| Summary: | In this first, double-blind, randomized, placebo-controlled exploratory trial, we evaluate the efficacy and safety of incobotulinumtoxinA and feasibility of using kinematic tremor assessment to aid in the planning of muscle selection in a multicenter setting. Reproducibility of the planning technology to other clinical sites was explored. In this trial (NCT02207946), patients with upper-limb essential tremor (ET) were randomized 2:1 to a single treatment cycle of incobotulinumtoxinA or placebo. A tremor kinematic analytics investigational device was used to define a customized muscle set for injection, related to the pattern of the wrist, forearm, elbow, and shoulder tremor for each patient, and the incobotulinumtoxinA dose per muscle (total ≤ 200 U). Fahn–Tolosa–Marin (FTM) Part B motor performance score, Global Impression of Change Scale (GICS), and kinematic analysis-based efficacy evaluations were assessed. Thirty patients were randomized (incobotulinumtoxinA, <i>n</i> = 19; placebo, <i>n</i> = 11). FTM motor performance scores showed greater improvement with incobotulinumtoxinA versus placebo at Week 4 (<i>p</i><i>=</i> 0.003) and Week 8 (<i>p</i><i>=</i> 0.031). The physician-rated GICS score indicated improvement with incobotulinumtoxinA versus placebo at Week 4 (<i>p</i> < 0.05). IncobotulinumtoxinA also decreased accelerometric hand-tremor amplitude versus placebo from baseline to Week 4 (<i>p</i><i>=</i> 0.004) and Week 8 (<i>p</i> < 0.001), with persistent tremor reduction up to 24 weeks post-injection. IncobotulinumtoxinA produced a slight and transient reduction of maximal grip strength versus placebo; two patients reported localized finger muscle weakness. Customized incobotulinumtoxinA injections decreased tremor severity and improved hand motor function in patients with upper-limb ET after a single injection cycle, with a favorable tolerability profile. The study showed that tremor kinematic analytics technology could be successfully scaled for use in other clinical sites.
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