Multiple Sclerosis, Pain, Spasticity
Conditions
Brief summary
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
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.
Interventions
DRUGGW-1000-02
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.
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events as a Measure of Subject Safety. | Up to 1051 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Parent Study Baseline in Central Neuropathic Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment. | 0 - 52 weeks. | 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. |
| Change From Parent Study Baseline in Neuropathic Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment in Multiple Sclerosis Subjects. | 0 - 52 weeks. | 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. |
| Change From Parent Study Baseline in Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment. | 0 - 52 weeks. | 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. |
| Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Neuropathic Pain Due to Multiple Sclerosis. | Up to 1051 days | 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. |
| Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Neuropathic Pain Due to Multiple Sclerosis. | Up to 1051 days | 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. |
| Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Central Neuropathic Pain. | Up to 1051 days | 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. |
| Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Central Neuropathic Pain. | Up to 1051days | 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. |
| Change From Parent Study Baseline in Spasticity 0-10 Numerical Rating Scale Score After 52 Weeks of Treatment. | 0 - 52 weeks | 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. |
| Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Pain. | Up to 1051 days | 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. |
| Subject Assessment of Benefit at the Last Study Visit in All Multiple Sclerosis Subjects. | Up to 1051 days | 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. |
| Investigator Assessment of Benefit at the Last Study Visit in All Multiple Sclerosis Subjects. | Up to 1051 days. | 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. |
| Investigator Global Assessment at the Last Study Visit in Subjects With Neuropathic Pain Due to Multiple Sclerosis. | Up to 1051 days | 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. |
| Investigator Global Assessment at the Last Study Visit in Subjects With Central Neuropathic Pain. | Up to 1051 days. | 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. |
| Investigator Global Assessment at the Last Study Visit in Subjects With Pain. | Up to 1051 days. | 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. |
| Investigator Global Assessment at the Last Study Visit in Subjects With Multiple Sclerosis. | Up to 1051 days. | 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. |
| Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Pain. | Up to 1051 | 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. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GW-1000-02 Active treatment | 507 |
| Total | 507 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 85 |
| Overall Study | Death | 1 |
| Overall Study | Decreased/no pain | 4 |
| Overall Study | Increased bilirubin | 1 |
| Overall Study | Issues with driving | 4 |
| Overall Study | Lack of Efficacy | 56 |
| Overall Study | Lost to Follow-up | 15 |
| Overall Study | multiple sclerosis less stable | 1 |
| Overall Study | Not enough improvement | 4 |
| Overall Study | Patient leaving country | 1 |
| Overall Study | Patient moving | 1 |
| Overall Study | Patient non-compliance | 9 |
| Overall Study | Personal reasons | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Spray causes nausea | 1 |
| Overall Study | Unable to collect consistent data | 1 |
| Overall Study | Unable to tolerate study med. taste | 1 |
| Overall Study | Wanted to try another treatment | 1 |
| Overall Study | Withdrawal by Subject | 74 |
Baseline characteristics
| Characteristic | GW-1000-02 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 49 Participants |
| Age, Categorical Between 18 and 65 years | 458 Participants |
| Age, Continuous | 50 years STANDARD_DEVIATION 12.3 |
| Region of Enrollment United Kingdom | 507 participants |
| Sex: Female, Male Female | 288 Participants |
| Sex: Female, Male Male | 219 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 477 / 507 |
| serious Total, serious adverse events | 74 / 507 |
Outcome results
Primary
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.
Time frame: Up to 1051 days
Population: All subjects who took part in the extension study were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Incidence of Adverse Events as a Measure of Subject Safety. | 477 participants |
Secondary
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.
Time frame: 0 - 52 weeks.
Population: All subjects who entered the study from a central neuropathic pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GW-1000-02 | Change From Parent Study Baseline in Central Neuropathic Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment. | -2.96 units on a scale | Standard Deviation 2.03 |
Secondary
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.
Time frame: 0 - 52 weeks.
Population: All subjects who entered the study from a neuropathic pain in multiple sclerosis parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GW-1000-02 | Change From Parent Study Baseline in Neuropathic Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment in Multiple Sclerosis Subjects. | -3.11 units on a scale | Standard Deviation 1.9 |
Secondary
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.
Time frame: 0 - 52 weeks.
Population: All subjects who entered the study from a pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GW-1000-02 | Change From Parent Study Baseline in Pain 0-10 Numerical Rating Scale Score at 52 Weeks of Treatment. | -2.57 units on a scale | Standard Deviation 2.02 |
Secondary
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.
Time frame: 0 - 52 weeks
Population: All subjects who entered the study from a parent randomised controlled trial (RCT) investigating the efficacy of GW-1000-02 in the treatment of spasticity associated with multiple sclerosis, and who received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GW-1000-02 | Change From Parent Study Baseline in Spasticity 0-10 Numerical Rating Scale Score After 52 Weeks of Treatment. | -1.83 units on a scale | Standard Deviation 2.41 |
Secondary
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.
Time frame: Up to 1051 days.
Population: All subjects who entered the study from a multiple sclerosis parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Investigator Assessment of Benefit at the Last Study Visit in All Multiple Sclerosis Subjects. | 200 participants |
Secondary
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.
Time frame: Up to 1051days
Population: All subjects who entered the study from a neuropathic pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Central Neuropathic Pain. | 111 participants |
Secondary
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.
Time frame: Up to 1051 days
Population: All multiple sclerosis subjects who entered the study from a neuropathic pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Neuropathic Pain Due to Multiple Sclerosis. | 76 participants |
Secondary
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.
Time frame: Up to 1051 days
Population: All subjects who entered the study from a pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Investigator Assessment of Benefit at the Last Study Visit in Those Experiencing Pain. | 190 participants |
Secondary
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.
Time frame: Up to 1051 days.
Population: All subjects who entered the study from a central neuropathic pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Investigator Global Assessment at the Last Study Visit in Subjects With Central Neuropathic Pain. | 83 participants |
Secondary
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.
Time frame: Up to 1051 days.
Population: All subjects who entered the study from a multiple sclerosis parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Investigator Global Assessment at the Last Study Visit in Subjects With Multiple Sclerosis. | 87 participants |
Secondary
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.
Time frame: Up to 1051 days
Population: All subjects who entered the study from a parent RCT investigation neuropathic pain due to multiple sclerosis, and who received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Investigator Global Assessment at the Last Study Visit in Subjects With Neuropathic Pain Due to Multiple Sclerosis. | 30 participants |
Secondary
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.
Time frame: Up to 1051 days.
Population: All subjects who entered the study from a pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Investigator Global Assessment at the Last Study Visit in Subjects With Pain. | 122 participants |
Secondary
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.
Time frame: Up to 1051 days
Population: All subjects who entered the study from a multiple sclerosis parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Subject Assessment of Benefit at the Last Study Visit in All Multiple Sclerosis Subjects. | 199 participants |
Secondary
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.
Time frame: Up to 1051 days
Population: All subjects who entered the study from a neuropathic pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Central Neuropathic Pain. | 112 participants |
Secondary
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.
Time frame: Up to 1051 days
Population: All multiple sclerosis subjects who entered the study from a neuropathic pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Neuropathic Pain Due to Multiple Sclerosis. | 75 participants |
Secondary
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.
Time frame: Up to 1051
Population: All subjects who entered the study from a pain parent RCT and received at least one actuation of study medication were included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Subject Assessment of Benefit at the Last Study Visit in Those Experiencing Pain. | 193 participants |