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A Study of Sativex® for Relief of Spasticity in Subjects With Multiple Sclerosis.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00711646
Recruitment Status : Completed
First Posted : July 9, 2008
Results First Posted : September 14, 2012
Last Update Posted : June 24, 2013
Sponsor:
Information provided by (Responsible Party):
GW Pharmaceuticals Ltd.

Tracking Information
First Submitted Date  ICMJE July 8, 2008
First Posted Date  ICMJE July 9, 2008
Results First Submitted Date  ICMJE July 11, 2012
Results First Posted Date  ICMJE September 14, 2012
Last Update Posted Date June 24, 2013
Study Start Date  ICMJE June 2002
Actual Primary Completion Date March 2004   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2012)
Assessment of Change From Baseline in the Mean Spasticity 0-10 Numerical Rating Scale Score. [ Time Frame: 0-52 days ]
The spasticity Numerical Rating Scale was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your average spasticity in the last 24 hours" where 0 = no spasticity and 10 = worst ever spasticity. For the analysis, end of treatment was defined as the mean of the last seven days in the study or the last three days if the subject withdrew due to worsening spasticity or lack of efficacy. A negative value indicates an improvement in spasticity score from baseline.
Original Primary Outcome Measures  ICMJE
 (submitted: July 8, 2008)
Assessment of change from baseline in the mean spasticity 0-10 NRS score. [ Time Frame: 0-52 days ]
Change History Complete list of historical versions of study NCT00711646 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2012)
  • Change From Baseline in Mean Ashworth Scale Score at the End of Treatment [ Time Frame: Days 0 - 52 ]
    The mean Ashworth Scale score across muscle groups was calculated using only those muscle groups with a score of greater than or equal to two at baseline. All 20 muscle groups were assessed for spasticity (using a 1-5 scale): 1= no increase in muscle tone to 5= passive movement is difficult and affected part is rigid in flexion or extension. The score for all 20 muscle groups were added to give a total score out of 100; minimum score was 20. A decrease in score indicates an improvement in condition.
  • Change From Baseline in Mean Spasm Frequency Score at the End of Treatment [ Time Frame: Days 0 - 52 ]
    Each day subjects recorded in their diary the frequency of their spasms using the following scoring system: 0 = no spasms, 1 = one or fewer spasms per day, 2 = between one and five spasms per day, 3 = six to nine spasms per day, 4 = ten or more spasms per day or continuous contraction. For the analysis, end of treatment was defined as the mean of the last seven days in the study or the last three days if the subject withdrew due to worsening spasticity or lack of efficacy.
  • Change From Baseline in Mean Motricity Index Score for the Arms [ Time Frame: Day 7 and 52 ]
    Arm - 3 movements were pinch grip, elbow flexion and shoulder abduction. The total arm score was the addition of the score for the 3 arm movements. One point was then added to give a maximum score of 100; minimum was 1 point. Where both arms were assessed, the average of the two limbs scores was used as the assessment score; otherwise the affected limb total score was used. An increase in score indicates an improvement in condition..
  • Patient's Global Impression of Change in Condition at the End of Treatment [ Time Frame: Day 52 ]
    A 7-point Likert-type scale was used, with the question: 'Please assess the change in your condition since entry into the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their condition which was used at end of treatment to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
  • Incidence of Adverse Events as a Measure of Subject Safety [ Time Frame: Day 0-52 ]
    The number of subjects who reported an adverse event during the course of the study is presented.
  • Change From Baseline in Mean Motricity Index Score for the Legs [ Time Frame: Day 7 and Day 52 ]
    Ankle dorsiflexion, knee extension and hip flexion were assessed and scored to give a maximum of 100%. The Motricity Index score (scale 1-100) was recorded for limbs that had an associated Ashworth Scale score, which was greater than or equal to two at baseline.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2008)
  • Ashworth Scale [ Time Frame: Days 0, 14, 28 and 52 ]
  • Spasm frequency scores [ Time Frame: Day 0-52 ]
  • Motricity Index scores [ Time Frame: Day 7 and 52 ]
  • Patient's Global Impression of Change in Condition [ Time Frame: Day 7 and 52 ]
  • Adverse Events [ Time Frame: Day 0-52 ]
  • Oral examination [ Time Frame: Day 7 and 52 ]
  • Clinical Laboratory [ Time Frame: Day 7 and 52 ]
  • vital signs [ Time Frame: Day 0-52 ]
  • intoxication level [ Time Frame: Day 0-52 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Sativex® for Relief of Spasticity in Subjects With Multiple Sclerosis.
Official Title  ICMJE 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Spasticity
  • Multiple Sclerosis
Intervention  ICMJE
  • Drug: Sativex®
    containing THC (27 mg/ml):CBD (25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Maximum permitted dose was eight actuations in any three hour period and 24 actuations (THC 65 mg: CBD 60 mg) in 24 hours
    Other Name: GW-1000-02
  • Drug: Placebo
    containing peppermint oil, 0.05% (v/v), quinoline yellow, 0.005% (w/v), sunset yellow, 0.0025% (w/v), in ethanol:propylene glycol (50:50) excipient.
    Other Name: GW-4001-01
Study Arms  ICMJE
  • Experimental: Sativex
    Intervention: Drug: Sativex®
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 8, 2008)
189
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2004
Actual Primary Completion Date March 2004   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00711646
Other Study ID Numbers  ICMJE GWMS0106
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GW Pharmaceuticals Ltd.
Study Sponsor  ICMJE GW Pharmaceuticals Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christine Collin, MB BS MRCP FRCP Royal Berkshire Hospital
PRS Account GW Pharmaceuticals Ltd.
Verification Date June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP