The purpose of this study is to determine whether Sativex® versus Placebo is effective in the relief of symptoms of spasticity in subjects with multiple sclerosis, who have been identified as having a capacity to respond to Sativex.
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.
Official Title: A Two-phase, Phase 3 Study of the Safety and Efficacy of Sativex, in the Symptomatic Relief of Spasticity in Subjects With Spasticity Due to Multiple Sclerosis: Phase A - Single-blind Response Assessment; Phase B - Double-blind, Randomised, Placebo Controlled, Parallel Group Study.
Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.
containing ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring and colouring FD&C Yellow No.5 (E102 tartrazine) (0.0260%), FD&C Yellow No.6 (E110 sunset yellow) (0.0038%), FD&C Red No. 40 (E129 Allura red AC) (0.00330%) and FD&C Blue No.1 (E133 Brilliant blue FCF) (0.00058%).
Subjects were asked "On a scale of '0 to 10' please indicate the average level of your spasticity over the last 24 hours" with the anchors: 0 = 'no spasticity' and 10 = 'worst possible spasticity'. They were asked to relate 'no spasticity' to the time prior to the onset of their spasticity.
The subjects' baseline spasm frequency was the mean of the last seven days scores (Week 4) of Phase A treatment. The variable for analysis was the change in mean spasm frequency from baseline to the end of treatment (last 7 days of Week 17 Phase B).
The sleep disruption NRS score was recorded by subjects via a daily call to the interactive voice response system at bedtime. Subjects were asked "On a scale of '0 to 10' please indicate how you your spasticity disrupted your sleep last night" with the anchors: 0 = 'did not disrupt sleep' and 10 = 'completely disrupted (unable to sleep at all)'.
This was a 21-question multiple choice self-report inventory. Subjects' responses to the 21 questions were assigned a score ranging from zero to three, indicating the severity of the symptom. The sum of all BDI-II question scores indicated the severity of depression; score range 0-63. An decrease in score indicates an improvement in condition.
Diagnosed with any disease sub-type of MS of at least six months duration.
Spasticity due to MS of at least three months duration, which is not wholly relieved with current anti-spasticity therapy, and which is expected to remain stable for the duration of the study.
Subject fulfils at least one of the two criteria below. Subject must be either: Currently established on a regular dose of anti-spasticity therapy or Previously tried and failed, or could not tolerate suitable anti-spasticity therapy.
Subject is currently receiving a stable regimen (for at least 30 days prior to study entry) of all medications that may have an effect on spasticity; and willing to maintain this for the duration of the study. If the subject is currently taking disease-modifying medication, this must be at a stable dose for at least three months prior to the screening visit; the dose must also remain stable for the duration of the study.
Willing for his or her name to be notified to his or her primary care physician, and consultant and the responsible authorities for participation in this study, as applicable.
Any concomitant disease or disorder that has spasticity-like symptoms or that may influence the subject's level of spasticity.
Subject's medical history suggests that relapse/remission is likely to occur during the study (over the next 19 weeks) which, in the opinion of the investigator, is expected to influence the subject's spasticity.
Currently receiving a prohibited medication and unwilling to stop for the stated period prior to the screening visit and for the duration of the study.
Any known or suspected history of: schizophrenia or other psychotic illness;diagnosed dependence disorder;poorly controlled epilepsy or recurrent seizures;hypersensitivity to cannabinoids.
Significant cardiac, renal or hepatic disease.
Female subject who is pregnant, lactating or planning pregnancy during the course of the study or for three months thereafter.
Subjects who have received an IMP within the 12 weeks before Visit 1.
Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the result of the study, or the subject's ability to participate in the study.