P-046 - (Poster #46) Randomized, double-blind, placebo-controlled confirmatory Phase 3 trial of bedtime sublingual cyclobenzaprine (TNX-102 SL) in fibromyalgia

Background: Fibromyalgia (FM) is a nociplastic syndrome of chronic widespread pain, nonrestorative sleep, fatigue, cognitive dysfunction, and mood symptoms. RESILIENT was a confirmatory Phase 3 trial of daily bedtime TNX-102 SL (sublingual cyclobenzaprine [CBP] HCl) 5.6 mg in patients with FM.

Purpose/Objectives: To report the efficacy of TNX-102 SL in the treatment of FM from RESILIENT, a Phase 3, randomized, placebo-controlled trial.

Methods: Across 33 US sites, 457 patients meeting the 2016 Revised FM criteria were randomized 1:1 to 2 weeks of TNX-102 SL 2.8 mg followed by 12 weeks of TNX-102 SL 5.6 mg or to matching placebo (PBO). The primary endpoint was Week 14 change from baseline in weekly average of daily diary numeric rating scale (NRS) pain intensity. Six key secondary endpoints were Patient Global Impression of Change (PGIC) responders (ie, “much” or “very much” improved); Fibromyalgia Impact Questionnaire - Revised (FIQR) Symptoms (S) and Function (F) domains; PROMIS Sleep Disturbance (SD) and Fatigue; and sleep quality by daily diary NRS. The primary and continuous key secondary efficacy endpoints were analyzed by a mixed model for repeated measures with multiple imputation, and dichotomous endpoints were analyzed by Pearson chi-squared testing with multiplicity adjustment and type 1 error control by prespecified sequential testing waterfall. Exploratory secondary endpoints were the Beck Depression Inventory-II (BDI-II), and individual FIQR items. All patients received e-learning training on placebo response reduction and accurate pain reporting at every visit.

Results: TNX-102 SL significantly reduced FM pain at Week 14 (LS mean [SE] difference vs PBO of −0.7 [0.16]; P=0.00005; effect size=0.38). Significant improvements were also observed in PGIC (TNX-102 SL response 35.1% vs 19.1% PBO, P=0.0001); FIQR-S (P=0.000002); FIQR-F (P=0.001); PROMIS SD (P=0.0000001) and Fatigue (P=0.00009); and sleep quality (P=0.0007). Among exploratory endpoints, BDI-II total score (P=0.001, uncorrected) and the FIQR Memory item (P=0.001, uncorrected) were more improved with TNX-102 SL than PBO. The only systemic adverse events (AEs) at >3.0% incidence rate were COVID-19, headache, and somnolence. Administration site reactions of oral hypoesthesia were the most frequent (TNX-102 SL, 23.8%; PBO, 0.4%) and were transient, self-limited, and rated most often as mild (22.1%), occasionally as moderate (1.7%), and never as severe. Comparing TNX-102 SL-treated patients with and without oral sensory AEs showed no significant difference in the treatment effect on pain.

Conclusions/Implications for future research and/or clinical care: This confirmatory Phase 3 study demonstrates that TNX-102 SL significantly improved a broad spectrum of core FM symptoms, including widespread pain, nonrestorative sleep, fatigue, and global function. TNX-102 SL also improved depressive symptoms and cognitive function and had a favorable tolerability profile. These results suggest TNX-102 SL has potential to treat FM at a syndromal level.

Supported by: Tonix Pharmaceuticals.