Clinical trial NCT00711646: A Study of Sativex® for Relief of Spasticity in Subjects With Multiple Sclerosis.
Official title: A Double Blind, Randomised, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Cannabis Based Medicine 1:1 THC:CBD Compared With Placebo for the Treatment of Spasticity in Patients With Multiple Sclerosis.
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: 2008-07-09
Enrollment: 189
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 evaluate the efficacy, safety and tolerability of Sativex® in subjects diagnosed with MS and spasticity.

Detailed description: This was an eight week (two weeks baseline, six weeks treatment), multicentre, double blind, randomised, placebo controlled parallel group study to evaluate the efficacy, safety and tolerability of Sativex® in subjects diagnosed with MS and spasticity. Subjects were screened to determine eligibility and completed a two week baseline period. Subjects then returned to the site for assessment, randomisation and dose introduction. Visits occurred at the end of treatment week two and at the end of the study (treatment week six) or withdrawal.

Eligibility criteria: Inclusion Criteria:

* Willing and able to give informed consent.
* Male or female, aged 18 years or above.
* Stable disease for at least three months prior to study entry, in the opinion of the investigator.
* Diagnosed with MS whose spasticity was not wholly relieved with the therapy at the time of study entry.
* Significant spasticity in at least two muscle groups defined as a score of two or more on the Ashworth Scale for each muscle group.
* Stable dose of current anti-spasticity medication for at least 30 days prior to study entry.
* Willing to maintain a stable dose of anti-spasticity medication and level of physiotherapy for the duration of the study.
* Clinically acceptable laboratory results at Visit 2.
* Willing, if female and of child bearing potential or male subjects with a partner of child bearing potential, to ensure that effective contraception was used during the study and for three months thereafter.
* No cannabinoid use (cannabis, Marinol® or Nabilone) for at least seven days before Visit 1 and were willing to abstain from any use of cannabis during the study.
* Able (in the investigators opinion) and willing to comply with all study requirements.
* Willing for the Home Office to be notified of his or her participation in the study (applicable to the UK centres only).
* Willing to allow his or her GP and consultant, if appropriate, to be notified of participation in the study.

Exclusion Criteria:

* History of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
* Known history of alcohol or substance abuse.
* Severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias, poorly controlled hypertension or severe heart failure.
* History of epilepsy.
* Female subject who was pregnant, lactating or planning pregnancy during the course of the study.
* Significant renal or hepatic impairment.
* Scheduled elective surgery or other procedures requiring general anaesthesia during the study.
* Subject who was terminally ill or was inappropriate for placebo medication.
* Any other significant disease or disorder which, in the opinion of the investigator, either put the subject at risk because of participation in the study, or influenced the result of the study, or the subject's ability to participate in the study.
* Regular levodopa (Sinemet®, Sinemet Plus®, Levodopa, L-dopa, Madopar®, Benserazide) therapy within seven days of study entry.
* Male subject receiving sildenafil (Viagra®) and unwilling to stop medication for the duration of the study.
* Subjects who were taking fentanyl (Durogesic®, Actiq®)
* Subjects who were taking antiarrhythmic medications.
* Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medications.
* Known or suspected adverse reaction to cannabinoids.
* Planned travel outside the UK during the study (applicable to the UK centres only).
* Donation of blood during the study.
* Subjects who had participated in another research study in the 12 weeks prior to study entry.
* Subjects previously randomised into this study.

Primary outcomes:
measure: Assessment of Change From Baseline in the Mean Spasticity 0-10 Numerical Rating Scale Score.
timeFrame: 0-52 days
Secondary outcomes:
measure: Change From Baseline in Mean Ashworth Scale Score at the End of Treatment
timeFrame: Days 0 - 52
measure: Change From Baseline in Mean Spasm Frequency Score at the End of Treatment
timeFrame: Days 0 - 52
measure: Change From Baseline in Mean Motricity Index Score for the Arms
timeFrame: Day 7 and 52
measure: Patient's Global Impression of Change in Condition at the End of Treatment
timeFrame: Day 52
measure: Incidence of Adverse Events as a Measure of Subject Safety
timeFrame: Day 0-52
measure: Change From Baseline in Mean Motricity Index Score for the Legs
timeFrame: Day 7 and Day 52
Other outcomes:
Locations:
city: Reading
country: United Kingdom
facility: Royal Berkshire Hospital
state: Oxfordshire
Study officials:
affiliation: Royal Berkshire Hospital
name: Christine Collin, MB BS MRCP FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Collin C, Davies P, Mutiboko IK, Ratcliffe S; Sativex Spasticity in MS Study Group. Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur J Neurol. 2007 Mar;14(3):290-6. doi: 10.1111/j.1468-1331.2006.01639.x.
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.