"RIV/00843989:_____/11:00101893" . "Gasperini, C." . "Erdmann, A." . "Stelmasiak, Z." . "European journal of neurology" . "1351-5101" . . . "randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex\u00AE), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis" . . "Zapletalov\u00E1, Olga" . . "GB - Spojen\u00E9 kr\u00E1lovstv\u00ED Velk\u00E9 Brit\u00E1nie a Severn\u00EDho Irska" . . . "Rossi, P." . . "Montalban, X." . . "n. 9" . "Ratcliffe, S." . "1"^^ . "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."@en . "000294347200012" . "[8026C62EA82E]" . "10"^^ . "Pozzilli, C." . . . "17"^^ . . . "RIV/00843989:_____/11:00101893!RIV14-MZ0-00843989" . "randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex\u00AE), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis"@en . "Davies, P." . . . "10.1111/j.1468-1331.2010.03328.x" . . "randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex\u00AE), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis" . "Klimek, A." . . . . . . . . "Nov\u00E1kov\u00E1, I." . "cannabidiol; cannabinoids; delta-9-tetrahydrocannabinol; endocannabinoid system; multiple sclerosis; nabiximols; Sativex; spasticity"@en . "Ambler, Z." . "randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex\u00AE), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis"@en . "Cefaro, L." . "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." . "18" . "Mare\u0161, J." . "184099" . "V\u00E1chov\u00E1, M." . "N, S, V" . "Comi, G." . "Novotn\u00E1, A." .