Safety and Tolerability of Esreboxetine in Fibromyalgia: Results from an Open-label, Flexible-dose, Phase 3 Extension Study

Currently, there are only three FDA-approved medications for the treatment of fibromyalgia. Real-world studies demonstrate that these medications are frequently discontinued within 6 to 12 months of initiation, often due to tolerability concerns. This leaves patients with limited treatment options for this debilitating condition. Esreboxetine is a novel, extended-release, potent and highly-selective norepinephrine reuptake inhibitor under investigation for the treatment of fibromyalgia in adults. Esreboxetine has demonstrated efficacy and safety in randomized, placebo-controlled trials for the treatment of fibromyalgia (Arnold, 2010; Arnold, 2012). Here we present the long-term safety of flexibly dosed esreboxetine (4-10 mg) in patients with fibromyalgia who enrolled in an open-label extension study after completing a 14-week, Phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trial (NCT00612170). A total of 386 participants (93% female) were included in the safety population. The median treatment duration was 101 days (range 1-297) and 64 participants were treated for over six months. A total of 287 (74.4%) participants reported adverse events (AEs) and 47 (12.2%) discontinued due to AEs (all causality). The most common AEs (>10%) were dry mouth (15.0%), constipation (14.2%), nausea (12.2%), and insomnia (10.9%). Most AEs were mild to moderate in severity and consistent with the pharmacology of esreboxetine. Only 6 participants (1.6%) discontinued due to insufficient clinical response. These data provide additional support for the overall safety, tolerability, and continued clinical development of esreboxetine for the treatment of fibromyalgia, a patient population with significant unmet medical need.