Long-term Efficacy and Safety of IncobotulinumtoxinA Treatment for Sialorrhea (S4.007)

Objective: To assess the long-term efficacy and safety of incobotulinumtoxinA 75U and 100U in subjects with sialorrhea. Background: SIAXI (NCT02091739), was a randomized, double-blind, placebo-controlled, 16-week Phase III study with a 48-week extension period (EP). Here we present data from the complete study. Design/Methods: In the main period (MP), subjects with sialorrhea due to Parkinson’s disease, atypical Parkinsonism, stroke, or traumatic brain injury were randomized (2:2:1) to incobotulinumtoxinA 75U, 100U (n=74 each), or placebo (n=36) in a single injection cycle (IC). Eligible subjects entered the EP and received three incobotulinumtoxinA 75U or 100U ICs (16±2 week duration). Outcomes included: unstimulated salivary flow rate (uSFR), and scores on the subjects’ Global Impression of Change Scale (GICS), Drooling Severity and Frequency Scale (DSFS), modified Radboud Oral Motor Inventory for Parkinson’s disease (mROMP) (Kalf JG et al. Arch Phys Med Rehabil 2011; 92: 1152–1158) and EuroQoL 5-dimensions visual analog scale (EQ-5D VAS). Adverse events (AEs) were reported. Results: In total, 173/184 subjects completed the MP and entered the EP. In all ICs, uSFR decreased from study baseline with repeated ICs in incobotulinumtoxinA 75U- or 100U-treated subjects (mean [standard deviation] change from study baseline to end-of-study −0.16 [0.21] and −0.17 [0.23] g/min, respectively). Subjects’ GICS improved at all visits and DSFS, mROMP drooling scores, and EQ-5D VAS improved from study baseline to 4 weeks post-injection in each IC. mROMP speech and swallowing symptom scores remained stable. The most common treatment-related AEs for incobotulinumtoxinA 75U and 100U, respectively, were dry mouth (4.4% and 11.1%) and dysphagia (1.5% and 4.2%). Two subjects reported serious treatment-related AEs including speech disorder (one incobotulinumtoxinA 75U recipient) and dysphagia (one incobotulinumtoxinA 100U recipient). Conclusions: These data support the long-term efficacy and safety of repeated incobotulinumtoxinA treatment for sialorrhea. Disclosure: Dr. Pagan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz, US WorldMeds, Acadia, Teva, AbbVie, Sunovion, and Acorda. Dr. Pagan has received research support from US WorldMeds and Medtronic. Dr. Jost has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan, Ipsen, and Merz. Dr. Oehlwein has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Medtronic. Dr. Slawek has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Allergan, Merz, Ipsen, and Roche. Dr. Slawek has received personal compensation in an editorial capacity for Polish Neurological Society. Dr. Bogucki has nothing to disclose. Dr. Ochudlo has nothing to disclose. Dr. Banach has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz. Dr. Banach has received research support from Merz, Ipsen, Kedrion, Shire, Allergan. Dr. Csikos has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz Pharmaceuticals GmbH. Dr. Blitzer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz. Dr. Blitzer has received research support from Merz.