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A Study of Cannabis Based Medicine Extracts and Placebo in Patients With Pain Due to Spinal Cord Injury

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01606202
Recruitment Status : Completed
First Posted : May 25, 2012
Results First Posted : September 28, 2012
Last Update Posted : September 28, 2012
Sponsor:
Information provided by (Responsible Party):
GW Pharmaceuticals Ltd.

Tracking Information
First Submitted Date  ICMJE May 21, 2012
First Posted Date  ICMJE May 25, 2012
Results First Submitted Date  ICMJE July 19, 2012
Results First Posted Date  ICMJE September 28, 2012
Last Update Posted Date September 28, 2012
Study Start Date  ICMJE July 2002
Actual Primary Completion Date January 2005   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2012)
Change From Baseline in Mean Central Neuropathic Pain 11-Point Numerical Rating Scale Scores at the End of Treatment (up to 51 Days). [ Time Frame: Up to 51 days ]
The Central Neuropathic Pain Numerical Rating Scale score was recorded three times daily, in the morning (on waking), at lunchtime and in the evening using the scale, 0 = 'No Pain' and 10 = 'Worst Possible Pain'. Patients were instructed to relate 'No Pain' to the time before the start of their spinal cord injury. End of Treatment was defined as the mean of the last seven days in the study or the mean of the last three days if the subject withdrew. A negative value indicates an improvement in pain score from baseline.
Original Primary Outcome Measures  ICMJE
 (submitted: May 23, 2012)
Change from baseline in mean 11-Point Numerical Rating Scale Neuropathic Pain scores at the end of treatment (up to 51 days). [ Time Frame: Up to 51 days ]
Change History Complete list of historical versions of study NCT01606202 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2012)
  • Change From Baseline in the Mean Percentage of Days on Which Escape Medication Was Used at the End of Treatment [ Time Frame: Up to 51 days ]
    The percentage of days that subjects used escape medication was analysed and is presented as the mean change from baseline at the end of treatment. A negative value from baseline indicates an improvement.
  • Change From Baseline in Mean Spasm Severity Numerical Rating Scale Score at the End of Treatment [ Time Frame: Up to 51 days ]
    Each day, just before going to bed, patients recorded in their patient diary whether they experienced any spasms that day and, if yes, recorded the overall level of the spasm(s) experienced using an Numerical Rating Scale spasm scale ranging from 0 = "Mildest ever spasm" to 10 = "Worst ever spasm". The mean spasm severity scores were summarised and analysed analogously to the primary endpoint. A negative value from baseline indicates an improvement.
  • Change From Baseline in the Percentage of Days on Which Spasm Was Experienced at the End of Treatment [ Time Frame: Up to 51 days ]
    Each day, just before going to bed, patients recorded in their patient diary whether they experienced any spasms that day. The percentage of days on which spasm was experienced were summarised and analysed analogously to the primary endpoint. A negative value from baseline indicates an improvement.
  • Change From Baseline in Mean Spasticity Severity Numerical Rating Scale Scores the End of Treatment. [ Time Frame: 0 - 51 days ]
    Each day at bed time patients recorded whether they experienced any spasticity that day and, if yes, the overall level of spasticity experienced was quantified using an Numerical Rating Scale from 0 = "Mildest ever spasticity" to 10 = "Worst ever spasticity". The mean spasticity severity scores and the changes from baseline to End of Treatment were to be calculated. A negative value indicates an improvement from baseline.
  • Change From Baseline in the Percentage of Days on Which Spasticity Was Experienced at the End of Treatment [ Time Frame: Up to 51 days ]
    Each day, just before going to bed, patients recorded in their patient diary whether they had experienced any spasticity that day or not. The percentage of days on which spasticity was experienced (spasticity incidence) was calculated and summarised analogously to the primary efficacy parameter of Numerical Rating Scale pain score. A negative value from baseline indicates an improvement.
  • Change From Baseline in Modified Ashworth Scale Score at the End of Treatment [ Time Frame: Up to 51 days ]
    The Modified Ashworth Scale is a five-point scale conducted on four pre-identified muscle groups. Only the lower limb was assessed because not all Spinal Cord Injury patients upper limb disability. The assessor used the Modified Ashworth scale ranging from 0 ("No increase in muscle tone") to 4 ("Affected part(s) rigid in flexion or extension") to rate the muscle tone for knee and ankle for the left and right sides separately at a pre-dose visit and at the end of treatment. The average of the four individual scores and was taken. A negative value indicates an improvement from baseline.
  • Change From Baseline in the Mean Short Orientation Memory Function Concentration Test Score at the End of Treatment [ Time Frame: Up to 51 days ]
    Patients were asked at baseline and end of treatment, to complete the Short Orientation Memory Function Concentration Test as a measure of cognitive function. The minimum score is 0 and maximum of 28 which denoted good cognitive function . A negative value from baseline indicates a deterioration.
  • Change From Baseline in Mean Spitzer Quality of Life Index Score at the End of Treatment [ Time Frame: Up to 51 days ]
    The Spitzer Quality of Life Index questionnaire consists of five sections, relating to activity, daily living, health, support and outlook. Each section has three choices (numbered 1, 2 and 3) and the patient is required to choose the one that best describes their quality of life during the last week. Choice 1 is scored 2, choice 2 is scored 1 and choice 3 is scored 0. The total Spitzer is the unweighted sum of the five scores. The scale is 0 (bad) to 10 (good). A positive value indicates an improvement from baseline.
  • Change From Baseline in the Mean Caregiver Strain Index Score at the End of Treatment [ Time Frame: Up to 51 days ]
    Carers were asked at baseline and end of treatment to complete the Caregiver Strain Index, as a measure of the strain they felt from being a carer, the maximum possible score being 13. A negative value from baseline indicates an improvement.
  • Number of Subjects Who Reported an Improvement in Their Overall Condition in the Patient Global Impression of Change at the End of Treatment [ Time Frame: Up to 51 days ]
    The Patient Global Impression of Change asked patients to give their impression of the overall change in their condition during the study at the end of treatment using the following scale: 1 = Very Much Improved, 2 = Much Improved, 3 = Minimally Improved, 4 = No Change, 5 = Minimally Worse, 6 = Much Worse, 7 = Very Much Worse. The number of patients who scored their condition as 1, 2, or 3 (improved) is presented.
  • Change From Baseline in the Mean Brief Pain Inventory Score at the End of Treatment [ Time Frame: 0 - 51 days ]
    The Brief Pain Inventory 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 is calculated as the arithmetic mean of the four severity items(range 0-10). A negative value indicates an improvement in worst pain score from baseline.
  • Change From Baseline in the Mean Sleep Disturbance Numerical Rating Scale Score at the End of Treatment [ Time Frame: 0 - 51 days ]
    Each day patients recorded in their patient diary whether they woke during the previous night using the following scoring system: 0 = No, 1 = Once, 2 = Twice, 3 = More than twice, 4 = Awake most of the night. A negative value indicates an improvement from baseline.
  • Incidence of Adverse Events as a Measure of Patient Safety. [ Time Frame: Up to 61 days ]
    The number of patients who experienced an adverse event during the study is presented.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2012)
  • Change from baseline in mean 5 item sleep disturbance scores at the end of treatment (up to 51 days). [ Time Frame: Up to 51 days ]
  • Change from baseline in mean Brief Pain Inventory scores at the end of treatment (up to 51 days) - pain assessment. [ Time Frame: Up to 51 days ]
    The Brief Pain Inventory (BPI) questionnaire was analysed as two series of Numerical Rating Scale-based questions; one series comprised four questions asking subjects to assess their pain levels (pain assessment), the other series comprised seven questions asking subjects to assess the interference of pain on various aspects of their lives (pain interference). The change from baseline in pain assessment scores is presented here.
  • Use of escape medication. [ Time Frame: Up to 51 days ]
    The percentage of days that subjects used escape medication was analysed.
  • Change from baseline in mean Spasm severity Numerical Rating Scale scores at the end of treatment (up to 51 days). [ Time Frame: Up to 51 days ]
  • Change from baseline in mean Spasm incidence to the end of treatment (up to 51 days). [ Time Frame: Up to 51 days ]
  • Change from baseline in mean Spasticity severity Numerical Rating Scale scores the end of treatment (up to 51 days). [ Time Frame: Up to 51 days ]
  • Change from baseline in Spasticity Incidence at the end of treatment (up to 51 days). [ Time Frame: Up to 51 days ]
  • Change from baseline in Modified Ashworth Scale scores at the end of treatment (up to 51 days). [ Time Frame: Up to 51 days ]
    The mean score is a mean of four zero to five scales for each subject, with a maximum possible mean score of five.
  • Change from baseline in Short Orientation Memory Function Concentration Test scores at the end of treatment (up to 51 days). [ Time Frame: Up to 51 days ]
    The maximum possible score was 28 and denoted good cognitive function.
  • Change from baseline in Spitzer Quality of Life Index at the end of treatment (up to 51 days). [ Time Frame: Up to 51 days ]
  • Change from baseline in Caregiver Strain Index scores at the end of treatment (up to 51 days). [ Time Frame: Up to 51 days ]
    Carers were asked at baseline and end of treatment to complete the Caregiven Strain Index, as a measure of the strain they felt from being a carer, the maximum possible score being 13.
  • Patient Global Impression of Change. [ Time Frame: Up to 51 days ]
    The Patient Global Impression of Change consisted of a single question relating to improvement in overall condition since the start of the study and was recorded at the end of the treatment period (up to 51 days).
  • Incidence of Adverse Events as a Measure of Patient Safety. [ Time Frame: Up to 61 days ]
    The number of patients who experienced an adverse event during the study is presented.
  • Change from baseline in mean Brief Pain Inventory scores at the end of treatment (up to 51 days) - pain interference. [ Time Frame: Up to 51 days ]
    The Brief Pain Inventory (BPI) questionnaire was analysed as two series of Numerical Rating Scale-based questions; one series comprised four questions asking subjects to assess their pain levels (pain assessment), the other series comprised seven questions asking subjects to assess the interference of pain on various aspects of their lives (pain interference). The change from baseline in pain interference scores is presented here.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Cannabis Based Medicine Extracts and Placebo in Patients With Pain Due to Spinal Cord Injury
Official Title  ICMJE A Randomised, Double Blind, Placebo Controlled, Parallel Group Comparative Study of the Efficacy, Safety and Tolerability of Sublingual Cannabis Based Medicine Extracts and Placebo in Patients With Intractable Neuropathic Pain Associated With Spinal Cord Injury
Brief Summary A study to investigate the effects of sublingual cannabis based medicine extracts on neuropathic pain associated with spinal cord injury.
Detailed Description This was a multi-centre, double-blind, randomised, placebo-controlled, parallel-group study to evaluate the efficacy and tolerability of GW-1000-02 in central neuropathic pain associated with spinal cord injury. Patients were screened to determine eligibility and completed a seven to 21 day baseline period. Patients then returned to the centre for assessment, randomisation and initial dosing. Visits occurred at the end of treatment week one and at the end of the study (treatment week three) or upon withdrawal. Throughout the study, patients were permitted to take paracetamol as escape analgesic to relieve breakthrough pain. Patients in this study could elect to be screened for an open label extension study of GW-1000-02.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Pain
Intervention  ICMJE
  • Drug: GW-1000-02
    Contained delta-9-tetrahydrocannabinol (THC) (27 mg/ml):cannabidiol (CBD) (25 mg/ml) as extract of Cannabis sativa L., with peppermint oil, 0.05% (v/v), in ethanol:propylene glycol (50:50) excipient. Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg). The maximum permitted dose of study medication was eight actuations in any three-hour period, and 48 actuations in any 24 hour period.
    Other Name: Sativex
  • Drug: Placebo
    Contained peppermint oil, 0.05% (v/v), quinoline yellow, 0.005% (w/v), sunset yellow, 0.0025% (w/v), in ethanol:propylene glycol (50:50) excipient. Each actuation delivered 100 μl. The maximum permitted dose of study medication was eight actuations in any three-hour period, and 48 actuations in any 24 hour period.
Study Arms  ICMJE
  • Experimental: GW-1000-02
    Active treatment.
    Intervention: Drug: GW-1000-02
  • Placebo Comparator: Placebo
    Placebo control.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 28, 2012)
116
Original Actual Enrollment  ICMJE
 (submitted: May 23, 2012)
137
Actual Study Completion Date  ICMJE January 2005
Actual Primary Completion Date January 2005   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Gave informed consent for participation in the study.
  • Male or Female, aged 18 years or above.
  • Diagnosis of non-acute spinal cord injury, with central neuropathic pain not wholly relieved by current therapy.
  • Central neuropathic pain with a mean severity Numerical Rating Scale score at least four during last seven days of the baseline period.
  • Relatively stable neurology during the preceding six months.
  • Stable medication regimen during the preceding four weeks.
  • Agreement, if female and of child bearing potential or if male with a partner of child bearing potential, to ensure that effective contraception was used during the study and for three months thereafter.
  • Had not used cannabinoids for at least the preceding seven days and willing to abstain from any use of cannabinoids during the study.
  • Clinically acceptable laboratory results at Visit 2.
  • Ability (in the investigator's opinion) and willingness to comply with all study requirements.
  • Agreement for the UK Home Office, their general practitioner, and their consultant if appropriate, to be notified of their participation in the study.

Exclusion Criteria:

  • History of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
  • History of alcohol or substance abuse.
  • Severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias (other than well controlled atrial fibrillation), poorly controlled hypertension or severe heart failure.
  • History of autonomic dysreflexia.
  • History of epilepsy.
  • If female, were pregnant or lactating, or were planning a pregnancy to occur during the course of the study.
  • Significant renal or hepatic impairment.
  • Elective surgery or other procedures requiring general anaesthesia scheduled to occur during the study.
  • Terminal illness or were considered inappropriate for placebo medication.
  • Any other significant disease or disorder which, in the opinion of the investigator, may have either put the subject at risk because of participation in the study, or may influenced the result of the study, or the subject's ability to participate in the study.
  • Regular levodopa therapy within the seven days leading to study entry.
  • If male, were receiving and were unwilling to stop sildenafil for the duration of the study.
  • Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medications.
  • Known or suspected adverse reaction to cannabinoids.
  • Intention to travel internationally during the study.
  • Intention to donate blood during the study.
  • Participation in another research study in the 12 weeks leading to study entry.
  • Previous randomisation into this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01606202
Other Study ID Numbers  ICMJE GWSC0101
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GW Pharmaceuticals Ltd.
Study Sponsor  ICMJE GW Pharmaceuticals Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jonathan Berman, BCh FRCA The Royal National Orthopaedic Hospital
PRS Account GW Pharmaceuticals Ltd.
Verification Date August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP