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.The primary endpoint of the study was painscores as measured on a patient diary card using an 11-point NRS (range0 10).A summary of the results is given below, and the primary endpoint pre-sented in Figure 5.Forty-eight patients were enrolled.They all had at least one brachial plexusroot avulsion for at least 18 months.They also had pain of at least 4 on an11-point NRS at the time of enrolment.The study was a randomized, dou-ble-blind, crossover design consisting of three 2-week periods following arun-in period of 7 24 days.Patients continued on all previous stable medica-tions including analgesics.During each 2-week period subjects received, inrandom order, either placebo, formulated Tetranabinex® or Sativex®.Thesewere given as patient-activated oromucosal 100 µl sprays.Efficacy endpoints were: 11 point NRSs for pain and sleep, short-formMcGill (McGill Pain Questionnaire), General Health Questionnaire-12(GHQ-12) and sleep quality and sleep disturbance were all recorded.The mean number of daily sprays taken in the final week of treatment was6.93 for Sativex®(range 1.1 22.2, SD 4.79), 7.26 for Tetranabinex® (range1.2 21.6, SD 5.04) and 9.15 for placebo (range 2.0 35.6, SD 7.30).Theresults for the efficacy endpoints are shown in Table 2.252 G.W.Guy and C.G.StottTable 2.Study GWBP0101 efficacy resultsFormulatedBaseline Placebo Tetranabinex® Sativex®Pain NRS Score 6.7 6.7 6.1 (P = 0.002) 6.1 (P = 0.005)McGill Pain Questionnaire(total intensity) 17.3 15.5 13.4 (P = 0.04) 13.8 (P = 0.15)McGill (Part II)Pain-intensity VAS score 60.9 52.9 43.6 (P = 0.04) 45.1 (P = 0.09)Sleep-quality NRS 4.8 5.2 6.0 (P = 0.001) 5.9 (P = 0.02)GHQ-12 13.4 13.5 12.3 (P = 0.18) 10.9 (P = 0.02)VAS, Visual Analogue Scale; GHQ-12, General Health Questionnaire-12.These two studies [55, 56] and a third reported by Sharief [57] demonstratethat Sativex® has a significant analgesic effect in CNP.A further study yet tobe fully reported also demonstrated a significant improvement in peripheralneuropathic pain characterized by allodynia [60].These results are consistentwith a recent report of dronabinol being effective in CNP in MS [61].Symptoms of MSIn addition to reports of Sativex® being effective in the treatment of neuropath-ic pain, early studies indicated that it had a broad spectrum of activity across avariety of other symptoms in MS such as spasm, spasticity and bladder dys-function [51 53].In order to test the breadth of effect of the medicine, a studywas undertaken evaluating a range of nominated primary symptoms in MS [58].Patients chose one of five symptoms (pain, spasm spasticity, tremor or blad-der dysfunction) as their nominated primary symptom.Despite their existingtreatment prior to study entry, patients were required to have a symptom sever-ity rated as >50 mm on a 100-mm VAS scale in order to be eligible.Other sec-ondary impairments/symptoms (if present) were also monitored during thestudy.A total of 160 patients entered a baseline period (14 days maximum); fol-lowed by a 6-week randomized, double-blind, placebo-controlledparallel-group comparison of Sativex® with placebo.Patients self-titrated tosymptom resolution or maximum tolerated dose.Existing medication contin-ued at a constant dose.Primary efficacy comparisons were made between symptom scores record-ed during baseline and scores recorded at the end of the 6-week parallel groupperiod.Patients then entered weeks 7 10 and all patients were re-titrated on toSativex® and received open-label treatment for 4 weeks.The development of Sativex®  a natural cannabis-based medicine 253The results of the study are presented below and the outcome on the symp-tom of spasticity is presented in Figures 6 and 7.Thirty-nine patients (n = 19 for Sativex®, n = 18 for the placebo) who nom-inated spasticity as their primary impairment showed a statistically significantimprovement in their spasticity VAS scores as assessed at either their clinicvisits or as recorded on their daily diary cards.When the changes in each of the clinic visit spasticity VAS scores (inpatients with spasticity as a primary impairment) were analysed, there was ahighly statistically significant treatment difference of 22.79 mm in spasticityin favour of Sativex® (P = 0.001).When the changes in each of the diary card spasticity VAS scores (inpatients with spasticity as a primary impairment) were analysed, there was ahighly statistically significant treatment difference of 18.41 mm in spasticityin favour of Sativex® (P = 0.009).Effect on sleepThe most consistent endpoint in terms of response to Sativex® (measured in allGW studies except GWMS0106) has been the improvement in sleep quali-ty/sleep disturbance reported by patients which chronic symptoms, irrespec-tive of the aetiology.Patients with chronic refractory pain of neurological ori-gin, CNP (from conditions such as MS and brachial plexus avulsion), periph-eral neuropathic pain, and other symptoms of MS such as spasm, spasticityand bladder dysfunction have all reported statistically significant improve-ments in sleep (Fig.8).It is well accepted that sleep quality has a major impact on the quality of lifeof patients with chronic conditions.In the above clinical studies, Sativex® hasnot only produced statistically and clinically significant improvements in thepatients primary symptoms, but also the ability to gain rest as a result of therelief of those symptoms.On average across the studies Sativex® has produceda 40% improvement in sleep quality/disturbance.However, the effect of Sativex® on sleep is not due to a direct hypnoticeffect of the medicine.The effect of Sativex® on the sleep process was inves-tigated in a sleep laboratory study [62].Nicholson et al.have reported the effects of Sativex® and formulatedTetranabinex® on nocturnal sleep and early-morning behaviour in young adults[62].The effects of the medicines on nocturnal sleep, early-morning perform-ance, memory and sleepiness were studied in eight healthy volunteers.The study was double-blind and placebo-controlled with a four-waycrossover design [ Pobierz caÅ‚ość w formacie PDF ]