Once-nightly sublingual cyclobenzaprine 5.6 mg dose reduced fibromyalgia pain more than placebo at week 14, according to a recent study.
The researchers reported that the treatment was associated with clinically meaningful reductions in pain and improvements in sleep and fatigue among patients with fibromyalgia. The phase 3 randomized, double-blind, multicenter, placebo-controlled trial enrolled 457 adults at 33 US sites and evaluated once-nightly sublingual cyclobenzaprine titrated from 2.8 mg dose for 2 weeks to 5.6 mg dose for 12 weeks versus placebo over 14 weeks following screening, washout, and a 7-day baseline run-in.
The modified intent-to-treat population included 456 patients. The primary endpoint was change from baseline at week 14 in the weekly average of daily diary pain intensity measured on an 11-point numeric rating scale (NRS). Secondary endpoints included the Patient Global Impression of Change, the Fibromyalgia Impact Questionnaire, Revised (FIQR) Symptoms and Function domains, Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance and Fatigue, and diary sleep quality. Efficacy was assessed with a mixed model for repeated measures using multiple imputation; a prespecified sequential testing strategy-controlled type I error.
Completion rates were 81.0% with patients who received sublingual cyclobenzaprine (187 of 231) and 79.6% with patients who received the placebo (179 of 225). “The LS mean change from baseline at week 14 in the weekly average of the daily mean NRS pain intensity scores was significantly greater with TNX-102 SL vs placebo (−1.8 vs −1.2, respectively; LS mean difference [LSMD] vs placebo [95% CI], −0.7 [−1.0 to −0.3]; effect size, 0.38; P < .001),” noted Seth Lederman, MD, of Tonix Pharmaceuticals, Inc., Chatham, New Jersey, and colleagues. All six secondary endpoints favored active therapy: Patient Global Impression of Change responders increased by 16.0%; FIQR Symptoms improved by a least-squares mean difference of −7.7 and FIQR Function by −5.4; PROMIS Sleep Disturbance decreased by −4.2 and PROMIS Fatigue by −3.0; diary sleep quality improved by −0.6. Exploratory analyses showed by week 14, 45.9% of patients that received higher proportions of sublingual cyclobenzaprine had at least 30% less pain compared with 27.1% on placebo, and 22.5% of patients had at least 50% less pain compared with 13.3% on placebo.
Treatment-emergent adverse events (TEAEs) led to discontinuation in 6.1% of patients with active treatment and 3.5% of patients with placebo. Overall TEAEs occurred in 58.9% of patients versus 36.7% of patients and were mostly mild or moderate. With active treatment, oral administration-site events were common and transient, including oral numbness (23.8%), altered taste (11.7%), and tingling (6.9%).
Serious TEAEs were uncommon (0.9% of patients versus 1.3% receiving placebo); no deaths occurred.
Full disclosures can be found in the published study.
Source: Pain Medicine