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The purpose of this study is to evaluate the maintenance of effect after long-term treatment with Sativex® in subjects with symptoms of spasticity due to Multiple Sclerosis (MS) who have been receiving long-term benefit from treatment with Sativex®.
Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2023-05-06
What this record can show
Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.
Registry facts
This five week (one week baseline and four weeks randomised treatment period), multi-centre, placebo controlled, parallel group, randomized withdrawal study will evaluate the maintenance of effect after long-term treatment with Sativex® in subjects with symptoms of spasticity due to MS who have been receiving long-term benefit from treatment with Sativex®. Subjects will be selected from the Supply of Unlicensed Sativex® (SUS) or named patient supply programmes and must have been receiving Sativex® for at least 12 weeks prior to study entry. Following informed consent and screening, eligible subjects will enter the study (Visit 1, Day 1) and commence a seven day open label baseline period, before returning for a randomisation visit (Visit 2, Day 7), at which point they are randomised to receive either Sativex® or placebo (randomised withdrawal period). Subjects will return to the centre for an end of study visit at week five (Visit 3, Day 35) or earlier if they withdraw from treatment. Spasticity and sleep disruption review and dosing diaries will be completed each day from the start of the baseline period until completion or withdrawal.
Linked local records
Local links use governed condition terms or exact source-reported intervention names. They are navigation candidates, not efficacy claims.
Interventions
containing delta-9-tetrahydrocannabinol (THC)(27 mg/ml):cannabidiol (CBD)(25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Dose: 100 µl oromucosal spray, as required for symptom relief
GW-1000-02Contains no active drug and is delivered in 100 microlitre actuations by a pump action oromucosal spray
Source-reported results
Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.
The time to treatment failure was calculated as the number of days from the first day of treatment up to the day of treatment failure. The day of treatment failure was the earliest of:the day of premature cessation of study medication;the first day of the longest period, ending on the last day of treatment, where the mean spasticity NRS had increased by at least 20% and at least 1 unit from the treatment baseline; the day of a clinically relevant increase in anti-spasticity or disease modifying medication. The number of subjects who failed treatment were calculated.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 18 | 8 | - |
| Placebo | 18 | 17 | - |
Spasticity NRS was completed daily by answering the following question: "On a scale of '0 to 10' please indicate the average level of your spasticity over the last 24 hours" with the anchors: 0 = 'no spasticity' and 10 = 'worst possible spasticity'. The change in mean spasticity severity NRS from baseline to end of study (last seven days)was calculated. A negative change from baseline indicates an improvement in spasticity.
Eligibility
primary outcomes
Time frame: Week 1- Week 5
The time to treatment failure was calculated as the number of days from the first day of treatment up to the day of treatment failure. The day of treatment failure was the earliest of:the day of premature cessation of study medication;the first day of the longest period, ending on the last day of treatment, where the mean spasticity NRS had increased by at least 20% and at least 1 unit from the treatment baseline; the day of a clinically relevant increase in anti-spasticity or disease modifying medication. The number of subjects who failed treatment were calculated.
secondary outcomes
Time frame: Baseline (Week 1) to Week 5
Spasticity NRS was completed daily by answering the following question: "On a scale of '0 to 10' please indicate the average level of your spasticity over the last 24 hours" with the anchors: 0 = 'no spasticity' and 10 = 'worst possible spasticity'. The change in mean spasticity severity NRS from baseline to end of study (last seven days)was calculated. A negative change from baseline indicates an improvement in spasticity.
Time frame: Day 7 to Day 28
The Modified Ashworth Scale was completed at baseline and at the end of treatment at approximately the same time of day. All 20 muscle groups were assessed for spasticity (using a 0=no increase in muscle tone to 4 scale=affected part rigid in flexion or extensions), to result in a total score out of 80. The higher the score the worse the spasticity is. The change from baseline to end of study was assessed. The higher the score the better
Time frame: Week 2 and Week 5
The Motricity Index involves assessing three movements in both the arms and the legs. In the arm the three movements are; pinch grip, elbow flexion and shoulder abduction and the three leg movements are, ankle dorsiflexion, knee extension and hip flexion. The total arm/leg score is then the addition of the score for the three arm/leg movements. One point is then added to each limb score so that the maximum score is 100 points. The higher the score the better the limb movement.
Time frame: Week 2 and Week 5
The time taken to travel 10 metres.
Time frame: Week 1- Week 5
Subjects will be asked: "On a scale of 0-10 please indicate how your spasticity disrupted your sleep last night" with the anchors 0 = 'did not disrupt sleep', 10 = 'completely disrupted (unable to sleep at all)'.
Time frame: Day 35
At baseline subjects will write a brief description of their spasticity caused by MS and how it affects them emotionally, physically and their ability to function with day to day activities. This will be used to aid their memory before they answer the following question which is rated on a seven-point scale. "Please assess the change in your spasticity due to MS since immediately before receiving the first course of study treatment (Baseline) using the scale below" The markers are: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better.
Publications
No exact PMID-linked public article is currently readable locally.
Population: It is important to note that 17 of the placebo subjects withdrew from the study early. All subjects were accounted for in this analysis by use of a last-observation-carried-forward approach.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 18 | 1.11 | 1.92 |
| Placebo | 18 | 1.10 | 1.91 |
The Modified Ashworth Scale was completed at baseline and at the end of treatment at approximately the same time of day. All 20 muscle groups were assessed for spasticity (using a 0=no increase in muscle tone to 4 scale=affected part rigid in flexion or extensions), to result in a total score out of 80. The higher the score the worse the spasticity is. The change from baseline to end of study was assessed. The higher the score the better
Population: ITT. The reason for not including some of the data in this analysis is that a number of the subjects who withdrew early from the study restarted their own Sativex before the assessment was done.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 17 | 21.5 | 12.73 |
| Placebo | 8 | 22.9 | 17.11 |
The Motricity Index involves assessing three movements in both the arms and the legs. In the arm the three movements are; pinch grip, elbow flexion and shoulder abduction and the three leg movements are, ankle dorsiflexion, knee extension and hip flexion. The total arm/leg score is then the addition of the score for the three arm/leg movements. One point is then added to each limb score so that the maximum score is 100 points. The higher the score the better the limb movement.
Population: ITT. The reason for not including some of the data in this analysis is that a number of the subjects who withdrew early from the study restarted their own Sativex before the assessment was done.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 16 | 72.4 | 6.26 |
| Placebo | 7 | 92.5 | 0 |
| Sativex | 16 | 43.6 | 31.40 |
| Placebo | 7 | 47.0 | 21.38 |
The time taken to travel 10 metres.
Population: ITT. Only 4 placebo subjects were included in the analysis and 11 of the Sativex subjects. The reason for not including some of the data in this analysis is that a number of the subjects who withdrew early from the study restarted their own Sativex before the assessment was done.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 11 | 47.3 | 50.29 |
| Placebo | 4 | 18.3 | 4.5 |
Subjects will be asked: "On a scale of 0-10 please indicate how your spasticity disrupted your sleep last night" with the anchors 0 = 'did not disrupt sleep', 10 = 'completely disrupted (unable to sleep at all)'.
Population: It is important to note that 16 of the placebo subjects withdrew from the study early. All subjects were accounted for in this analysis by use of a last-observation-carried-forward approach.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 18 | 2.90 | 2.48 |
| Placebo | 18 | 3.36 | 2.18 |
At baseline subjects will write a brief description of their spasticity caused by MS and how it affects them emotionally, physically and their ability to function with day to day activities. This will be used to aid their memory before they answer the following question which is rated on a seven-point scale. "Please assess the change in your spasticity due to MS since immediately before receiving the first course of study treatment (Baseline) using the scale below" The markers are: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 18 | 0 | - |
| Placebo | 18 | 0 | - |
| Sativex | 18 | 0 | - |
| Placebo | 18 | 0 | - |
| Sativex | 18 | 0 | - |
| Placebo | 18 | 0 | - |
| Sativex | 18 | 6 | - |
| Placebo | 18 | 1 | - |
| Sativex | 18 | 6 | - |
| Placebo | 18 | 5 | - |
| Sativex | 18 | 5 | - |
| Placebo | 18 | 9 | - |
| Sativex | 18 | 1 | - |
| Placebo | 18 | 3 | - |
The main carer will be asked to assess the change in the subject's condition at the end of the study (completion or withdrawal). It consists of 2 question which is rated on a seven-point scale: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better. The carer will be asked since visit 2 (baseline): "How has the subject's general functional abilities changed?" "How has the subject's ease of transfer?" Not all subjects had carers; a total of 18 subjects from each treatment, of which 10 from Sativex and 14 from placebo completed it.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 10 | 0 | - |
| Placebo | 14 | 0 | - |
| Sativex | 10 | 0 | - |
| Placebo | 14 | 0 | - |
| Sativex | 10 | 0 | - |
| Placebo | 14 | 0 | - |
| Sativex | 10 | 3 | - |
| Placebo | 14 | 0 | - |
| Sativex | 10 | 5 | - |
| Placebo | 14 | 3 | - |
| Sativex | 10 | 2 | - |
| Placebo | 14 | 9 | - |
| Sativex | 10 | 0 | - |
| Placebo | 14 | 2 | - |
The main carer will be asked to assess the change in the subject's condition at the end of the study (completion or withdrawal). It consists of 2 question which is rated on a seven-point scale: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better. The carer will be asked since visit 2 (baseline): "How has the subject's general functional abilities changed?" "How has the subject's ease of transfer?" Not all subjects had carers; a total of 18 subjects from each treatment, of which 10 from Sativex and 14 from placebo completed it.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 10 | 0 | - |
| Placebo | 14 | 0 | - |
| Sativex | 10 | 0 | - |
| Placebo | 14 | 0 | - |
| Sativex | 10 | 0 | - |
| Placebo | 14 | 0 | - |
| Sativex | 10 | 3 | - |
| Placebo | 14 | 2 | - |
| Sativex | 10 | 5 | - |
| Placebo | 14 | 5 | - |
| Sativex | 10 | 2 | - |
| Placebo | 14 | 6 | - |
| Sativex | 10 | 0 | - |
| Placebo | 14 | 1 | - |
| Milestone | Sativex | Placebo |
|---|---|---|
| STARTED | 18 | 18 |
| COMPLETED | 15 | 2 |
| NOT COMPLETED | 3 | 16 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Diarrhoea | Gastrointestinal disorders | Sativex: 2 / 18 · Placebo: 1 / 18 |
| Mouth Ulceration | Gastrointestinal disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Stomach Discomfort | Gastrointestinal disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Vomitting | Gastrointestinal disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Nausea | Gastrointestinal disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Fatigue | General disorders | Sativex: 2 / 18 · Placebo: 0 / 18 |
| Pain | General disorders | Sativex: 2 / 18 · Placebo: 7 / 18 |
| Application site pain | General disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Asthenia | General disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Gait disturbance | General disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Urinary tract infection | Infections and infestations | Sativex: 3 / 18 · Placebo: 0 / 18 |
| Cystitis | Infections and infestations | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Lower respiratory tract infection | Infections and infestations | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Nasopharyngitis | Infections and infestations | Sativex: 1 / 18 · Placebo: 1 / 18 |
| Oral Herpes | Infections and infestations | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Contusion | Injury, poisoning and procedural complications | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Gamma-glutamyltransferase increase | Investigations | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Anorexia | Metabolism and nutrition disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Muscle spasms | Musculoskeletal and connective tissue disorders | Sativex: 3 / 18 · Placebo: 2 / 18 |
| Back pain | Musculoskeletal and connective tissue disorders | Sativex: 3 / 18 · Placebo: 1 / 18 |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | Sativex: 2 / 18 · Placebo: 1 / 18 |
| Joint stiffness | Musculoskeletal and connective tissue disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Arthralgia | Musculoskeletal and connective tissue disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Musculoskeletal Discomfort | Musculoskeletal and connective tissue disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Neck pain | Musculoskeletal and connective tissue disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Sensation of heaviness | Musculoskeletal and connective tissue disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Muscle spasticity | Nervous system disorders | Sativex: 2 / 18 · Placebo: 3 / 18 |
| Dizziness | Nervous system disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Somnolence | Nervous system disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Tremor | Nervous system disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Multiple Sclerosis | Nervous system disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Hyperaesthesia | Nervous system disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Paraesthesia | Nervous system disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Trigeminal neuralgia | Nervous system disorders | Sativex: 0 / 18 · Placebo: 2 / 18 |
| Depressed mood | Psychiatric disorders | Sativex: 0 / 18 · Placebo: 2 / 18 |
| Insomnia | Psychiatric disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Sleep disorder | Psychiatric disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Haematuria | Renal and urinary disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Hypertonic Bladder | Renal and urinary disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Cough | Respiratory, thoracic and mediastinal disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Rash | Skin and subcutaneous tissue disorders | Sativex: 1 / 18 · Placebo: 0 / 18 |
| Skin tightness | Skin and subcutaneous tissue disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Hot flush | Vascular disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
| Hypertension | Vascular disorders | Sativex: 0 / 18 · Placebo: 1 / 18 |
Time frame: Day 35
The main carer will be asked to assess the change in the subject's condition at the end of the study (completion or withdrawal). It consists of 2 question which is rated on a seven-point scale: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better. The carer will be asked since visit 2 (baseline): "How has the subject's general functional abilities changed?" "How has the subject's ease of transfer?" Not all subjects had carers; a total of 18 subjects from each treatment, of which 10 from Sativex and 14 from placebo completed it.
Time frame: Day 35
The main carer will be asked to assess the change in the subject's condition at the end of the study (completion or withdrawal). It consists of 2 question which is rated on a seven-point scale: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better. The carer will be asked since visit 2 (baseline): "How has the subject's general functional abilities changed?" "How has the subject's ease of transfer?" Not all subjects had carers; a total of 18 subjects from each treatment, of which 10 from Sativex and 14 from placebo completed it.