A Study of the Long-term Safety of Sativex Use

Study Overview
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Brief Summary
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Subjects who had previously received GW-1000-02 in a GW study who opted to continue using it in the long-term were monitored for ongoing tolerability and evidence of clinical benefit.

Detailed Description
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Subjects who had previously participated in a placebo controlled GW clinical study were screened and if eligible began dosing with GW-1000-02. Subjects were reviewed for tolerability and evidence of clinical benefit at weeks two and four and then every eight weeks. Subjects self-titrated to symptom resolution or maximum tolerated/allowable dose of 130 mg THC and 120 mg CBD.

Official Title
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A Long-term, Open Label, Safety and Tolerability Study of Cannabis Based Medicine Extract in Patients Who Have Participated in a GW Clinical Study Using Cannabis Based Medicine.

Conditions
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Multiple Sclerosis, Spasticity, Pain

Intervention / Treatment
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* Drug: GW-1000-02


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to give informed consent. Male or female aged 18 years or above. Diagnosed with a condition categorised as one of the following: multiple sclerosis, spinal cord conditions, peripheral nerve injury or central nervous system damage associated with vascular, traumatic, infective, genetic or metabolic disease and whose symptom(s) were not wholly relieved by currently available therapy, prior to the previous study of GW-1000-02 or placebo. Had participated in a GW clinical study using GW-1000-02 within the previous month. Had shown tolerability to the study medication during the previous GW study. Was expected, by the investigator, to gain clinical benefit from receiving long-term GW-1000-02. Were willing, if female and of child bearing potential or male subjects 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 (cannabis, Marinol or Nabilone) for at least seven days before Visit 1 (the exception being GW-1000-02 given as study medication) and were willing to abstain from any use of cannabis during the study. Recent (within seven days) haematology and blood chemistry that was normal or considered clinically acceptable in view of the subjects underlying condition. Able (in the investigators opinion) and willing to comply with all study requirements. Willing for the Home Office to be notified of his or her participation in the study. Willing to allow his or her general practitioner and consultant, if appropriate, to be notified of participation in the study. Exclusion Criteria: History of serious psychiatric illness, including schizophrenia, other psychotic illness or severe personality disorder other than depression associated with the underlying condition. Known or strongly suspected of alcohol or substance abuse or considered by the investigator to have been at risk 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 epilepsy or convulsions. Significant renal or hepatic impairment. Terminally ill. 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 have influenced the result of the study, or the subject's ability to participate in the study. Female subjects who were pregnant, lactating or planning pregnancy during the course of the study. Regular levodopa (Sinemet, Sinemet Plus, Levodopa, L-dopa, Madopar, Benserazide) therapy within seven days of study entry. Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medication. Known or suspected adverse reaction to cannabinoids. Donation of blood during the study. Previous participation in this 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GW-1000-02<br>Active treatment | Drug: GW-1000-02<br>* Contained delta-9-tetrahydrocannabinol (THC) (27 mg/ml) and 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 100 μl actuation of the pump action spray delivered 2.7 mg THC and 2.5 mg CBD. A maximum daily exposure of 130 mg THC was specified by the UK regulatory authority authorisation.<br>* Other names: Sativex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events as a Measure of Subject Safety. | Following data entry, all adverse events were medically encoded using the Medical Dictionary for Regulatory Activities (MedDRA) 6.0. All subjects who experienced an adverse event during the treatment period is presented. | Up to 1051 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Parent Study Baseline in Spasticity 0-10 Numerical Rating Scale Score After 52 Weeks of Treatment. | Subjects were asked to rate the severity of their primary symptom each week in the diary using an 11-point Numerical Rating Scale, where zero = best possible and 10 = worst possible. A negative value indicates an improvement in score from baseline. | 0 - 52 weeks | 
| Change From Parent Study Baseline in Central Neuropathic Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment. | Subjects were asked to rate the severity of their primary symptom each week in the diary using an 11-point Numerical Rating Scale, where zero = best possible and 10 = worst possible. A negative value indicates an improvement in score from baseline. | 0 - 52 weeks. | 
| Change From Parent Study Baseline in Neuropathic Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment in Multiple Sclerosis Subjects. | Subjects were asked to rate the severity of their primary symptom each week in the diary using an 11-point Numerical Rating Scale, where zero = best possible and 10 = worst possible. A negative value indicates an improvement in score from baseline. | 0 - 52 weeks. | 
| Change From Parent Study Baseline in Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment. | Subjects were asked to rate the severity of their primary symptom each week in the diary using an 11-point Numerical Rating Scale, where zero = best possible and 10 = worst possible. A negative value indicates an improvement in score from baseline. | 0 - 52 weeks. | 
| Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Neuropathic Pain Due to Multiple Sclerosis. | Assessment of benefit achieved at study completion/withdrawal was evaluated by the subject, and the number of subjects who perceived a benefit from treatment is presented. | Up to 1051 days | 
| Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Neuropathic Pain Due to Multiple Sclerosis. | Assessment of benefit achieved at study completion/withdrawal was evaluated by the investigator, and the number of subjects that investigators considered to have experienced a benefit from the treatment is presented. | Up to 1051 days | 
| Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Central Neuropathic Pain. | Assessment of benefit achieved at study completion/withdrawal was evaluated by the subject, and the number of subjects who perceived a benefit from treatment is presented. | Up to 1051 days | 
| Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Central Neuropathic Pain. | Assessment of benefit achieved at study completion/withdrawal was evaluated by the investigator, and the number of subjects that investigators considered to have experienced a benefit from the treatment is presented. | Up to 1051days | 
| Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Pain. | Assessment of benefit achieved at study completion/withdrawal was evaluated by the subject, and the number of subjects who perceived a benefit from treatment is presented. | Up to 1051 | 
| Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Pain. | Assessment of benefit achieved at study completion/withdrawal was evaluated by the investigator, and the number of subjects that investigators considered to have experienced a benefit from the treatment is presented. | Up to 1051 days | 
| Subject Assessment of Benefit at the Last Study Visit in All Multiple Sclerosis Subjects. | Assessment of benefit achieved at study completion/withdrawal was evaluated by the subject, and the number of subjects who perceived a benefit from treatment is presented. | Up to 1051 days | 
| Investigator Assessment of Benefit at the Last Study Visit in All Multiple Sclerosis Subjects. | Assessment of benefit achieved at study completion/withdrawal was evaluated by the investigator, and the number of subjects that investigators considered to have experienced a benefit from the treatment is presented. | Up to 1051 days. | 
| Investigator Global Assessment at the Last Study Visit in Subjects With Neuropathic Pain Due to Multiple Sclerosis. | Investigators rated the global severity of the subject's underlying primary condition, e.g. their MS or spinal cord injury, since the previous visit using a five point scale of much worse, worse, no change, better, much better. The number of subjects rated by the investigator as better or much better at the last study visit is presented. | Up to 1051 days | 
| Investigator Global Assessment at the Last Study Visit in Subjects With Central Neuropathic Pain. | Investigators rated the global severity of the subject's underlying primary condition, e.g. their MS or spinal cord injury, since the previous visit using a five point scale of much worse, worse, no change, better, much better. The number of subjects rated by the investigator as better or much better at the last study visit is presented. | Up to 1051 days. | 
| Investigator Global Assessment at the Last Study Visit in Subjects With Pain. | Investigators rated the global severity of the subject's underlying primary condition, e.g. their MS or spinal cord injury, since the previous visit using a five point scale of much worse, worse, no change, better, much better. The number of subjects rated by the investigator as better or much better at the last study visit is presented. | Up to 1051 days. | 
| Investigator Global Assessment at the Last Study Visit in Subjects With Multiple Sclerosis. | Investigators rated the global severity of the subject's underlying primary condition, e.g. their MS or spinal cord injury, since the previous visit using a five point scale of much worse, worse, no change, better, much better. The number of subjects rated by the investigator as better or much better at the last study visit is presented. | Up to 1051 days. |