Multiple Sclerosis, Spasticity
Conditions
Brief summary
An extension study to evaluate the long-term safety, tolerability and efficacy of GW-1000-02 treatment in multiple sclerosis.
Detailed description
Patients who participated in the placebo controlled phase of this study and opted to continue receiving open label GW-1000-02 entered the follow-on extension of the study and completed symptom assessments to determine whether they were continuing to receive clinical benefit from GW-1000-02.
Interventions
DRUGGW-1000-02
Contained THC and CBD as extract of Cannabis sativa L. Each 100 μl actuation delivered a dose containing 2.7 mg THC and 2.5mg CBD. The maximum permitted dose was eight actuations (22 mg THC and 20 mg CBD) in any three hour period, and 48 actuations (130 mg THC and 120 mg CBD) in any 24 hour period.
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
* Aged at least 18 years. * Multiple Sclerosis of any type. * Stable Multiple Sclerosis symptomatology during the four weeks before study entry. * Symptoms of the required severity (\>50 mm on a 100 mm Visual Analogue Scale severity scale) in least one of the specified impairment categories; spasticity, muscle spasms, disturbed bladder control, neuropathic pain, limb tremor. * A stable medication regime during the four weeks before study entry. * Willing to abstain from cannabis or cannabinoids for at least seven days before study entry, and during the study. * Agreed either to use effective contraception during the study and for three months thereafter, or had been surgically sterilised or, if female, were post-menopausal. * Clinically acceptable laboratory results for pre-study screening. * Willing and able to undertake and comply with all study requirements. * Willing and able to read, consider and understand the subject information and consent form and give written informed consent. Subjects unable to read or to sign the document procedures were treated as detailed in the Declaration of Helsinki. * Willing for their general practitioner, and consultant if appropriate, to be informed of study participation. * Willing for their name to be notified to Home Office for participation in the study.
Exclusion criteria
* Known or strongly suspected to be abusing drugs, including alcohol. * Not prepared to abstain from cannabis or cannabinoids during the study. * Current or past addiction to cannabis. * Known or suspected to have had an adverse reaction to cannabinoids causing psychosis or other severe psychiatric illness. * History of any type of schizophrenia, any other psychotic illness, or other significant psychiatric illness or personality disorder other than depression associated with chronic illness. * Received any drug containing levodopa (Sinemet®, Sinemet plus®, Levodopa®, L-dopa®, Madopar®, Benserazide®). * Serious cardiovascular disorder including angina, uncontrolled hypertension, or an uncontrolled symptomatic cardiac arrhythmia. * Significant renal or hepatic impairment as shown in medical history or indicated by laboratory results. * History of epilepsy. * Terminal illness or other condition in which placebo medication would be inappropriate. * Pregnant, lactating or at risk of pregnancy. * Participated in any other clinical research study during the 12 weeks before study entry. * Planned hospital admission between study entry and Visit 6. * Planned travel outside the UK between study entry and Visit 6.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events as a Measure of Patient Safety | up to1206 days | The number of patients who experienced an adverse event during the course of this extension study is presented |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of Sprays of Study Medication Taken During the Last 6 Days of Treatment | up to 1206 days | A categorical summary was produced of the mean number of sprays per day during the last six days of treatment, and the mean number of sprays was rounded to the nearest whole number for categorisation. |
| Change From Baseline in Mean Intoxication 100 mm Visual Analogue Scale Scores at Week 18. | 18 weeks | Intoxication levels were recorded on a Visual Analogue Scale, where 0 equals 'no intoxication' and 10 equals 'extreme intoxication'. A decrease in score indicates an improvement in intoxication levels. |
| Investigator Assessed Global Severity Score at Week 18 | week 18 | The investigator rated the global severity of the subject's primary condition since entry into the study using a five-point verbal rating scale-5: 1=much worse, 2=worse, 3=no change, 4=better, 5=much better. The number of patients which were considered better or much better (scores 4 and 5) at week 18 of the study better is presented. |
| Change From Baseline in the Mean Pain 100 mm Visual Analogue Scale Score at Week 18 | week 18 | A clinical assessment of pain was made at each study visit using a 100 mm Visual Analogue Scale, where 0 = no pain and 100 = worst possible pain. A decrease in score indicates an improvement. |
| Change From Baseline in the Mean Spasticity 100 mm Visual Analogue Scale Score at Week 18 | week 18 | A clinical assessment of spasticity was made at each study visit using a 100 mm Visual Analogue Scale, where 0 = no spasticity and 100 = worst possible spasticity. A decrease in score indicates an improvement. |
| Change From Baseline in the Mean Tremor 100 mm Visual Analogue Scale Score at Week 18 | week 18 | A clinical assessment of tremor was made at each study visit using a 100 mm Visual Analogue Scale, where 0 = no tremor and 100 = worst possible tremor. A decrease in score indicates an improvement. |
| Change From Baseline in the Mean Bladder Problems 100 mm Visual Analogue Scale Score at Week 18 | 18 weeks | A clinical assessment of bladder problems was made at each study visit using a 100 mm Visual Analogue Scale, where 0 = no bladder problems and 100 = worst possible bladder problems. A decrease in score indicates an improvement. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GW-1000-02 Active treatment | 137 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 18 |
| Overall Study | Cannabis affecting job | 1 |
| Overall Study | Death | 1 |
| Overall Study | Felt more alter without study medication | 1 |
| Overall Study | Lack of Efficacy | 26 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Moved out of area | 6 |
| Overall Study | Symptom control without study medication | 2 |
| Overall Study | Unable to make journey | 1 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | GW-1000-02 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 127 Participants |
| Age, Continuous | 50.69 years STANDARD_DEVIATION 9.531 |
| Region of Enrollment United Kingdom | 137 participants |
| Sex: Female, Male Female | 83 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 127 / 137 |
| serious Total, serious adverse events | 23 / 137 |
Outcome results
Primary
Incidence of Adverse Events as a Measure of Patient Safety
The number of patients who experienced an adverse event during the course of this extension study is presented
Time frame: up to1206 days
Population: All subjects who took at least one dose of study medication after the end of the Part B open-label phase of the acute study, and yielded on-treatment efficacy data was classed as the efficacy and safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Incidence of Adverse Events as a Measure of Patient Safety | 126 participants |
Secondary
Change From Baseline in Mean Intoxication 100 mm Visual Analogue Scale Scores at Week 18.
Intoxication levels were recorded on a Visual Analogue Scale, where 0 equals 'no intoxication' and 10 equals 'extreme intoxication'. A decrease in score indicates an improvement in intoxication levels.
Time frame: 18 weeks
Population: All subjects who took at least one dose of study medication after the end of the Part B open-label phase of the acute study, and yielded on-treatment efficacy data was classed as the efficacy and safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GW-1000-02 | Change From Baseline in Mean Intoxication 100 mm Visual Analogue Scale Scores at Week 18. | 2.65 units on a scale | Standard Deviation 14.15 |
Secondary
Change From Baseline in the Mean Bladder Problems 100 mm Visual Analogue Scale Score at Week 18
A clinical assessment of bladder problems was made at each study visit using a 100 mm Visual Analogue Scale, where 0 = no bladder problems and 100 = worst possible bladder problems. A decrease in score indicates an improvement.
Time frame: 18 weeks
Population: All subjects who took at least one dose of study medication after the end of the Part B open-label phase of the acute study, and yielded on-treatment efficacy data was classed as the efficacy and safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GW-1000-02 | Change From Baseline in the Mean Bladder Problems 100 mm Visual Analogue Scale Score at Week 18 | -33.60 units on a scale | Standard Deviation 25.12 |
Secondary
Change From Baseline in the Mean Pain 100 mm Visual Analogue Scale Score at Week 18
A clinical assessment of pain was made at each study visit using a 100 mm Visual Analogue Scale, where 0 = no pain and 100 = worst possible pain. A decrease in score indicates an improvement.
Time frame: week 18
Population: All subjects who took at least one dose of study medication after the end of the Part B open-label phase of the acute study, and yielded on-treatment efficacy data was classed as the efficacy and safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GW-1000-02 | Change From Baseline in the Mean Pain 100 mm Visual Analogue Scale Score at Week 18 | -31.34 units on a scale | Standard Deviation 27.2 |
Secondary
Change From Baseline in the Mean Spasticity 100 mm Visual Analogue Scale Score at Week 18
A clinical assessment of spasticity was made at each study visit using a 100 mm Visual Analogue Scale, where 0 = no spasticity and 100 = worst possible spasticity. A decrease in score indicates an improvement.
Time frame: week 18
Population: All subjects who took at least one dose of study medication after the end of the Part B open-label phase of the acute study, and yielded on-treatment efficacy data was classed as the efficacy and safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GW-1000-02 | Change From Baseline in the Mean Spasticity 100 mm Visual Analogue Scale Score at Week 18 | -27.81 units on a scale | Standard Deviation 24.46 |
Secondary
Change From Baseline in the Mean Tremor 100 mm Visual Analogue Scale Score at Week 18
A clinical assessment of tremor was made at each study visit using a 100 mm Visual Analogue Scale, where 0 = no tremor and 100 = worst possible tremor. A decrease in score indicates an improvement.
Time frame: week 18
Population: All subjects who took at least one dose of study medication after the end of the Part B open-label phase of the acute study, and yielded on-treatment efficacy data was classed as the efficacy and safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GW-1000-02 | Change From Baseline in the Mean Tremor 100 mm Visual Analogue Scale Score at Week 18 | -26.23 units on a scale | Standard Deviation 23.9 |
Secondary
Investigator Assessed Global Severity Score at Week 18
The investigator rated the global severity of the subject's primary condition since entry into the study using a five-point verbal rating scale-5: 1=much worse, 2=worse, 3=no change, 4=better, 5=much better. The number of patients which were considered better or much better (scores 4 and 5) at week 18 of the study better is presented.
Time frame: week 18
Population: All subjects who took at least one dose of study medication after the end of the Part B open-label phase of the acute study, and yielded on-treatment efficacy data was classed as the efficacy and safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GW-1000-02 | Investigator Assessed Global Severity Score at Week 18 | 92 participants |
Secondary
Mean Number of Sprays of Study Medication Taken During the Last 6 Days of Treatment
A categorical summary was produced of the mean number of sprays per day during the last six days of treatment, and the mean number of sprays was rounded to the nearest whole number for categorisation.
Time frame: up to 1206 days
Population: All subjects who took at least one dose of study medication after the end of the Part B open-label phase of the acute study, and yielded on-treatment efficacy data was classed as the efficacy and safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GW-1000-02 | Mean Number of Sprays of Study Medication Taken During the Last 6 Days of Treatment | 8.09 sprays of study medication | Standard Deviation 7.91 |