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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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:
NCT00681538
First received: May 19, 2008
Last updated: June 13, 2013
Last verified: June 2013
Results First Received: March 23, 2011  
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
Conditions: Spasticity
Multiple Sclerosis
Interventions: Drug: Sativex®
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Only those subjects who were deemed responders to Sativex from Phase A (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 to enter Phase B of the study.

Reporting Groups
  Description
Sativex (Phase B) contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Placebo (Phase B) Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.

Participant Flow for 2 periods

Period 1:   Phase A- 4 Weeks Single Blind
    Sativex (Phase B)     Placebo (Phase B)  
STARTED     572     0  
COMPLETED     538     0  
NOT COMPLETED     34     0  

Period 2:   Phase B- Responders;12 Week Double-blind
    Sativex (Phase B)     Placebo (Phase B)  
STARTED     124     117  
COMPLETED     109     115  
NOT COMPLETED     15     2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sativex (Phase B) contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Placebo (Phase B) Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Total Total of all reporting groups

Baseline Measures
    Sativex (Phase B)     Placebo (Phase B)     Total  
Number of Participants  
[units: participants]
  124     117     241  
Age [1]
[units: Years]
Mean ± Standard Deviation
  49.1  ± 9.09     48.1  ± 9.59     48.6  ± 9.33  
Gender  
[units: Participants]
     
Female     72     73     145  
Male     52     44     96  
Duration of Multiple Sclerosis Phase B [2]
[units: years]
Mean ± Standard Deviation
  13.3  ± 8.29     11.8  ± 7.38     12.6  ± 7.88  
Duration of Spasticity Phase B [2]
[units: years]
Mean ± Standard Deviation
  8.6  ± 6.89     6.7  ± 5.40     7.7  ± 6.27  
Expanded Disability Status Scale (EDSS)- Phase B [3]
[units: Score]
Mean ± Standard Deviation
  6.5  ± 1.46     6.0  ± 1.44     6.0  ± 1.45  
Baseline Spasticity numerical rating scale (NRS) Score Phase B [4]
[units: Score]
Mean ± Standard Deviation
  3.87  ± 1.49     3.92  ± 1.55     3.90  ± 1.51  
[1] Of the 572 subjects who entered Phase A, 241 entered Phase B; 124 randomised to Sativex and 117 to placebo. The data below details that for Phase B.
[2] Of the 572 subjects who entered Phase A, 241 entered Phase B; 124 randomised to Sativex and 117 to placebo.
[3] 241 entered Phase B; 124 randomised to Sativex and 117 to placebo. EDSS is a method of quantifying disability in multiple sclerosis.The EDSS quantifies disability in eight Functional Systems (FS) and allows neurologists to assign a Functional System Score in each of these. EDSS steps 1.0 to 4.5 refer to people with MS who are fully ambulatory. EDSS steps 5.0 to 9.5 are defined by the impairment to ambulation. Each score is given a definition and thus can identify for the subject their score depending on their condition e.g. score of 1.0: No disability, minimal signs on 1 FS.
[4]

Of the 572 subjects who entered Phase A, 241 entered Phase B; 124 randomised to Sativex and 117 to placebo.

Subjects were asked “On a scale of ‘0 to 10’ please indicate the average level of your spasticity over the last 24 hours” with the anchors: 0 = ‘no spasticity’ and 10 = ‘worst possible spasticity’. They were asked to relate ‘no spasticity’ to the time prior to the onset of their spasticity.




  Outcome Measures
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1.  Primary:   The Change in Mean Spasticity Numerical Rating Scale (NRS) Score From Baseline to End of Treatment (Phase B).   [ Time Frame: Baseline (last 7 days of Week 4) - End of treatment (last 7 days of Week 17) ]

2.  Secondary:   Number of Subjects Showing an Improvement of at Least 30% or 50% in Their Mean NRS Spasticity Score (Phase B) From Baseline.   [ Time Frame: Baseline (Day 1) - End of treatment (last 7 days of Week 17) ]

3.  Secondary:   Change in Spasm Frequency (Number of Spasms Per Day) From Baseline to End of Treatment (Phase B).   [ Time Frame: Baseline (last 7 days of Week 4) - End of treatment (last 7 days of Week 17) ]

4.  Secondary:   Change in Sleep Disruption (Daily 11-point NRS) From Baseline to End of Treatment (Phase B).   [ Time Frame: Baseline (last 7 days of Week 4) - End of treatment (last 7 days of Week 17) ]

5.  Secondary:   Change in Spasticity as Measured Using the Modified Ashworth Scale From Baseline to End of Treatment (Phase B).   [ Time Frame: Baseline (End of Week 4) - End of treatment (End of Week 17) ]

6.  Secondary:   Change in Motricity Index Score From Baseline to End of Treatment (Phase B)for Affected Limbs.   [ Time Frame: Baseline (End of Week 4) - End of treatment (End of Week 17) ]

7.  Secondary:   Change in Timed 10-metre Walk From Baseline to End of Treatment (Phase B).   [ Time Frame: Baseline (End of Week 4) - End of treatment (End of Week 17) ]

8.  Secondary:   Subject Global Impressions of Change at End of Treatment (Phase B).   [ Time Frame: End of Treatment (WeeK 17) ]

9.  Secondary:   Carer Global Impressions of Change at of Treatment (Phase B).   [ Time Frame: End of treatment (Week 17) ]

10.  Secondary:   Carer Ease of Transfer Global Impressions of Change at End of Treatment (Phase B).   [ Time Frame: End of treatment (week 17) ]

11.  Secondary:   Physician Global Impressions of Change at End of Treatment (Phase B).   [ Time Frame: End of treatment (week 17) ]

12.  Secondary:   Change EuroQoL Quality of Life Questionnaire (EQ-5D)From Baseline to End of Treatment (Phase B)   [ Time Frame: [Baseline (End of Week 4) - End of treatment (End of Week 17) ]

13.  Secondary:   Mood Assessment: Change in Beck Depression Inventory - II (BDI-II)From Baseline to End of Treatment (Phase B)   [ Time Frame: Baseline (End of week 4) - end of treatment (end of week 17) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Richard Potts, Clinical Operations Director
Organization: GW Pharma Ltd
phone: +44 1353 616600
e-mail: rp@gwpham.com


Publications of Results:

Responsible Party: GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT00681538     History of Changes
Other Study ID Numbers: GWSP0604
Study First Received: May 19, 2008
Results First Received: March 23, 2011
Last Updated: June 13, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Czech Republic: State Institute for Drug Control
Spain: Spanish Agency of Medicines
Italy: Ethics Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Germany: Federal Institute for Drugs and Medical Devices