Background Novel responder definitions for fibromyalgia (FM) clinical trials have been proposed by the Outcome Measures in Rheumatology (OMERACT) FM subcommittee. These definitions include key symptom and functional domains relevant to FM patients, and were validated using outcome data from 12 previous registration trials of 4 other medications (Arnold L et al, Arth Rheum 64:885, 2012.) TNX-102 SL* is a proprietary sublingual formulation of cyclobenzaprine designed for rapid absorption and bedtime use. It showed improvements in pain and other symptoms in a Phase 2B study. This study was a 12-week, randomized, double-blind, placebo-controlled trial conducted at 17 US sites, designed to evaluate TNX as a potential treatment for FM. 205 participants were randomized (TNX=103; placebo=102).
Objectives This current presentation is a retrospective analysis of the trial results using the two preferred response definitions proposed by the OMERACT committee.
Methods The two OMERACT responder definitions are: the FM30 Short, which defines a responder as ≥30% reduction in pain, ≥10% improvement in physical function plus a ≥30% improvement in either sleep or fatigue, and the FM30 Long, which defines a responder as ≥30% reduction in pain, ≥10% improvement in physical function plus ≥30% improvement in any two of the following measures: sleep, fatigue, depression, anxiety or cognition.
Results TNX improved multiple domains of FM. The table below compares a pain responder analysis (≥30% improvement in pain based on daily diary) to the alternative composite responder definitions proposed by OMERACT.
Additional improvements noted over placebo included: FIQ-R total score (-17.2 vs. -9.1, p=0.015),PGIC response rate (30.1% vs. 16.7%, p=0.025), PROMIS sleep (-9.5 vs -6.1, p=0.004), sleep based on daily diary (change from baseline to week-12, 1.9 vs. -1.0; p<0.001) and FIQ-R sleep item (-2.9 vs. -1.2; p<0.0001). Systemic adverse events reported were similar to placebo. The most common local adverse event was transient tongue or mouth numbness occurring in 44% of TNX patients.
Conclusions Bedtime TNX improved multiple domains of FM. Analysis by composite responder criteria developed by OMERACT suggests that the improvements in FM symptoms seen with TNX are not limited to an analgesic response, since these composite criteria all require improvement in other somatic and functional symptoms.
*TNX-102 SL is an Investigational New Drug and has not been approved for any indication.
Acknowledgement Supported by Tonix Pharmaceuticals, Inc.
Disclosure of Interest None declared