Background/Purpose: Fibromyalgia (FM) is characterized by chronic widespread pain and sleep disturbance.  Treatments that improve sleep quality in FM patients may improve fibromyalgia by a mechanism distinct from centrally acting analgesics.  TNX-102 SL¹is a proprietary eutectic sublingual (SL) tablet formulation of low-dose cyclobenzaprine HCl (2.8 mg) designed for rapid absorption and long-term bedtime use.  This double-blind, randomized, placebo-controlled multicenter study (BESTFIT) evaluated the safety and efficacy of TNX-102 SL in FM.

Methods: A total of 205 patients who met ACR 2010 FM criteria were enrolled at 17 sites in a 12-week, double-blind, placebo-controlled trial. Patients were randomized 1:1 to receive TNX-102 SL (N=103) or placebo (N=102).   Outcome measures included daily pain and sleep diaries (0-10 NRS averaged over each week), Fibromyalgia Impact Questionnaire (FIQ-R), Patient Global Impression of Change (PGIC), and PROMIS Sleep Disturbance scale (PROMIS).  Data were analyzed by mean change from baseline using Mixed Effects Model Repeated Measures (MMRM) unless otherwise noted.

Results: Patients treated with TNX-102 SL showed improvement in multiple domains of FM.  Responder analysis of week 12 daily diary pain (with =>30% improvement from baseline defined as response) was statistically significant with a 34.0% pain response rate compared to 20.6% for placebo; p = 0.033.  This same pain diary data showed a decrease in pain by -1.5 compared to -1.0 for placebo; p = 0.086. Pain scores reported during clinic visits (7 day recall NRS) showed significant improvement (p = 0.033) as did the pain item on the FIQ-R (7 day recall), p = 0.004.  

TNX-102 SL improved the FIQ-R total score by -15.6 compared to -8.5 for placebo, p = 0.014. PGIC response rate(responses of 1 or 2 on a 7 point Likert Scale) was improved vs. placebo (30.1% vs. 16.7%, p = 0.025 by logistic regression).  All measures of sleep quality improved, including PROMIS sleep disturbance with an -9.0 improvement on TNX-102 SL compared to -5.1 on placebo, p = 0.005.  Sleep as measured by daily diary (change from baseline) was improved by -1.9 compared to -0.9 on placebo; p = <0.001, and the sleep quality item on the FIQ-R improved by -2.9 compared to -1.1 on placebo; p <0.001. 

Systemic adverse events (AEs) were infrequent, no item was reported in >5% of TNX-102 SL- treated patients and were similar to the placebo-treated patients.  Local administration site reactions (transient tongue or sublingual numbness) were commonly reported, occurring in approximately 42% of treated patients.  Only 3 patients withdrew from participation in the study due to local adverse events. 86% of TNX-102 SL treated patients completed versus 83% on placebo.

Conclusion: Bedtime TNX-102 SL improved sleep quality by several measures and also improved multiple other symptoms and domains of FM.  Nonrestorative sleep has been linked to central sensitization, which is characterized by changes in central pain processing.  Together these findings suggest that sleep quality is a target of therapy in FM and TNX-102 SL improvement in sleep quality was well tolerated was associated with broad symptomatic improvement.

¹TNX-102 SL is an Investigational New Drug and has not been approved for any indication.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/bedtime-rapidly-absorbed-sublingual-cyclobenzaprine-tnx-102-sl-for-the-treatment-of-fibromyalgia-results-of-a-phase-2b-randomized-double-blind-placebo-controlled-study/