Siaxi: Efficacy and safety of incobotulinumtoxina for the treatment of sialorrhea in parkinson's disease (PD), stroke, and other neurological conditions: Results of a phase iii, placebo-controlled, randomized, double-blind study

Objective: To examine the safety and efficacy of incobotulinumtoxinA in the treatment of sialorrhea due to PD and other etiologies. Design: Prospective, randomized, double-blind, placebo-controlled, parallel-group study. Setting: 33 European sites. Participants: Adults with chronic, troublesome sialorrhea due to Parkinson's disease (PD), stroke, and other etiologies. Interventions: 75U or 100U incobotulinumtoxinA, or placebo. For the higher/lower dose groups, 15U/20U of incobotulinumtoxinA were injected into each submandibular gland, and 22.5U/30U into each parotid gland. Main Outcome Measures: Co-primary outcomes: Unstimulated Salivary Flow Rate (uSFR) at week 4 vs baseline and Global Impression of Change Scale (GICS) at week 4. Secondary outcomes: Drooling Severity and Fre-quency Scale (DSFS); modified Radboud Oral Motor Inventory in Parkinson's Disease (mROMP) drooling. Safety was monitored throughout. Results: 184 subjects received treatment (75U, n=74; 100U, n=74; placebo, n=36). Sialorrhea etiologies: PD (70.6%), atypical Parkinson syndromes (8.7%), stroke (17.9%), traumatic brain injury (2.7%). The 100U group showed-0.13 g/min (SE 0.026, 95% CI) LS-mean uSFR reduction and +1.25 points (SE 0.144, 95% CI) LS-mean improvement on GICS at week 4 compared with baseline. Both coprimary outcomes were significantly greater in the 100U dose group vs placebo at week 4 (P<.005). The 75U dose was numerically more effective than placebo at week 4 but did not reach statistical significance. Improvements in uSFR and GICS at weeks 8 and 12 were observed in both incobotulinumtoxinA groups, with improvement in the uSFR maintained at week 16. DSFS and mROMP drooling assessments supported the effectiveness of both doses. The safety and tolerability profile was favorable; no new or unexpected safety signals were identified. Conclusions: Doses of 75U and 100U incobotulinumtoxinA are effective up to 16 weeks for treatment of sialorrhea in PD and other neurological conditions; greater improvement was observed for the 100U treatment without meaningful added risks for adverse effects.