BEdtime Sublingual TNX-102 SL as Fibromyalgia Intervention Therapy (BESTFIT)

Study Overview
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Brief Summary
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TNX-102 capsules [formerly known as very low dose (VLD) cyclobenzaprine] at bedtime have shown promise as a treatment of fibromyalgia, but the drug required new formulation technology for bedtime use. The present trial was 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.

Official Title
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A Phase 2b, Double-Blind, Randomized, Multicenter, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TNX-102 SL Tablets Taken at Bedtime in Patients With Fibromyalgia

Conditions
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Primary Fibromyalgia

Intervention / Treatment
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* Drug: TNX-102 SL 2.8mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of primary Fibromyalgia (ACR criteria) Male or female 18-65 years old For patients with major depressive disorders only: clinically stable, no suicidal risk and stable anti-depressent 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-off specific medications (ask PI) Known hypersensitivity to cyclobenzaprine Others: seizure disorders, sleep apnea, continuous positive airway pressure (CPAP) use, BMI>40

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TNX-102 SL 2.8 mg<br>Patients will take 1 tablet of TNX-102 SL sublingually each day at bedtime for 12 weeks. | Drug: TNX-102 SL 2.8mg<br>* Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.<br>* Other names: Low dose cyclobenzaprine sublingual tablets;|
| Placebo Comparator: Placebo<br>Patients will take 1 tablet of placebo sublingually each day at bedtime for 12 weeks. | Drug: Placebo<br>* Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.<br>* Other names: Placebo sublingual tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Weekly Average of Daily Pain Scores at Week 12 | Daily pain scores were assessed using a 24-hour recall response provided by each patient via an interactive voice response system (IVRS) daily telephone diary. Average daily pain was measured using an 11-point (0-10) numerical rating scale (NRS), with higher scores representing worse pain. Jump to control was used to replace missing data in each treatment arm. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30% Responder Analysis of IVRS NRS Pain Assessments at Week 12 | The weekly averages of daily pain scores were calculated using the daily, 24-hour-recall, IVRS NRS pain assessments. Patients who had at least a 30% improvement from baseline to week 12 in weekly average of daily pain scores were considered responders. | Baseline, Week 12 | 
| Change From Baseline to Week 12 in PROMIS T-score for Sleep Disturbance | 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. 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). | Baseline, Week 12 | 
| Patient Global Impression of Change (PGIC) Responder Status (Very Much Improved or Much Improved vs All Other Categories) 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. Scores of 1 and 2 were considered responders. | Week 12 | 
| Change From Baseline to Week 12 in FIQ-R Total Score | The Fibromyalgia Impact Questionnaire (revised) FIQ-R is made up of 3 domains: functional (9 questions), overall (2 questions) and symptoms (10 questions). All questions are based on an 11-point numerical rating scale (NRS) of 0-10, with 10 being worst. Total FIQ-R scores can range from 0-100, with higher scores reflecting worsening status. The patient's total score on the FIQ-R was assessed at Visits 2, 3, 4, 5, and 6 (Week 12). Jump to control was used to replace missing data in each treatment arm. | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, sleep