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

Authors


  • See editorial by Claudio Solaro, on page 1113.

  • Sativex does not yet have an INN, but the product does have a US Adopted Name (USAN): ‘nabiximols’. Therefore, we use ‘nabiximols’ in preference to the full product name throughout the text.

  • Trial registration: The details of this study were registered on clinicaltrials.gov (Ref. NCT00681538).

MU Dr. A. Novotna, Krajska nemocnice Pardubice, Neurologicke odd., Kyjevska 44, 632 03 Pardubice, Czech Republic (tel.: +420 467 434701; fax: +420 466 014702; e-mail: novotna-alena@quick.cz).

Abstract

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 4 weeks, 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 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 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.

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