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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:
NCT00391079
First received: October 20, 2006
Last updated: June 13, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
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, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GW Pharmaceuticals Ltd.:

Primary Outcome Measures:
  • Change in Mean Pain Due to MS NRS Score [ Time Frame: 14 weeks: Baseline - End of Treatment (last 7 days of treatment) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 weeks: Baseline - end of treatment (last 7 days) ] [ Designated as safety issue: No ]
    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) [ Time Frame: 14 weeks: Baseline - End of treatment (Week 14) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 weeks: baseline - end of treatment (last 7 days) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 weeks: Baseline to end of treatment (last 7 days of treatment) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 14 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 weeks; Baseline to end of treatment (last 7 days) ] [ Designated as safety issue: No ]
    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.


Enrollment: 339
Study Start Date: September 2006
Study Completion Date: September 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Sativex

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.

Other Name: GW-1000-02
Placebo Comparator: B Drug: Placebo
Containing colourants and excipients. Delivered in 100 µl actuations by a pump action oromucosal spray. Maximum dose within any 24-hour interval 12 sprays.
Other Name: GA0034

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00391079

Locations
Canada, Alberta
Multiple Sclerosis Program, Foothills Hospital SSB
Calgary, Alberta, Canada, T2N 2T9
Canada, British Columbia
MS Clinic, UBC Purdy Pavilion
Vancouver, British Columbia, Canada, V6T 2B5
Canada, Nova Scotia
Dalhousie MS Research Clinic
Halifax, Nova Scotia, Canada, B3H 1V8
Canada, Ontario
London Health Sciences Centre / University Hospital
London, Ontario, Canada, N6A 5A5
Ottawa Hospital General Campus
Ottawa, Ontario, Canada, K1H 8L6
Canada, Quebec
Montreal Neurological Institute
Montreal, Quebec, Canada, H3 A 2B4
Sponsors and Collaborators
GW Pharmaceuticals Ltd.
Investigators
Study Director: Gerard S Barron, BSc GW Pharma Ltd
  More Information

Publications:
Responsible Party: GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT00391079     History of Changes
Other Study ID Numbers: GWMS0501
Study First Received: October 20, 2006
Results First Received: May 30, 2012
Last Updated: June 13, 2013
Health Authority: Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Czech Republic: State Institute for Drug Control

Keywords provided by GW Pharmaceuticals Ltd.:
Central Neuropathic Pain

Additional relevant MeSH terms:
Multiple Sclerosis
Neuralgia
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Neurologic Manifestations
Neuromuscular Diseases
Pain
Pathologic Processes
Peripheral Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on October 23, 2014