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.

• Conditions: Spasticity in multiple sclerosis (MS)

• Registration Number: EUCTR2006-005910-11-DE
• Lead Sponsor: GW Pharma Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-02-08
• Last Update Posted: 31 July 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 488

Inclusion Criteria

Inclusion Criteria: Screening (i.e. at Visit 1)
The single blind status of Phase A must be maintained (i.e. subject should not be made aware of which IMP they are receiving). These criteria must be reviewed at all three visits prior to randomisation. Subjects meeting the following criteria will be considered eligible for this study:
· Willing and able to give written informed consent for participation in the study.
· Male or female, aged 18 years or above.
· Subject is able (in the investigator’s opinion) and willing to comply with all study requirements.
· 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.
· The subject has at least moderate spasticity (as defined by a score of =4 using a single spasticity severity NRS) at Visit 1.
· 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.
· In the investigator’s opinion, the subject is unaware of which IMP s/he will receive in Phase A.
· 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.

At Entry into Phase A – Single blind (i.e. Visit 2)
In order to remain eligible, the single blind status of Phase A must be maintained (i.e. subject should not be made aware of which IMP they will receive).
In order to continue in Phase A of the study, ALL subjects must meet the following additional criteria:
· Subjects have registered spasticity NRS scores via the IVRS over the six days (A2 to A7) from Visit 1. Subjects who are non-compliant will be deemed ineligible to continue.
· Subject has at least moderate spasticity at Visit 2: NRS spasticity scores, as recorded by the subject on all screening days (A2 to A7), sum to at least 24 (e.g. a score of 4 x 6 days).
· Subject has had a stable regimen (throughout Phase A) of all medications that may have an effect on spasticity or MS, and remains willing to maintain this for the duration of the study.
· In the investigator’s opinion, the subject is unaware of which IMP s/he will receive in Phase A.

At Entry into Phase B/Randomisation (i.e. Visit 3) – Double Blind
In order to remain eligible, the single blind status of Phase A must be maintained (i.e. subject should not be made aware of which IMP they have received) and subjects must not be informed that they may be changing IMP.
In order to proceed to randomisation, ALL subjects must meet the following additional criteria:
· The subject must have had at least a 20% reduction (comparing Weeks 1 and 5) in weekly mean NRS spasticity score, as recorded via IVRS, (i.e. defined as having the capacity to respond to treatment with Sativex).
· Subject has had a sta

Exclusion Criteria

Exclusion Criteria:
The subject may not enter/continue in the study if ANY of the following apply at any study visit prior to randomisation:
· 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 subjects of child bearing potential and male subjects whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective contraception during the study and for three months thereafter.
· 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.
· Following a physical examination, the subject has any abnormalities that, in the opinion of the investigator, would prevent them from safely participating in the study.
· Unwilling to abstain from donation of blood during the study.
· Travel outside the country of residence planned during the study.
· Subjects previously randomised into this study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of GW-1000-02 (named Sativex® in Canada and also named Sativex Oromucosal Spray) compared with placebo in relieving symptoms of spasticity due to multiple sclerosis (MS), in subjects identified as having a capacity to respond to Sativex.;Secondary Objective: To evaluate the effect of Sativex compared with placebo on:<br>· Secondary measures of spasticity.<br>· Functional measures of spasticity.<br><br>To assess the safety and tolerability of Sativex.;Primary end point(s): The primary endpoint is the mean spasticity NRS score over the last seven days of the evaluable period (end of treatment - usually week 17) in those subjects who demonstrated a response in Phase A.