Clinical trial NCT00681538: A Study of the Safety and Effectiveness of Sativex®, for the Relief of Symptoms of Spasticity in Subjects, From Phase B, With Multiple Sclerosis (MS)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spasticity
Multiple Sclerosis
Keywords: Spasticity
Multiple Sclerosis
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-05-21
Enrollment: 572
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.
* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: The Change in Mean Spasticity Numerical Rating Scale (NRS) Score From Baseline to End of Treatment (Phase B).
timeFrame: Baseline (last 7 days of Week 4) - End of treatment (last 7 days of Week 17)
Secondary outcomes:
measure: Number of Subjects Showing an Improvement of at Least 30% or 50% in Their Mean NRS Spasticity Score (Phase B) From Baseline.
timeFrame: Baseline (Day 1) - End of treatment (last 7 days of Week 17)
measure: Change in Spasm Frequency (Number of Spasms Per Day) From Baseline to End of Treatment (Phase B).
timeFrame: Baseline (last 7 days of Week 4) - End of treatment (last 7 days of Week 17)
measure: Change in Sleep Disruption (Daily 11-point NRS) From Baseline to End of Treatment (Phase B).
timeFrame: Baseline (last 7 days of Week 4) - End of treatment (last 7 days of Week 17)
measure: Change in Spasticity as Measured Using the Modified Ashworth Scale From Baseline to End of Treatment (Phase B).
timeFrame: Baseline (End of Week 4) - End of treatment (End of Week 17)
measure: Change in Motricity Index Score From Baseline to End of Treatment (Phase B)for Affected Limbs.
timeFrame: Baseline (End of Week 4) - End of treatment (End of Week 17)
measure: Change in Timed 10-metre Walk From Baseline to End of Treatment (Phase B).
timeFrame: Baseline (End of Week 4) - End of treatment (End of Week 17)
measure: Subject Global Impressions of Change at End of Treatment (Phase B).
timeFrame: End of Treatment (WeeK 17)
measure: Carer Global Impressions of Change at of Treatment (Phase B).
timeFrame: End of treatment (Week 17)
measure: Carer Ease of Transfer Global Impressions of Change at End of Treatment (Phase B).
timeFrame: End of treatment (week 17)
measure: Physician Global Impressions of Change at End of Treatment (Phase B).
timeFrame: End of treatment (week 17)
measure: Change EuroQoL Quality of Life Questionnaire (EQ-5D)From Baseline to End of Treatment (Phase B)
timeFrame: [Baseline (End of Week 4) - End of treatment (End of Week 17)
measure: Mood Assessment: Change in Beck Depression Inventory - II (BDI-II)From Baseline to End of Treatment (Phase B)
timeFrame: Baseline (End of week 4) - end of treatment (end of week 17)
Other outcomes:
Locations:
city: Cliftonville
country: United Kingdom
facility: Department of Neurology, Northampton General Hospital
state: Northampton
Study officials:
affiliation: Department of Neurology
name: Paul Davies, MRCP, FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Novotna A, Mares J, Ratcliffe S, Novakova I, Vachova M, Zapletalova O, Gasperini C, Pozzilli C, Cefaro L, Comi G, Rossi P, Ambler Z, Stelmasiak Z, Erdmann A, Montalban X, Klimek A, Davies P; Sativex Spasticity Study Group. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex((R)) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol. 2011 Sep;18(9):1122-31. doi: 10.1111/j.1468-1331.2010.03328.x. Epub 2011 Mar 1.