Efficacy and safety of incobotulinumtoxinA for the treatment of sialorrhea: Results of the main phase of a phase 3 study

Introduction: Intractable sialorrhea results from various causes, including Parkinson's disease (PD). The pivotal, double-blind, randomized, Phase 3 SIAXI study (NCT02091739) assessed the efficacy and safety of incobotulinumtoxinA (botulinum neurotoxin type A [BoNT-A] free from complexing proteins) 75 U and 100 U for the treatment of sialorrhea. Methods: Adults included in the main phase (MP) had chronic, troublesome sialorrhea due to PD, atypical Parkinsonism, stroke, or traumatic brain injury (TBI) and were randomized (2:2:1) to a single injection cycle (16±2 weeks) of incobotulinumtoxinA 75 U or 100 U, or placebo (PBO) distributed in bilateral parotid and submandibular glands (dose ratio of 3:2). Co-primary endpoints were change in unstimulated salivary flow rate (uSFR) and subjects' Global Impression of Change Scale (GICS) at Week 4. Safety was also assessed. Results: One hundred eighty-four subjects were randomized to either incobotulinumtoxinA 75 U (n=74), 100 U (n=74), or PBO (n=36) in the MP. Primary drooling etiologies were: PD (70.7%), atypical Parkinsonism (8.7%), stroke (17.9%), and TBI (2.7%). Injection was guided by anatomic landmarks in 39.2%, 44.6%, and 50.0%, and ultrasonography in 60.8%, 55.4%, and 50.0% of subjects in the incobotulinumtoxinA 75 U, 100 U, and PBO groups, respectively. At week 4, incobotulinumtoxinA 100 U significantly improved uSFR, and subjects' GICS scores were significantly higher vs PBO (both, P