Following concomitant administration with levodopa/carbidopa CR 200 mg/50 mg, single doses of nebicapone 50 mg, 100 mg and 200 mg significantly and dose-dependently inhibited S-COMT activity, increased systemic exposure to levodopa, and reduced 3-OMD formation.
Objective: An assessment of clinically important change is useful in interpreting clinical trial outcomes. The 4-point Ashworth Scale (AS) is a widely accepted measure of muscle tone, and the 9-point Physician Global Assessment Score (PGAS) is a global measure of post-treatment change as evaluated by the physician. The quantitative relationship between AS and PGAS has not previously been described in spasticity.
Methods:Data from three clinical trials of botulinum toxin type A (BOTOX; Allergan, Irvine, CA) in poststroke spasticity were analyzed (n ϭ 442). Mean change from baseline in AS score was plotted as a function of PGAS and correlations were calculated. Receiver-operator curve (ROC) analyses with the wrist flexor AS change from baseline as the independent variable and PGAS as the dependent variable were performed using the following criteria: PGAS of Ն1 (mild improvement or better) and PGAS of Ն2 (moderate improvement or better).Results: In pooled data, the Pearson's correlation coefficient r between the change in wrist Ashworth Score and the PGAS was Ϫ0.44 (p ϭ 0, t ϭ Ϫ26.5). Pearson correlations by individual study were also statistically significant. By ROC analysis, a PGAS of Ն1 was associated with 33% reduction of wrist AS and a PGAS of Ն2 was associated with approximately 50% reduction. In a well-powered phase 3 study, the Pearson's correlation coefficient was even higher (r ϭ Ϫ0.76, p ϭ 0, t ϭ Ϫ28.5).Conclusions: Changes in disease-specific scales that correlate significantly with changes in physician global assessments are considered clinically meaningful. In clinical trials of chronic spasticity, we found that 33% and 50% changes in the Ashworth Scale scores correlate with 1-point or 2-point changes in PGAS. This is similar to findings from pooled chronic pain studies, in which 30% and 50% changes on the pain numeric rating scale were considered clinically important (Farrar et al., Pain 2001;94:149 -158).
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