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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A | Experimental |
| |
| B | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sativex | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 14 weeks: Baseline - End of Treatment (last 7 days of treatment) |
| 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. | 14 weeks: Baseline - end of treatment (last 7 days) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 14 weeks: Baseline - End of treatment (Week 14) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gerard S Barron, BSc | GW Pharma Ltd | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Multiple Sclerosis Program, Foothills Hospital SSB | Calgary | Alberta | T2N 2T9 | Canada | ||
| MS Clinic, UBC Purdy Pavilion |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23180178 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sativex | Range of 8 -12 sprays per day. Each actuation of oromucosal spray delivers 2.7 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD). Thus maximum daily dose is 32.4 mg THC and 30 mg CBD. |
| FG001 | Placebo | Range of 8-12 sprays per day of placebo spray. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sativex | Range of 8 -12 sprays per day. Each actuation of oromucosal spray delivers 2.7 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD). Thus maximum daily dose is 32.4 mg THC and 30 mg CBD. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Change in mean daily NRS score | Posted | Mean | Standard Deviation | units on a scale | 14 weeks: Baseline - End of Treatment (last 7 days of treatment) |
|
All adverse events occurring from time of consent to post study follow up i.e. 15 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medications were also collected/
All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sativex | Range of 8 -12 sprays per day. Each actuation of oromucosal spray delivers 2.7 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD). Thus maximum daily dose is 32.4 mg THC and 30 mg CBD. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA (10.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Richard Potts Clinical Operations Director | GW Pharmaceuticals | +44 1223 266800 | rp@gwpharm.com |
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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| ID | Term |
|---|---|
| C587251 | nabiximols |
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|
| Placebo | Drug | Containing colourants and excipients. Delivered in 100 µl actuations by a pump action oromucosal spray. Maximum dose within any 24-hour interval 12 sprays. |
|
|
| 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. |
| 14 weeks: baseline - end of treatment (last 7 days) |
| 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. | 14 weeks: Baseline to end of treatment (last 7 days of treatment) |
| 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. | Week 14 |
| 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. | 14 weeks; Baseline to end of treatment (last 7 days) |
| Vancouver |
| British Columbia |
| V6T 2B5 |
| Canada |
| Dalhousie MS Research Clinic | Halifax | Nova Scotia | B3H 1V8 | Canada |
| London Health Sciences Centre / University Hospital | London | Ontario | N6A 5A5 | Canada |
| Ottawa Hospital General Campus | Ottawa | Ontario | K1H 8L6 | Canada |
| Montreal Neurological Institute | Montreal | Quebec | H3 A 2B4 | Canada |
Range of 8-12 sprays per day of placebo spray.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Duration of Multiple Sclerosis (MS) | Mean | Standard Deviation | years |
|
| Duration of Central Neuropathic Pain (CNP) | Mean | Standard Deviation | years |
|
| Baseline Pain Numerical Rating Scale (NRS) score | Pain severity NRS was completed daily by answering the following question: 'On a scale of '0 to 10' please indicate the average level of your nerve pain at your chosen site over the last day', with the anchors: 0='no pain' and 10= 'worst possible pain'. | Mean | Standard Deviation | Points on a scale |
|
| OG001 | Placebo | Range of 8-12 sprays of placebo per day |
|
|
|
| Primary | 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. | Posted | Number | participants | 14 weeks: Baseline - end of treatment (last 7 days) |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | Points on a scale | 14 weeks: Baseline - End of treatment (Week 14) |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | tablets | 14 weeks: baseline - end of treatment (last 7 days) |
|
|
|
|
| Secondary | 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. | All subjects who completed the BPI-short form were included in the analysis. Four subjects from the sativex group and three subjects from the placebo group did not complete the form. | Posted | Mean | Standard Deviation | Points on a scale | 14 weeks: Baseline to end of treatment (last 7 days of treatment) |
|
|
|
|
| Secondary | 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. | All subjects who completed the question were included in the analysis. Two subjects from the Sativex group and six subjects from the placebo group did not complete the question. | Posted | Number | percentage of subjects | Week 14 |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | points on a scale | 14 weeks; Baseline to end of treatment (last 7 days) |
|
|
|
|
| 3 |
| 167 |
| 99 |
| 167 |
| EG001 | Placebo | Range of 8-12 sprays of placebo per day | 2 | 172 | 65 | 172 |
| Constipation | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Motor dysfunction | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Suicidal Ideation | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Vomitting | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Feeling Abnormal | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Memory Impairment | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Balance Disorder | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Psychomotor skills impaired | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
GW will coordinate the dissemination of data from this study and may solicit input and assistance from the principal investigator. All publications for example, manuscripts, abstracts, oral/slide presentations or book chapters based on this study, must be submitted to GW for corporate review before release.
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| Slightly Improved |
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| No Change |
|
| Slightly Worse |
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| Much Worse |
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| Very Much Worse |
|