THU0325 TNX-102 SL for the Treatment of Fibromyalgia: Role of Nonrestorative Sleep on Pain Centralization

BackgroundThe importance of nonrestorative sleep in the pathophysiology of fibromyalgia (FM) suggests that treatments that improve sleep quality may improve FM globally by a mechanism distinct from that of centrally acting analgesics. TNX-102 SL is a sublingual formulation of cyclobenzaprine (2.8 mg) designed for rapid absorption and bedtime use. The current study was designed to evaluate the safety and efficacy of TNX-102 SL in the treatment of FM.ObjectivesThe BESTFIT study was designed to evaluate whether the sleep quality improvement associated with TNX-102 SL treatment would lead to improvement in the pain and other symptoms of FM.MethodsBESTFIT was a 12-week, randomized, double-blind, placebo-controlled trial conducted at 17 investigational US sites. Under a US Investigational New Drug Application, 205 participants were randomized 1:1 to receive TNX-102 SL (N=103) or matching placebo (N=102). Outcome measures included daily diary assessment of pain and sleep (0-10 NRS), the Fibromyalgia Impact Questionnaire (FIQ-R), Patient Global Impression of Change (PGIC), PROMIS Sleep Disturbance scale (PROMIS), and mood (Beck Depression Inventory, BDI). Data were analyzed by mean change from baseline using Mixed Effects Model Repeated Measures (MMRM) unless otherwise noted.ResultsTNX-102 SL treatment improved multiple domains of FM. Treatment improved the FIQ-R total score by -17.2 compared to -9.1 for placebo, p=0.015. PGIC response rate was improved vs. placebo (30.1% vs. 16.7%, p=0.025 by logistic regression). Several measures of sleep quality improved, including the PROMIS with a -9.5 improvement on active compared to -6.1 on placebo, p=0.004. Sleep as measured by daily diary (change from baseline to endpoint) was improved by -1.9 compared to -1.0 on placebo; p