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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:
NCT00711646
First received: July 8, 2008
Last updated: June 13, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to evaluate the efficacy, safety and tolerability of Sativex® in subjects diagnosed with MS and spasticity.


Condition Intervention Phase
Spasticity
Multiple Sclerosis
Drug: Sativex®
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
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.

Resource links provided by NLM:


Further study details as provided by GW Pharmaceuticals Ltd.:

Primary Outcome Measures:
  • Assessment of Change From Baseline in the Mean Spasticity 0-10 Numerical Rating Scale Score. [ Time Frame: 0-52 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in Mean Ashworth Scale Score at the End of Treatment [ Time Frame: Days 0 - 52 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 189
Study Start Date: June 2002
Study Completion Date: March 2004
Primary Completion Date: March 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sativex 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
Placebo Comparator: Placebo 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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00711646

Locations
United Kingdom
Royal Berkshire Hospital
Reading, Oxfordshire, United Kingdom, RG1 5AN
Sponsors and Collaborators
GW Pharmaceuticals Ltd.
Investigators
Principal Investigator: Christine Collin, MB BS MRCP FRCP Royal Berkshire Hospital
  More Information

Publications:
Responsible Party: GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT00711646     History of Changes
Other Study ID Numbers: GWMS0106
Study First Received: July 8, 2008
Results First Received: July 11, 2012
Last Updated: June 13, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Romania: National Medicines Agency

Keywords provided by GW Pharmaceuticals Ltd.:
Spasticity
Multiple Sclerosis

Additional relevant MeSH terms:
Muscle Spasticity
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Signs and Symptoms
Pathologic Processes

ClinicalTrials.gov processed this record on August 28, 2014