• A Novotna, J Mares, S Ratcliffe, I Novakova, M Vachova, O Zapletalova, C Gasperini, C Pozzilli, L Cefaro, G Comi, P Rossi, Z Ambler, Z Stelmasiak, A Erdmann, X Montalban, A Klimek, P Davies, and Sativex Spasticity Study Group.
• Krajska nemocnice Pardubice, Neurologicke odd, Paradubice, Czech Republic. novotna-alena@quick.cz
• Eur. J. Neurol. 2011 Sep 1;18(9):1122-31.

Background  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.Methods  A 19-week follow-up, multicentre, double-blind, randomized, placebo-controlled, parallel-group study in subjects with multiple sclerosis spasticity not fully relieved with current antispasticity therapy. Subjects were treated with nabiximols, as add-on therapy, in a single-blind manner for 4weeks, after which those achieving an improvement in spasticity of ≥20% progressed to a 12-week randomized, placebo-controlled phase.Results  Of the 572 subjects enrolled, 272 achieved a ≥20% improvement after 4weeks 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 analysis, Spasm Frequency Score, Sleep Disturbance NRS Patient, Carer and Clinician Global Impression of Change were all significant in favour of nabiximols.Conclusions  The enriched study design provides a method of determining the efficacy and safety of nabiximols 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.© 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

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