Clinical trial NCT01599234: A Study to Evaluate the Efficacy of Sativex in Relieving Symptoms of Spasticity Due to Multiple Sclerosis
Official title: A Double Blind, Randomised, Placebo Controlled, Parallel Group Study of Sativex, in Subjects With Symptoms of Spasticity Due to Multiple Sclerosis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-05-15
Enrollment: 337
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to assess the efficacy of Sativex in relieving symptoms of spasticity in multiple sclerosis

Detailed description: This was a 15 week (one week baseline and fourteen weeks treatment period), multicentre, double blind, randomised, placebo controlled, parallel group study to evaluate the efficacy of Sativex in subjects with symptoms of spasticity due to multiple sclerosis. Eligible subjects entered a seven day baseline period. Subjects then returned to the centre for randomisation and dose introduction. Visits occurred at the end of treatment weeks two, six, ten and at the end of the study (treatment week 14) or earlier if they withdrew.

Eligibility criteria: Inclusion Criteria:

* Willing and able to give informed consent.
* Aged 18 years or above.
* Ability (in the investigator's opinion) and willingness to comply with all study requirements.
* Diagnosed with any disease subtype of multiple sclerosis of duration greater than six months.
* Diagnosed with spasticity due to multiple sclerosis of at least three months duration and was not wholly relieved with their current therapy.
* Stable dose of anti-spasticity and non-pharmacological therapies for at least 30 days prior to the screening visit and willingness for these to be maintained for the duration of the study.
* Stable dose of disease modifying medications for at least six months duration prior to the screening visit and willingness to maintain this for the duration of the study.
* The last six daily diary spasticity numerical rating scale scores before randomisation had been completed and summed to at least 24.
* Agreement for the responsible authorities (as applicable in individual countries), their primary care physician, and their consultant, if appropriate, to be notified of their participation in the study.

Exclusion Criteria:

* Concomitant disease or disorder that had symptoms of spasticity, or that may have influenced the subject's level of spasticity.
* Received a Botulinum Toxin injection within four months prior to the screening visit or unwillingness to stop receiving Botulinum Toxin injections for the relief of spasticity for the duration of the study.
* Had used cannabis within 30 days of study entry and unwillingness to abstain for the duration for the study.
* Had used cannabinoid based medications within 60 days of study entry and unwillingness to abstain for the duration for the study.
* History of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
* Known or suspected history of alcohol or substance abuse.
* History of epilepsy or recurrent seizures.
* Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medication.
* Experienced myocardial infarction or clinically relevant cardiac dysfunction within the last 12 months or had a cardiac disorder that, in the opinion of the investigator would put the subject at risk of a clinically relevant arrhythmia or myocardial infarction.
* QT interval of \> 450 ms (males) or \> 470 ms (females) at Visit 1.
* Secondary to tertiary arterial ventricular block or sinus bradycardia (heart rate \< 50 bpm) or sinus tachycardia (heart rate \> 110 bpm) at Visit 1.
* Diastolic blood pressure of \< 50 mmHg or \> 105 mmHg in a sitting position at rest for 5 minutes prior to randomisation.
* Impaired renal function i.e. serum creatinine clearance is lower than 50 ml/min at Visit 1.
* Significantly impaired hepatic function, at Visit 1, in the investigator's opinion and/or had liver function tests of equal to or greater than three times the upper limit of normal.
* Female subjects of child bearing potential and male subjects whose partner was of child bearing potential, unless were willing to ensure that they or their partner used effective contraception during the study and for three months thereafter.
* If female, were pregnant or lactating, or were planning pregnancy during the course of the study and for three months thereafter.
* 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, may influence the result of the study, or the subject's ability to participate in the study.
* Following a physical examination, the subject had any abnormalities that, in the opinion of the investigator, would prevent the subject from safely participating in the study.
* Scheduled elective surgery or other procedures, which required general anaesthesia during the study.
* Intention to donate blood during the study.
* Intention to travel internationally during the study.
* Previous randomisation into this study.

Primary outcomes:
measure: Change From Baseline in Mean Spasticity 0-10 Numerical Rating Scale (NRS) Score During the Last 14 Day of Treatment (End of Treatment)
timeFrame: 0-15 weeks
Secondary outcomes:
measure: Number of Subjects With a 30% or Greater Improvement in Mean Spasticity 0-10 NRS Score at the End of Treatment Compared to Baseline
timeFrame: 0-15 weeks
measure: Change From Baseline in the Mean Modified Ashworth Scale Score at the End of Treatment
timeFrame: Day 0 (Randomisation) and Day 99 (End of Treatment)
measure: Change From Baseline in Mean Sleep Quality 0-10 NRS During the Last 14 Days of Treatment (End of Treatment)
timeFrame: 0-15 weeks
measure: Incidence of Adverse Events as a Measure of Subject Safety
timeFrame: 0-15 weeks
measure: Change From Baseline in Mean Timed 10 Metre Walk Time at the End of Treatment
timeFrame: Day 0 (Randomisation) and Day 99 (End of Treatment)
measure: Carer Global Impression of Change at the End of Treatment
timeFrame: Day 99 (end of treatment)
measure: Change From Baseline in the Mean Total Barthel Activities of Daily Living Index Score at the End of Treatment
timeFrame: Day 0 (Randomisation) and Day 99 (End of Treatment)
measure: Number of Subjects With a 50% or Greater Improvement in Mean Spasticity 0-10 NRS Score at the End of Treatment Compared to Baseline
timeFrame: 0 - 15 weeks
Other outcomes:
Locations:
city: Reading
country: United Kingdom
facility: The Royal Berkshire and Battle Hospitals NHS Trust
Study officials:
affiliation: The Royal Berkshire and Battle Hospitals NHS Trust, London Road, Reading, Berkshire, RG1 5AN.
name: Christine Collin
role: PRINCIPAL_INVESTIGATOR
References:
citation: Collin C, Ehler E, Waberzinek G, Alsindi Z, Davies P, Powell K, Notcutt W, O'Leary C, Ratcliffe S, Novakova I, Zapletalova O, Pikova J, Ambler Z. A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol Res. 2010 Jun;32(5):451-9. doi: 10.1179/016164109X12590518685660. Epub 2010 Mar 19.
citation: Di Marzo V, Centonze D. Placebo effects in a multiple sclerosis spasticity enriched clinical trial with the oromucosal cannabinoid spray (THC/CBD): dimension and possible causes. CNS Neurosci Ther. 2015 Mar;21(3):215-21. doi: 10.1111/cns.12358. Epub 2014 Dec 4.