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
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
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DOI：
10.1111/j.1468-1331.2010.03328.x
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发表时间：
2011-09-01
影响因子：
5.1
通讯作者：
Davies, P.
中科院分区：
文献类型：
--
作者：
Novotna, A.;Mares, J.;Davies, P.
背景：痉挛是多发性硬化症的一种致残性并发症，影响许多患者的病情。我们报告的第一个3期安慰剂对照研究的口服解痉剂使用一个丰富的study design.Methods：一个为期19周的随访，多中心，双盲，随机，安慰剂对照，平行组研究的主题与多发性硬化症痉挛没有完全缓解，目前的解痉治疗。受试者与nabiximols治疗，作为添加治疗，在一个单盲的方式为4周，之后，那些实现了改善痉挛>= 20%进展到一个12周的随机，安慰剂对照phase.Results：在572名受试者登记，272个实现了>= 20%的改善后，4周的单盲治疗，241随机。主要终点是在随机对照研究阶段，治疗组之间平均痉挛数字评定量表（NRS）的差异。意向性治疗（ITT）分析显示了非常显著的差异，有利于那比昔莫（P = 0.0002）。反应者分析的次要终点、痉挛频率评分、睡眠障碍NRS患者、护理人员和临床医生的总体印象变化均显着有利于纳比西莫。结论：丰富的研究设计提供了一种以更接近地反映所提出的临床实践的方式确定那比西莫的功效和安全性的方法，通过限制暴露于可能从中受益的那些患者。活性药物和安慰剂之间的差异应反映预期治疗人群的疗效和安全性。
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.