SIAXI: IncobotulinumtoxinA for sialorrhea in Parkinson’s disease, stroke, and other etiologies-Phase 3 Results (S30.007)

Objective: To examine the safety and efficacy of incobotulinumtoxinA for treating sialorrhea due to PD and other etiologies.

Background: Sialorrhea is troublesome and disabling symptom often associated with various neurological conditions.

Design/Methods: The study enrolled adults with chronic, troublesome sialorrhea due to neurological etiologies (eg, PD, stroke). Subjects were randomized to 3 groups: 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. Study duration was 16±2 weeks post-injection. Co-primary outcomes: Unstimulated Salivary Flow Rate (uSFR) at week 4 vs baseline and Global Impression of Change Scale (GICS) at week 4 post-injection. Secondary assessments: Drooling Severity and Frequency Scale (DSFS) and modified Radboud Oral Motor Inventory in Parkinson’s Disease (mROMP)-drooling. Adverse events were monitored throughout.

Results: 184 subjects were randomized to 3 treatment groups: 75U (n=74), 100U (n=74), or placebo (n=36). Sialorrhea etiologies: PD (70.6%), stroke (17.9%), atypical Parkinson syndromes (8.7%), traumatic brain injury (2.7%). At week 4, the LS-mean uSFR reduction for the 100U group was −0.13 g/min (SE 0.026, 95%CI); the LS-mean GICS improvement was +1.25 points (SE 0.144, 95%CI) at week 4. Both co-primary outcomes were significantly greater in the 100U dose group vs placebo at week 4 (P<0.005). Although the 75U dose was numerically more effective than placebo, it did not reach statistical significance. Maintenance of improvements in uSFR and GICS was observed for both doses through week 16. DSFS and mROMP drooling assessments supported the effectiveness of both doses. No new or unexpected safety signals were observed; safety and tolerability were favorable.

Conclusions: IncobotulinumtoxinA is effective for treating of sialorrhea in PD and other neurological conditions through 16 weeks. A greater improvement was observed at the 100U dose without meaningful increased safety risks.

Study Supported by: Study sponsored by Merz Pharmaceuticals GmbH.

Disclosure: 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. Dr. Friedman has received research support from Merz. Dr. Michel has received research support from Merz. Dr. Flatau-Baqué has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz. Dr. Csikós has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz. Dr. Jost has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan plc, Ipsen, and Merz.