A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis.
Muscle spasticity is common in multiple sclerosis (MS), occurring in more than 60% of patients. To compare Sativex with placebo in relieving symptoms of spasticity due to MS. A 15-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group study in 337 subjects with MS spasticity not fully relieved with current anti-spasticity therapy. The primary endpoint was a spasticity 0-10 numeric rating scale (NRS). Intention-to-treat (ITT) analysis showed a non-significant improvement in NRS score, in favor of Sativex. The per protocol (PP) population (79% of subjects) change in NRS score and responder analyses (> or 30% improvement from baseline) were both significantly superior for Sativex, compared with placebo -1.3 versus -0.8 points (change from baseline, p0.035) and 36% versus 24% (responders, p0.040). These were supported by the time to response (ITT p0.068 PP p0.025) analyses, carer global impression of change assessment (p0.013) and timed 10-meter walk (p0.042). Among the subjects who achieved a > or 30% response in spasticity with Sativex, 98, 94 and 73% reported improvements of 10, 20 and 30%, respectively, at least once during the first 4 weeks of treatment. Sativex was generally well tolerated, with most adverse events reported being mild-to-moderate in severity. The 0-10 NRS and responder PP analyses demonstrated that Sativex treatment resulted in a significant reduction in treatment-resistant spasticity, in subjects with advanced MS and severe spasticity. The response observed within the first 4 weeks of treatment appears to be a useful aid to prediction of respondernon-responder status.