 weeks
Population: Intent to Treat Population (all patients who were randomized). Multiple imputation for missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TNX-102 SL Tablets, 5.6 mg | Change From Baseline to Week 14 in the FIQR Function Domain Score | -13.6 score on a scale |
| Placebo SL Tablet | Change From Baseline to Week 14 in the FIQR Function Domain Score | -9.3 score on a scale |
p-value: 0.00995% CI: [-7.7, -1.1]Mixed Model Repeated Measures
Secondary
Change From Baseline to Week 14 in the Patient Reported Outcomes Measurement Information System (PROMIS) Score for Sleep Disturbance
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.
Time frame: 14 weeks
Population: Intent to Treat population (all patients who were randomized). Multiple imputation for missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TNX-102 SL Tablets, 5.6 mg | Change From Baseline to Week 14 in the Patient Reported Outcomes Measurement Information System (PROMIS) Score for Sleep Disturbance | -9.5 score on a scale |
| Placebo SL Tablet | Change From Baseline to Week 14 in the Patient Reported Outcomes Measurement Information System (PROMIS) Score for Sleep Disturbance | -6.5 score on a scale |
p-value: <0.00195% CI: [-4.5, -1.3]Mixed Model Repeated Measures
Secondary
Change From Baseline to Week 14 in the PROMIS Score for Fatigue
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.
Time frame: 14 weeks
Population: Intent to Treat population (all patients who were randomized). Multiple imputation for missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TNX-102 SL Tablets, 5.6 mg | Change From Baseline to Week 14 in the PROMIS Score for Fatigue | -8.0 score on a scale |
| Placebo SL Tablet | Change From Baseline to Week 14 in the PROMIS Score for Fatigue | -6.2 score on a scale |
p-value: 0.01895% CI: [-3.3, -0.3]Mixed Model Repeated Measures
Secondary
Change From Baseline to Week 14 in the Weekly Average of the Daily Diary Assessment of Sleep Quality
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: 14 weeks
Population: Intent to Treat population (all patients who were randomized). Multiple imputation for missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TNX-102 SL Tablets, 5.6 mg | Change From Baseline to Week 14 in the Weekly Average of the Daily Diary Assessment of Sleep Quality | -2.0 score on a scale |
| Placebo SL Tablet | Change From Baseline to Week 14 in the Weekly Average of the Daily Diary Assessment of Sleep Quality | -1.5 score on a scale |
p-value: <0.00195% CI: [-0.9, -0.3]Mixed Model Repeated Measures
Secondary
Number of Patients With a Patient's Global Impression of Change (PGIC) Rating of Very Much Improved or Much Improved
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 a much worse outcome.
Time frame: 14 weeks
Population: Intent to Treat population (all patient who were randomized). Patients with missing data as non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TNX-102 SL Tablets, 5.6 mg | Number of Patients With a Patient's Global Impression of Change (PGIC) Rating of Very Much Improved or Much Improved | 93 Participants |
| Placebo SL Tablet | Number of Patients With a Patient's Global Impression of Change (PGIC) Rating of Very Much Improved or Much Improved | 75 Participants |
p-value: 0.05895% CI: [0.99, 2.1]Regression, Logistic