SIAXI

Abstract

Objective This pivotal phase III study, SIAXI, investigated the efficacy and safety of incobotulinumtoxinA for the treatment of chronic sialorrhea due to Parkinson disease (PD), atypical parkinsonism, stroke, or traumatic brain injury (TBI). Methods Adult patients with PD (70.7%), atypical parkinsonism (8.7%), stroke (19.0%), or TBI (2.7%) were randomized (2:2:1) to double-blind treatment with placebo (n = 36), or total doses of incobotulinumtoxinA 75 U (n = 74) or 100 U (n = 74), in a single treatment cycle. The coprimary endpoints were change in unstimulated salivary flow rate from baseline to week 4, and patients' Global Impression of Change Scale score at week 4. Adverse events were recorded throughout. Results A total of 184 patients were randomized. Both incobotulinumtoxinA dose groups showed reductions in mean unstimulated salivary flow rate at week 4, with a significant difference vs placebo in the incobotulinumtoxinA 100 U group ( p = 0.004). Patients' Global Impression of Change Scale scores also improved at week 4, with a significant difference vs placebo in the incobotulinumtoxinA 100 U group ( p = 0.002). A lasting effect was observed at week 16 post injection. The most frequent treatment-related adverse events in the incobotulinumtoxinA 75 U and 100 U groups were dry mouth (5.4% and 2.7% of patients) and dysphagia (2.7% and 0.0% of patients). Conclusions IncobotulinumtoxinA 100 U is an effective and well-tolerated treatment of chronic sialorrhea in adults. ClinicalTrials.gov identifier NCT02091739. Classification of evidence This study provides Class I evidence that incobotulinumtoxinA reduces salivary flow rates in patients with chronic sialorrhea due to PD, atypical parkinsonism, stroke, or TBI. AE= : adverse event; AESI= : adverse event of special interest; ALS= : amyotrophic lateral sclerosis; BoNT= : botulinum neurotoxin; DSFS= : Drooling Severity and Frequency Scale; GICS= : Global Impression of Change Scale; LS-means= : least squares means; MMRM= : mixed model repeated measurement; MP= : main period; mROMP= : modified Radboud Oral Motor Inventory for Parkinson's Disease; PD= : Parkinson disease; SIAXI= : Sialorrhea in Adults Xeomin Investigation; TBI= : traumatic brain injury; uSFR= : unstimulated salivary flow rate