A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols, as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis

Research Subject: Multiple Sclerosis
Author: A. Novotna, J. Mares, S. Ratcliffe et al.
Publish Date: 2011

Spasticity is a disabling complication of multiple sclerosis, affecting many patients with the condition. We report the first Phase 3 placebo-controlled study of an oral antispasticity agent to use an enriched study design.

A 19-week follow-up, multicentre, double-blind, randomized, placebocontrolled, parallel-group study in subjects with multipie sclerosis spasticity not fully relieved with current antispasticity therapy, Subjects were treated with nabiximols, as add-on therapy, in a single-blind manner for 4 weeks, after which those achieving an improvement in spasticity of ;;::20% progressed to a 12-week randomized, placebo controlled phase.

Of the 572 subjects enrolled, 272 achieved a ;0:20% improvement after 4 weeks of single-blind treatment, and 241 were randomized. The primary end-point was the difference between treatments in the mean spasticity Numeric Rating Scale (NRS) in the randomized, controlled phase of the study. Intention-to-treat (ITT) analysis showed a highly significant difference in favour of nabiximols (P ~ 0.0002). Secondary end-points of responder anaiysis, Spasm Frequency Score, Sieep Disturbance NRS Patient, Carer and Clinician Giobal Impression of Change were all significant in favour of nabiximols.

The enriched study design provides a method of determining the efficacy and safety of nabiximois in a way that more closely reflects proposed clinical practice, by limiting exposure to those patients who are likely to benefit from it. Hence, the difference between active and placebo should be a reflection of efficacy and safety in the population intended for treatment.

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