Sativex Versus Placebo When Added to Existing Treatment for Central Neuropathic Pain in MS

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Sativex
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: Sativex<br>* 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.<br>* Other names: GW-1000-02;|
| Placebo Comparator: B<br> | Drug: Placebo<br>* Containing colourants and excipients. Delivered in 100 µl actuations by a pump action oromucosal spray. Maximum dose within any 24-hour interval 12 sprays.<br>* Other names: GA0034;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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) | 

Secondary Outcome Measures

| Outcome Measure | 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central Neuropathic Pain