This 19 week, multicentre study was conducted in two phases. Phase A was a preliminary, single-blind four week treatment period to identify subjects with a capacity to respond to Sativex; eligible, consenting subjects entered a seven day screening period prior to returning to the study centre to begin a four week single-blind course of Sativex treatment. At the end of this phase, subjects\' response to Sativex was assessed; those with the capacity to respond (i.e. at least a 20% reduction in mean 0-10 point numerical rating scale (NRS) spasticity score between screening and the end of the four week Phase A treatment) were eligible for entry into Phase B while those who did not respond took no further part in the study other than a follow up visit 14 days later.
Phase B was a 12 week double-blind, randomised, placebo controlled, parallel group study with visits at 28 day intervals and a final follow up visit 14 days after completion or withdrawal.
The level of spasticity, spasm frequency and sleep disruption were collected each day during the entire study via an interactive voice response system (IVRS). In addition, study medication dosing data were recorded via IVRS throughout Phases A and B. Assessments of other secondary and functional measures of spasticity, safety and tolerability, QOL (quality of life) and mood were also gathered throughout the study.
ANTECEDENTES: La espasticidad es una complicación incapacitante de la esclerosis múltiple, que afecta a muchos pacientes con la condición. Se presenta el estudio controlado con placebo de fase 3 primero de un agente antiespástico oral a utilizar un diseño de estudio enriquecido.
MÉTODOS: A 19 semanas de seguimiento, multicéntrico, doble ciego, aleatorizado, controlado con placebo, de grupos paralelos en pacientes con esclerosis múltiple espasticidad no está completamente aliviado con la terapia antiespástico actual. Los sujetos fueron tratados con Sativex, como terapia añadida, de una manera simple ciego de 4 semanas, después de lo cual los consecución de una mejora en la espasticidad de ≥20% progresaron a un niño de 12 semanas, aleatorizado, controlado con placebo de fase.
RESULTADOS: De los 572 sujetos reclutados, 272 lograron una mejoría ≥20% después de 4 semanas de tratamiento simple ciego, y 241 fueron asignados al azar. El punto final primario fue la diferencia entre los tratamientos en la espasticidad media numérico Rating Scale (NRS) en la fase aleatorizada y controlada del estudio. La intención de tratar (ITT) el análisis mostró una diferencia altamente significativa a favor del Sativex (P = 0,0002). Secundaria puntos finales de análisis de respuesta, espasmo Frecuencia Score, Trastornos del sueño NRS paciente, cuidador y Clínico Global Impression of Change estaban significativa a favor del Sativex.
CONCLUSIONES: El diseño del estudio enriquecido proporciona un método de determinar la eficacia y seguridad de Sativex de una manera que refleja más estrechamente propuso la práctica clínica, mediante la limitación de la exposición a aquellos pacientes que son propensos a beneficiarse de ella. Por lo tanto, la diferencia entre activo y placebo debe ser un reflejo de la eficacia y la seguridad en la población destinada al tratamiento.
BACKGROUND: Sativex® (THC.:CBD oromucosal spray) is indicated as add-on treatment for patients with moderate to severe multiple sclerosis (MS) spasticity. We aimed to determine whether antispasticity treatment history influenced the efficacy and safety of add-on THC.:CBD oromucosal spray in MS spasticity patients.
METHODS: Post hoc analysis of an enriched-design clinical trial of THC.:CBD oromucosal spray versus placebo, using records of patients under previous and current ineffective antispasticity therapies. Subgroups were patients with at least 1 failed therapy attempt with either baclofen or tizanidine (Group 1) or at least 2 failed therapy attempts with both baclofen and tizanidine (Group 2).
SUMMARY: Of 241 patients in the intent-to-treat population, 162 and 57 patients met the criteria for Groups 1 and 2, respectively. In all groups, response on the spasticity 0-10 Numerical Rating Scale was significantly greater with THC.:CBD oromucosal spray versus placebo, for minimal clinically important difference (MCID ≥18% improvement vs. baseline) and clinically important difference (CID, ≥30% improvement vs. baseline). THC.:CBD oromucosal spray improved spasticity-related symptoms such as sleep quality and timed 10-meter walk independent of the number of prior failed therapy attempts. Tolerability was not influenced by pre-treatment history.
CONCLUSIONS: THC.:CBD oromucosal spray provided consistent relief with good tolerability in MS spasticity patients irrespective of their antispasticity pre-treatment history.
This 19 week, multicentre study was conducted in two phases. Phase A was a preliminary, single-blind four week treatment period to identify subjects with a capacity to respond to Sativex; eligible, consenting subjects entered a seven day screening period prior to returning to the study centre to begin a four week single-blind course of Sativex treatment. At the end of this phase, subjects\' response to Sativex was assessed; those with the capacity to respond (i.e. at least a 20% reduction in mean 0-10 point numerical rating scale (NRS) spasticity score between screening and the end of the four week Phase A treatment) were eligible for entry into Phase B while those who did not respond took no further part in the study other than a follow up visit 14 days later.
Phase B was a 12 week double-blind, randomised, placebo controlled, parallel group study with visits at 28 day intervals and a final follow up visit 14 days after completion or withdrawal.
The level of spasticity, spasm frequency and sleep disruption were collected each day during the entire study via an interactive voice response system (IVRS). In addition, study medication dosing data were recorded via IVRS throughout Phases A and B. Assessments of other secondary and functional measures of spasticity, safety and tolerability, QOL (quality of life) and mood were also gathered throughout the study.
País»United Kingdom
Diseño del estudio»Ensayo controlado aleatorizado (ECA)
