SIAXI: Placebo-controlled, randomized, double-blind study of incobotulinumtoxinA for sialorrhea

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.

Clinicaltrialsgov 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.

Figure 1. Disposition of patients for the MP of the study

An AE leading to discontinuation occurring in one placebo patient was not considered a treatment-emergent AE (AE with onset or worsening at or after treatment). ^aMultiple reasons for withdrawal could be listed; ^bAEs were not treatment-related. AE = adverse event; MP = main period.

Figure 2. Clinical outcomes over time

(A) Change in uSFR from baseline to weeks 4, 8, 12, and 16; (B) patients' GICS score at weeks 1, 2, 4, 8, 12, and 16; and (C) change in DSFS sum score from baseline to weeks 4, 8, 12, and 16 post treatment. *p < 0.05, **p < 0.01, ***p ≤ 0.001, mixed model repeated measurement analysis based on change from baseline vs placebo in panels A and C, and the rating at each posttreatment assessment vs placebo in panel B. Reduction in uSFR and DSFS indicates improvement. GICS score: −3 (very much worse), −2 (much worse), −1 (minimally worse), 0 (no change in function), +1 (minimally improved), +2 (much improved) to +3 (very much improved). DSFS = Drooling Severity and Frequency Scale; GICS = Global Impression of Change Scale; LS-mean = least squares mean; SE = standard error; uSFR = unstimulated salivary flow rate.