Back to resultsSativex Versus Placebo When Added to Existing Treatment for Central Neuropathic Pain in MS
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Sativex
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis focused on measuring Central Neuropathic Pain
Eligibility Criteria
Inclusion Criteria:
- Any disease sub-type of MS of at least two years duration
- Central neuropathic pain (CNP) of at least three months and expected to remain stable for the study duration
- Moderate CNP defined by NRS pain score at baseline sum to at least 24
- Subject established on or previously tried and failed analgesic therapy for CNP
- If receiving disease modifying medications, stable dose for 3 months and maintained for study duration
Exclusion Criteria:
- Subjects whose identified pain is likely to be nociceptive, musculoskeletal (including spasms) peripheral neuropathic or psychogenic in origin, or due to trigeminal neuralgia.
- Other non central neuropathic pain of a severity which is likely to interfere with the patients assessment of CNP
- medical history suggests subject is likely to relapse/remit during course of study
- history of schizophrenia (including family history), other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with MS
- known or suspected history of alcohol abuse, epilepsy or recurrent seizures or hypersensitivity to cannabinoids
- travel outside of the country of residence planned during the study
- significant cardiac, renal or hepatic impairment
- subjects with current recreational cannabis, medicinal cannabis or synthetic cannabinoid based medications within 3 months prior to study entry and unwilling to abstain for the duration of the study
Sites / Locations
- Multiple Sclerosis Program, Foothills Hospital SSB
- MS Clinic, UBC Purdy Pavilion
- Dalhousie MS Research Clinic
- London Health Sciences Centre / University Hospital
- Ottawa Hospital General Campus
- Montreal Neurological Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
A
B
Arm Description
Outcomes
Primary Outcome Measures
Change in Mean Pain Due to MS NRS Score
The pain NRS 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 pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to multiple sclerosis. A negative value indicates an improvement in pain score from baseline.
Number of Patients With at Least 30% Improvement in Numerical Rating Scale (NRS) Pain Score From Baseline
A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS pain score from baseline to week 14 (last 7 days). The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to multiple sclerosis. The pain NRS was completed at the same time each day, i.e. bedtime in the evening.
Secondary Outcome Measures
Change in Pain From Baseline to End of the Treatment Using the NPS (Neuropathic Pain Scale)
The NPS score is 0-100 sum of 10 individual pain scores (0-10 NRS, 0= no pain to 10 = most pain imaginable). A negative change from baseline indicates an improvement in pain.
Change From Baseline to End of Treatment in Break-through Analgesia Usage
Use of break through medication was recorded daily during the 14 weeks of the study as the number of paracetamol tablets taken. The change in mean daily quantities of tablets used was calculated from baseline to the last seven days of treatment.
Change From Baseline to End of Treatment in BPI (Brief Pain Inventory) Short Form
The BPI-SF is a 14-item questionnaire that asks patients to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items(range 0-10). The minimum value is zero and maximum is 10. A higher score represents a poor outcome.
Change in Subject Global Impression of Change (SGIC)
A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain due to multiple sclerosis 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 baseline subjects wrote a brief description of their pain caused by multiple sclerosis which was used at Week 14 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Change in Sleep Disruption NRS
The sleep disruption NRS 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 how your pain disrupted your sleep last night?" where 0 = did not disrupt sleep and 10 = completely disrupted (unable to sleep at all). A negative value indicates an improvement in sleep disruption score from baseline.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00391079
Brief Title
Sativex Versus Placebo When Added to Existing Treatment for Central Neuropathic Pain in MS
Official Title
A Double Blind, Randomised, Placebo Controlled, Parallel Group Study of Sativex When Added to the Existing Treatment Regimen, in the Relief of Central Neuropathic Pain in Subjects With Multiple Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
September 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jazz Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to find out if cannabis-based medicine compared to a dummy medicine (placebo that contains no active ingredient) can help the central neuropathic pain patients experience as a result of multiple sclerosis. This type of pain "central neuropathic pain" is described as shooting, stabbing, burning or searing like sensation, which is often worse at night.
Detailed Description
GW has shown in phase II and III studies that Sativex has analgesic properties that are effective in relieving neuropathic pain. These studies suggested that Sativex is well tolerated and may also improve sleep and quality of life. GW is conducting this study to further demonstrate these effects.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Central Neuropathic Pain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
339 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Experimental
Arm Title
B
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Sativex
Other Intervention Name(s)
GW-1000-02
Intervention Description
Containing D9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.
Delivered in 100 µl actuations by a pump action oromucosal spray. Maximum dose within any 24-hour interval 12 sprays (THC 32.5 mg: CBD 30 mg.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
GA0034
Intervention Description
Containing colourants and excipients. Delivered in 100 µl actuations by a pump action oromucosal spray. Maximum dose within any 24-hour interval 12 sprays.
Primary Outcome Measure Information:
Title
Change in Mean Pain Due to MS NRS Score
Description
The pain NRS 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 pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to multiple sclerosis. A negative value indicates an improvement in pain score from baseline.
Time Frame
14 weeks: Baseline - End of Treatment (last 7 days of treatment)
Title
Number of Patients With at Least 30% Improvement in Numerical Rating Scale (NRS) Pain Score From Baseline
Description
A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS pain score from baseline to week 14 (last 7 days). The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to multiple sclerosis. The pain NRS was completed at the same time each day, i.e. bedtime in the evening.
Time Frame
14 weeks: Baseline - end of treatment (last 7 days)
Secondary Outcome Measure Information:
Title
Change in Pain From Baseline to End of the Treatment Using the NPS (Neuropathic Pain Scale)
Description
The NPS score is 0-100 sum of 10 individual pain scores (0-10 NRS, 0= no pain to 10 = most pain imaginable). A negative change from baseline indicates an improvement in pain.
Time Frame
14 weeks: Baseline - End of treatment (Week 14)
Title
Change From Baseline to End of Treatment in Break-through Analgesia Usage
Description
Use of break through medication was recorded daily during the 14 weeks of the study as the number of paracetamol tablets taken. The change in mean daily quantities of tablets used was calculated from baseline to the last seven days of treatment.
Time Frame
14 weeks: baseline - end of treatment (last 7 days)
Title
Change From Baseline to End of Treatment in BPI (Brief Pain Inventory) Short Form
Description
The BPI-SF is a 14-item questionnaire that asks patients to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items(range 0-10). The minimum value is zero and maximum is 10. A higher score represents a poor outcome.
Time Frame
14 weeks: Baseline to end of treatment (last 7 days of treatment)
Title
Change in Subject Global Impression of Change (SGIC)
Description
A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain due to multiple sclerosis 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 baseline subjects wrote a brief description of their pain caused by multiple sclerosis which was used at Week 14 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Time Frame
Week 14
Title
Change in Sleep Disruption NRS
Description
The sleep disruption NRS 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 how your pain disrupted your sleep last night?" where 0 = did not disrupt sleep and 10 = completely disrupted (unable to sleep at all). A negative value indicates an improvement in sleep disruption score from baseline.
Time Frame
14 weeks; Baseline to end of treatment (last 7 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Any disease sub-type of MS of at least two years duration
Central neuropathic pain (CNP) of at least three months and expected to remain stable for the study duration
Moderate CNP defined by NRS pain score at baseline sum to at least 24
Subject established on or previously tried and failed analgesic therapy for CNP
If receiving disease modifying medications, stable dose for 3 months and maintained for study duration
Exclusion Criteria:
Subjects whose identified pain is likely to be nociceptive, musculoskeletal (including spasms) peripheral neuropathic or psychogenic in origin, or due to trigeminal neuralgia.
Other non central neuropathic pain of a severity which is likely to interfere with the patients assessment of CNP
medical history suggests subject is likely to relapse/remit during course of study
history of schizophrenia (including family history), other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with MS
known or suspected history of alcohol abuse, epilepsy or recurrent seizures or hypersensitivity to cannabinoids
travel outside of the country of residence planned during the study
significant cardiac, renal or hepatic impairment
subjects with current recreational cannabis, medicinal cannabis or synthetic cannabinoid based medications within 3 months prior to study entry and unwilling to abstain for the duration of the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerard S Barron, BSc
Organizational Affiliation
GW Pharma Ltd
Official's Role
Study Director
Facility Information:
Facility Name
Multiple Sclerosis Program, Foothills Hospital SSB
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 2T9
Country
Canada
Facility Name
MS Clinic, UBC Purdy Pavilion
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 2B5
Country
Canada
Facility Name
Dalhousie MS Research Clinic
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V8
Country
Canada
Facility Name
London Health Sciences Centre / University Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Ottawa Hospital General Campus
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Montreal Neurological Institute
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3 A 2B4
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
23180178
Citation
Langford RM, Mares J, Novotna A, Vachova M, Novakova I, Notcutt W, Ratcliffe S. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. J Neurol. 2013 Apr;260(4):984-97. doi: 10.1007/s00415-012-6739-4. Epub 2012 Nov 21.
Results Reference
result
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Sativex Versus Placebo When Added to Existing Treatment for Central Neuropathic Pain in MS
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