Primary Fibromyalgia
Conditions
Keywords
TNX-102 SL, bedtime, sublingual, 12-month, long term safety, long term efficacy, Fibromyalgia
Brief summary
This was an open-label, extension trial designed to evaluate the long-term safety over 12 months of TNX-102 SL tablets taken daily at bedtime for the treatment of fibromyalgia. Patients recruited into this trial were those who had successfully completed the double-blind study, TNX-CY-F202 (F202) (NCT01903265). Patients were not made aware of the therapy they received during the double-blind study.
Detailed description
The study consisted of 7 clinic visits, including Screening/Baseline Visit 1 (Day 0 which was typically the same date as Visit 6 of the double-blind lead-in study), visits after 1, 3, 6, 9, and 12 months of treatment (Visits 2-6), and a Follow-up Visit (Visit 7) scheduled within one month after stopping study drug treatment. Primary: The primary objective of the study was to evaluate the long-term safety of TNX-102 SL tablets taken daily at bedtime over 12 months in patients with fibromyalgia who have completed Study TNX-CY-F202 (NCT01903265) Secondary: The secondary objective was to evaluate the long-term efficacy of TNX-102 SL tablets taken daily at bedtime to control symptoms of fibromyalgia
Interventions
DRUGTNX-102 SL
TNX-102 SL 2.8 mg taken daily at bedtime.
Sponsors
Tonix Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. The patient met all prior inclusion and exclusion requirements for Study F202 (NCT01903265) originally, and has had no intervening medical conditions, increased suicidal ideation, or requirements for concomitant medications that preclude exposure to TNX-102 SL or enrollment in the extension study. 2. The patient completed expected dosing in F202 (NCT01903265) defined as taking study medication up to Week 12, with at least 70% compliance with medication usage (based on responses from daily IVRS calls recorded during the F202 study (NCT01903265)) and no major protocol violations. 3. The patient has provided written informed consent to participate in this extension protocol.
Exclusion criteria
None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Newly-emergent Adverse Events (NEAEs) During Treatment With TNX-102 SL Tablets Taken Daily at Bedtime Over 12 Months in Patients With Fibromyalgia. | Up to 12 months | NEAEs and Serious Adverse events (SAEs) were collected and are coded using the latest version of the Medical Dictionary for Regulatory Activities (MedDRA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Months 1, 3, 6, 9 and 12. | The NRS for average pain was an 11-point scale (0=no pain → 10=worst pain imaginable) that was assessed on a 24-hour recall basis. |
| Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Month 1, 3, 6, 9, 12 | The NRS for average pain over the past 7 days was an 11-point scale (0=no pain → 10=worst pain imaginable) that was assessed on a 7-day recall basis. |
| Responder Analysis of Patient's Global Impression of Change (PGIC) | Months 1, 3, 6, 9, 12 | PGIC is a fibromyalgia-specific validated instrument to gauge the patient's assessment of change in condition.The scores are categorized as provided below. A responder was defined by a score of 1 (very much improved), or 2 (much improved). 1. = Very much improved 2. = Much improved 3. = Minimally improved 4. = No change 5. = Minimally worse 6. = Much worse 7. = Very much worse |
Countries
United States
Participant flow
Recruitment details
One hundred fifty-eight (158) of the 174 patients who completed 12 weeks of treatment in Study F202 were eligible and consented to participate in the 12-month safety extension study.
Pre-assignment details
Restricted to patients who completed the lead-in double-blind study and continued to meet the inclusion/exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Placebo - TNX-102 SL 2.8 mg 1x TNX-102 SL 2.8 mg sublingual tablet taken daily at bedtime for 12 months
TNX-102 SL: TNX-102 2.8 mg SL taken daily at bedtime. | 79 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg 1x TNX-102 SL 2.8 mg sublingual tablet taken daily at bedtime for 12 months
TNX-102 SL: TNX-102 2.8 mg SL taken daily at bedtime. | 79 |
| Total | 158 |
Baseline characteristics
| Characteristic | Placebo - TNX-102 SL 2.8 mg | TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 0 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 75 Participants | 79 Participants | 154 Participants |
| Age, Continuous | 50.2 Years | 51.7 Years | 50.9 Years |
| Sex: Female, Male Female | 78 Participants | 75 Participants | 153 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 79 | 0 / 79 |
| other Total, other adverse events | 43 / 79 | 39 / 79 |
| serious Total, serious adverse events | 3 / 79 | 5 / 79 |
Outcome results
Primary
Newly-emergent Adverse Events (NEAEs) During Treatment With TNX-102 SL Tablets Taken Daily at Bedtime Over 12 Months in Patients With Fibromyalgia.
NEAEs and Serious Adverse events (SAEs) were collected and are coded using the latest version of the Medical Dictionary for Regulatory Activities (MedDRA).
Time frame: Up to 12 months
Population: All of the 158 enrolled patients took at least 1 dose of study drug and were included in the safety analysis population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo - TNX-102 SL 2.8 mg | Newly-emergent Adverse Events (NEAEs) During Treatment With TNX-102 SL Tablets Taken Daily at Bedtime Over 12 Months in Patients With Fibromyalgia. | Patient with at least 1 NEAE reported | 60 Participants |
| Placebo - TNX-102 SL 2.8 mg | Newly-emergent Adverse Events (NEAEs) During Treatment With TNX-102 SL Tablets Taken Daily at Bedtime Over 12 Months in Patients With Fibromyalgia. | Patients withdrew due to NEAE | 18 Participants |
| Placebo - TNX-102 SL 2.8 mg | Newly-emergent Adverse Events (NEAEs) During Treatment With TNX-102 SL Tablets Taken Daily at Bedtime Over 12 Months in Patients With Fibromyalgia. | Patient with at least 1 SAE | 3 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Newly-emergent Adverse Events (NEAEs) During Treatment With TNX-102 SL Tablets Taken Daily at Bedtime Over 12 Months in Patients With Fibromyalgia. | Patient with at least 1 NEAE reported | 54 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Newly-emergent Adverse Events (NEAEs) During Treatment With TNX-102 SL Tablets Taken Daily at Bedtime Over 12 Months in Patients With Fibromyalgia. | Patient with at least 1 SAE | 5 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Newly-emergent Adverse Events (NEAEs) During Treatment With TNX-102 SL Tablets Taken Daily at Bedtime Over 12 Months in Patients With Fibromyalgia. | Patients withdrew due to NEAE | 9 Participants |
Secondary
Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall
The NRS for average pain was an 11-point scale (0=no pain → 10=worst pain imaginable) that was assessed on a 24-hour recall basis.
Time frame: Months 1, 3, 6, 9 and 12.
Population: Patients who took at least 1 dose of study drug prior to study discontinuation were included in the efficacy analysis. By the end of the study, 36 patients from the Placebo - TNX-102 SL group and 25 patients from the TNX-102 SL - TNX-102 SL group had discontinued the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Baseline | 5.6 Scores on a scale | Standard Deviation 2.29 |
| Placebo - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Change at Month 1 | -0.5 Scores on a scale | Standard Deviation 1.96 |
| Placebo - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Change at Month 3 | -0.5 Scores on a scale | Standard Deviation 1.86 |
| Placebo - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Change at Month 6 | -0.7 Scores on a scale | Standard Deviation 2.18 |
| Placebo - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Change at Month 9 | -0.6 Scores on a scale | Standard Deviation 2.36 |
| Placebo - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Change at Month 12 | 0.1 Scores on a scale | Standard Deviation 2.08 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Change at Month 9 | 0.0 Scores on a scale | Standard Deviation 1.91 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Baseline | 5.0 Scores on a scale | Standard Deviation 2.52 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Change at Month 6 | -0.2 Scores on a scale | Standard Deviation 2.32 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Change at Month 1 | -0.2 Scores on a scale | Standard Deviation 1.75 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Change at Month 12 | -0.0 Scores on a scale | Standard Deviation 2.26 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on 24 Hour Recall | Change at Month 3 | -0.3 Scores on a scale | Standard Deviation 1.92 |
Secondary
Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall
The NRS for average pain over the past 7 days was an 11-point scale (0=no pain → 10=worst pain imaginable) that was assessed on a 7-day recall basis.
Time frame: Month 1, 3, 6, 9, 12
Population: Patients who took at least 1 dose of study drug prior to study discontinuation were included in the efficacy analysis. By the end of the study, 36 patients from the Placebo - TNX-102 SL group and 25 patients from the TNX-102 SL - TNX-102 SL group had discontinued the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Change at Month 12 | 0.0 Scores on a scale | Standard Deviation 1.72 |
| Placebo - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Change at Month 3 | -0.6 Scores on a scale | Standard Deviation 1.67 |
| Placebo - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Baseline | 5.7 Scores on a scale | Standard Deviation 2.09 |
| Placebo - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Change at Month 9 | -0.4 Scores on a scale | Standard Deviation 2.33 |
| Placebo - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Change at Month 6 | -0.7 Scores on a scale | Standard Deviation 2.06 |
| Placebo - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Change at Month 1 | -0.8 Scores on a scale | Standard Deviation 1.68 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Change at Month 12 | 0.2 Scores on a scale | Standard Deviation 1.84 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Baseline | 4.8 Scores on a scale | Standard Deviation 2.18 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Change at Month 1 | 0.1 Scores on a scale | Standard Deviation 1.13 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Change at Month 6 | 0.2 Scores on a scale | Standard Deviation 2.11 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Change at Month 9 | 0.0 Scores on a scale | Standard Deviation 2.07 |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Change From Baseline in Numerical Rating Scale (NRS) Assessments of Average Pain Based on a 7 Day Recall | Change at Month 3 | 0.1 Scores on a scale | Standard Deviation 1.85 |
Secondary
Responder Analysis of Patient's Global Impression of Change (PGIC)
PGIC is a fibromyalgia-specific validated instrument to gauge the patient's assessment of change in condition.The scores are categorized as provided below. A responder was defined by a score of 1 (very much improved), or 2 (much improved). 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: Months 1, 3, 6, 9, 12
Population: Patients who took at least 1 dose of study drug prior to study discontinuation were included in the efficacy analysis. Overall, 36 patients from the Placebo - TNX-102 SL group and 25 patients from the TNX-102 SL - TNX-102 SL group had discontinued the study early. Any missing PGIC responses were included in the scores 3-7 for that visit.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 1 | Score 1 or 2 | 16 Participants |
| Placebo - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 1 | Scores 3 to 7 | 63 Participants |
| Placebo - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 3 | Score 1 or 2 | 23 Participants |
| Placebo - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 3 | Scores 3 to 7 | 56 Participants |
| Placebo - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 6 | Score 1 or 2 | 22 Participants |
| Placebo - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 6 | Scores 3 to 7 | 57 Participants |
| Placebo - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 9 | Score 1 or 2 | 21 Participants |
| Placebo - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 9 | Scores 3 to 7 | 58 Participants |
| Placebo - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 12 | Score 1 or 2 | 17 Participants |
| Placebo - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 12 | Scores 3 to 7 | 62 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 9 | Scores 3 to 7 | 52 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 1 | Score 1 or 2 | 25 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 6 | Scores 3 to 7 | 53 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 1 | Scores 3 to 7 | 54 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 12 | Scores 3 to 7 | 47 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 3 | Score 1 or 2 | 29 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 9 | Score 1 or 2 | 27 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 3 | Scores 3 to 7 | 50 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 12 | Score 1 or 2 | 32 Participants |
| TNX-102 SL 2.8 mg - TNX-102 SL 2.8 mg | Responder Analysis of Patient's Global Impression of Change (PGIC) | Month 6 | Score 1 or 2 | 26 Participants |