A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis.
Collin C,
Ehler E,
Waberzinek G,
Alsindi Z,
Davies P,
Powell K,
Notcutt W,
O'Leary C,
Ratcliffe S,
Nováková I,
Zapletalova O,
Piková J,
Ambler Z.
Source
Royal Berkshire and Battle Hospitals NHS Trust, London Road, Reading, Berkshire RG1 5AN, UK. christine.collin@royalberkshire.nhs.ukAbstract
BACKGROUND:
Muscle spasticity is common in multiple sclerosis (MS), occurring in more than 60% of patients.
OBJECTIVE:
To compare Sativex with placebo in relieving symptoms of spasticity due to MS.
METHODS:
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.
RESULTS:
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, p=0.035); and 36% versus 24% (responders, p=0.040). These were supported by the time to response (ITT: p=0.068; PP: p=0.025) analyses, carer global impression of change assessment (p=0.013) and timed 10-meter walk (p=0.042). 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.
DISCUSSION AND CONCLUSIONS:
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 responder/non-responder status.
