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A study to compare the change in cognitive performance and psychological status of patients with spasticity due to Multiple Sclerosis when treated with Sativex or placebo, added to existing anti-spasticity therapy over a period of 48 weeks. Secondary objectives were to evaluate the effect of Sativex on mood and spasticity and to assess the safety and tolerability of Sativex.
Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2023-01-12
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
Eligible patients entered this 50 week multicenter, double-blind, randomised, placebo-controlled, parallel group study which evaluated the effect of Sativex on cognitive performance. At each scheduled clinic visit, patients were assessed for cognitive performance, mood, severity of spasticity, use of investigational medicinal products and number of visits to a healthcare professional. Primary efficacy comparisons were made between scores recorded during baseline and scores recorded at the end of treatment.
Linked local records
Local links use governed condition terms or exact source-reported intervention names. They are navigation candidates, not efficacy claims.
Interventions
Patients self-administered their allocated randomized treatment on an outpatient basis, up to a maximum of 12 sprays to the oral mucosa per day (following an initial titration period).
Nabiximols · GWP42001 · THC/CBD sprayPatients self-administered their allocated randomized treatment on an outpatient basis, up to a maximum of 12 sprays to the oral mucosa per day (following an initial titration period).
Placebo controlSource-reported results
Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.
The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Stimulus presentation rates were adapted for use with multiple sclerosis patients. The PASAT is presented on audio compact disk to control the rate of stimulus presentation. Single digits are presented either every 3 seconds (PASAT 1) or every 2 seconds (PASAT 2), and the patient must add each new digit to the one immediately prior to it. The test score is the sum of the total number of correct sums given (out of 60 possible) in each trial. An increase in score indicates an improvement in condition.
Population: All randomized patients who received at least one dose of study medication and yielded on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 55 | 6.8 | 16.16 |
| Placebo | 52 | 6.8 | 13.49 |
Eligibility
primary outcomes
Time frame: 0-48 weeks
The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Stimulus presentation rates were adapted for use with multiple sclerosis patients. The PASAT is presented on audio compact disk to control the rate of stimulus presentation. Single digits are presented either every 3 seconds (PASAT 1) or every 2 seconds (PASAT 2), and the patient must add each new digit to the one immediately prior to it. The test score is the sum of the total number of correct sums given (out of 60 possible) in each trial. An increase in score indicates an improvement in condition.
secondary outcomes
Time frame: 0-48 weeks
The BDI-II is a multiple choice self-reported inventory that is one of the most widely used instruments for measuring the severity of depression. There are 21 questions or items, each having four possible responses. Each response is assigned a score ranging from zero to three, indicating the severity of the symptom. Items 1 to 13 assess symptoms that are psychological in nature, while items 14 to 21 assess symptoms that are more physical. The sum of all BDI-II item scores indicates the severity of depression. For patients eligible for this study, a score of 21 or over represents depression. The BDI-II can distinguish between different subtypes of depressive disorders, such as major depression and dysthymia. A reduction in score indicates an improvement in condition.
Time frame: 0-48 weeks
Patients were asked the following question, to be rated on a seven-point scale: "Please assess the change in your spasticity since immediately before receiving the first dose of study treatment (Visit 1) using the scale below". The markers were: 'Very much worse', 'Much worse', 'Minimally worse', 'No change', 'Minimally better', 'Much better' or 'Very much better'. The number of patients for each of the markers is presented at the final study visit.
Time frame: 0-48 weeks
Caregivers were asked the following question to be rated on a seven-point scale: "How has the subject's spasticity changed since Visit 1?" The markers were: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better. The number of patients for each of the markers is presented at the final study visit.
Time frame: 0-48 weeks
Physicians were asked the following question to be rated on a seven-point scale: "How has the subject's spasticity changed since Visit 1?" The markers were: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better. The number of patients for each of the markers is presented at the final study visit.
Publications
No exact PMID-linked public article is currently readable locally.
The BDI-II is a multiple choice self-reported inventory that is one of the most widely used instruments for measuring the severity of depression. There are 21 questions or items, each having four possible responses. Each response is assigned a score ranging from zero to three, indicating the severity of the symptom. Items 1 to 13 assess symptoms that are psychological in nature, while items 14 to 21 assess symptoms that are more physical. The sum of all BDI-II item scores indicates the severity of depression. For patients eligible for this study, a score of 21 or over represents depression. The BDI-II can distinguish between different subtypes of depressive disorders, such as major depression and dysthymia. A reduction in score indicates an improvement in condition.
Population: All randomized patients who received at least one dose of study medication and yielded on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 57 | -3.1 | 7.76 |
| Placebo | 56 | -2.4 | 6.38 |
Patients were asked the following question, to be rated on a seven-point scale: "Please assess the change in your spasticity since immediately before receiving the first dose of study treatment (Visit 1) using the scale below". The markers were: 'Very much worse', 'Much worse', 'Minimally worse', 'No change', 'Minimally better', 'Much better' or 'Very much better'. The number of patients for each of the markers is presented at the final study visit.
Population: All randomized patients who received at least one dose of study medication and yielded on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 58 | 2 | - |
| Placebo | 56 | 0 | - |
| Sativex | 58 | 16 | - |
| Placebo | 56 | 6 | - |
| Sativex | 58 | 24 | - |
| Placebo | 56 | 15 | - |
| Sativex | 58 | 13 | - |
| Placebo | 56 | 27 | - |
| Sativex | 58 | 1 | - |
| Placebo | 56 | 7 | - |
| Sativex | 58 | 2 | - |
| Placebo | 56 | 1 | - |
| Sativex | 58 | 0 | - |
| Placebo | 56 | 0 | - |
Caregivers were asked the following question to be rated on a seven-point scale: "How has the subject's spasticity changed since Visit 1?" The markers were: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better. The number of patients for each of the markers is presented at the final study visit.
Population: All randomized patients who received at least one dose of study medication and yielded on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 41 | 1 | - |
| Placebo | 40 | 0 | - |
| Sativex | 41 | 12 | - |
| Placebo | 40 | 6 | - |
| Sativex | 41 | 14 | - |
| Placebo | 40 | 10 | - |
| Sativex | 41 | 11 | - |
| Placebo | 40 | 18 | - |
| Sativex | 41 | 3 | - |
| Placebo | 40 | 3 | - |
| Sativex | 41 | 0 | - |
| Placebo | 40 | 3 | - |
| Sativex | 41 | 0 | - |
| Placebo | 40 | 0 | - |
Physicians were asked the following question to be rated on a seven-point scale: "How has the subject's spasticity changed since Visit 1?" The markers were: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better. The number of patients for each of the markers is presented at the final study visit.
Population: All randomized patients who received at least one dose of study medication and yielded on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 58 | 0 | - |
| Placebo | 56 | 1 | - |
| Sativex | 58 | 15 | - |
| Placebo | 56 | 6 | - |
| Sativex | 58 | 26 | - |
| Placebo | 56 | 15 | - |
| Sativex | 58 | 14 | - |
| Placebo | 56 | 29 | - |
| Sativex | 58 | 3 | - |
| Placebo | 56 | 4 | - |
| Sativex | 58 | 0 | - |
| Placebo | 56 | 1 | - |
| Sativex | 58 | 0 | - |
| Placebo | 56 | 0 | - |
All 20 muscle groups were assessed for spasticity (using a 0-5 scale): 0= 'no increase in muscle tone' to 5= 'affected part(s) rigid in flexion or extension'. The score for all 20 muscle groups were added to give a total score out of 100. A decrease in score indicates an improvement in condition.
Population: All randomized patients who received at least one dose of study medication and yielded on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 58 | -10.6 | 11.26 |
| Placebo | 56 | -7.7 | 10.70 |
At baseline, patients were asked how many times they had visited a healthcare professional in the previous 12 weeks. At subsequent visits, patients were asked how many times they had visited a healthcare professional since their last study visit. The change from baseline to the end of treatment is presented. A decrease in number indicates an improvement in condition.
Population: All randomized patients who received at least one dose of study medication and yielded on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 58 | -0.6 | 0.99 |
| Placebo | 56 | -0.4 | 1.30 |
Patients were scored at each clinic visit for the following outcomes using the C-SSRS: suicidal ideation, suicidal behaviour, suicidality (including complete suicidality). Possible flags were as follows: "Wish to be Dead", "Non-specific Active Suicidal Thoughts", "Active Suicidal Ideation Without Intent", "Active Suicidal Ideation With Intent, No Plan", "Active Suicidal Ideation With Intent and Plan". The number of patients with a treatment-emergent flag is presented.
Population: All randomized patients who received at least one dose of study medication and yielded on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 62 | 0 | - |
| Placebo | 59 | 2 | - |
| Sativex | 62 | 0 | - |
| Placebo | 59 | 1 | - |
| Sativex | 62 | 0 | - |
| Placebo | 59 | 1 | - |
| Sativex | 62 | 0 | - |
| Placebo | 59 | 0 | - |
| Sativex | 62 | 0 | - |
| Placebo | 59 | 0 | - |
Only those patients for whom it was appropriate (i.e. ambulatory patients) were timed for how long it took to walk 10 metres. If a patient started the 10-meter walk but was unable to complete it, an estimated time for completion was calculated based on the available data. A negative difference from baseline indicates an improvement in condition.
Population: All randomized patients who received at least one dose of study medication and yielded on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 47 | 6.2 | 55.34 |
| Placebo | 50 | 3.0 | 24.68 |
The number of subjects who experienced an adverse event during the course of the study is presented.
Population: All randomized patients who received at least one dose of study medication and yielded on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 62 | 39 | - |
| Placebo | 59 | 19 | - |
| Milestone | Sativex | Placebo |
|---|---|---|
| STARTED | 62 | 59 |
| COMPLETED | 50 | 48 |
| NOT COMPLETED | 12 | 11 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Acute Myocardial Infarction | Cardiac disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Inguinal Hernia | Gastrointestinal disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Drug Withdrawal Syndrome | General disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Bronchitis | Infections and infestations | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Pneumonia | Infections and infestations | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Overdose | Injury, poisoning and procedural complications | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Tetany | Metabolism and nutrition disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Dysarthria | Nervous system disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Disorientation | Psychiatric disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Vertigo | Ear and labyrinth disorders | Sativex: 6 / 62 · Placebo: 0 / 59 |
| Visual Impairment | Eye disorders | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Diarrhoea | Gastrointestinal disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Dry Mouth | Gastrointestinal disorders | Sativex: 2 / 62 · Placebo: 0 / 59 |
| Gingivitis | Gastrointestinal disorders | Sativex: 0 / 62 · Placebo: 2 / 59 |
| Nausea | Gastrointestinal disorders | Sativex: 1 / 62 · Placebo: 1 / 59 |
| Oral Mucosal Erythema | Gastrointestinal disorders | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Vomiting | Gastrointestinal disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Asthenia | General disorders | Sativex: 2 / 62 · Placebo: 0 / 59 |
| Fatigue | General disorders | Sativex: 5 / 62 · Placebo: 1 / 59 |
| Pyrexia | General disorders | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Drug Hypersensitivity | Immune system disorders | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Bacterial Infection | Infections and infestations | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Herpes Zoster | Infections and infestations | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Subcutaneous Abscess | Infections and infestations | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Tonsillitis | Infections and infestations | Sativex: 2 / 62 · Placebo: 0 / 59 |
| Upper Respiratory Tract Infection | Infections and infestations | Sativex: 0 / 62 · Placebo: 3 / 59 |
| Upper Respiratory Tract Infection Bacterial | Infections and infestations | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Urinary Tract Infection | Infections and infestations | Sativex: 5 / 62 · Placebo: 1 / 59 |
| Viral Infection | Infections and infestations | Sativex: 0 / 62 · Placebo: 2 / 59 |
| Contusion | Injury, poisoning and procedural complications | Sativex: 1 / 62 · Placebo: 1 / 59 |
| Face Injury | Injury, poisoning and procedural complications | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Foot Fracture | Injury, poisoning and procedural complications | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Forearm Fracture | Injury, poisoning and procedural complications | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Joint Dislocation | Injury, poisoning and procedural complications | Sativex: 1 / 62 · Placebo: 1 / 59 |
| Ligament Sprain | Injury, poisoning and procedural complications | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Lower Limb Fracture | Injury, poisoning and procedural complications | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Procedural Vomiting | Injury, poisoning and procedural complications | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Thermal Burn | Injury, poisoning and procedural complications | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Upper Limb Fracture | Injury, poisoning and procedural complications | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Blood Alkaline Phosphatase Increased | Investigations | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Vitamin D Decreased | Investigations | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Weight Decreased | Investigations | Sativex: 3 / 62 · Placebo: 0 / 59 |
| Decreased Appetite | Metabolism and nutrition disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Back Pain | Musculoskeletal and connective tissue disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Muscle Spasms | Musculoskeletal and connective tissue disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Pain In Extremity | Musculoskeletal and connective tissue disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Cerebellar Ataxia | Nervous system disorders | Sativex: 2 / 62 · Placebo: 0 / 59 |
| Cognitive Disorder | Nervous system disorders | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Dizziness | Nervous system disorders | Sativex: 5 / 62 · Placebo: 0 / 59 |
| Headache | Nervous system disorders | Sativex: 1 / 62 · Placebo: 2 / 59 |
| Memory Impairment | Nervous system disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Multiple Sclerosis | Nervous system disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Multiple Sclerosis Relapse | Nervous system disorders | Sativex: 3 / 62 · Placebo: 4 / 59 |
| Muscle Spasticity | Nervous system disorders | Sativex: 5 / 62 · Placebo: 2 / 59 |
| Neuralgia | Nervous system disorders | Sativex: 2 / 62 · Placebo: 0 / 59 |
| Paraesthesia | Nervous system disorders | Sativex: 1 / 62 · Placebo: 1 / 59 |
| Paraparesis | Nervous system disorders | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Radiculopathy | Nervous system disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Somnolence | Nervous system disorders | Sativex: 1 / 62 · Placebo: 1 / 59 |
| Stupor | Nervous system disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Tremor | Nervous system disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Trigeminal Neuralgia | Nervous system disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Anxiety Disorder Due To A General Medical Condition | Psychiatric disorders | Sativex: 2 / 62 · Placebo: 0 / 59 |
| Euphoric Mood | Psychiatric disorders | Sativex: 2 / 62 · Placebo: 0 / 59 |
| Suicidal Ideation | Psychiatric disorders | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Erectile Dysfunction | Reproductive system and breast disorders | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Oropharyngeal Blistering | Respiratory, thoracic and mediastinal disorders | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Dermatitis Allergic | Skin and subcutaneous tissue disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Lipoma Excision | Surgical and medical procedures | Sativex: 0 / 62 · Placebo: 1 / 59 |
| Tooth Extraction | Surgical and medical procedures | Sativex: 1 / 62 · Placebo: 0 / 59 |
| Application Site Discomfort | General disorders | Sativex: 1 / 62 · Placebo: 0 / 59 |
Time frame: 0-48 weeks
All 20 muscle groups were assessed for spasticity (using a 0-5 scale): 0= 'no increase in muscle tone' to 5= 'affected part(s) rigid in flexion or extension'. The score for all 20 muscle groups were added to give a total score out of 100. A decrease in score indicates an improvement in condition.
Time frame: 0-48 weeks
At baseline, patients were asked how many times they had visited a healthcare professional in the previous 12 weeks. At subsequent visits, patients were asked how many times they had visited a healthcare professional since their last study visit. The change from baseline to the end of treatment is presented. A decrease in number indicates an improvement in condition.
Time frame: 0-48 weeks
Patients were scored at each clinic visit for the following outcomes using the C-SSRS: suicidal ideation, suicidal behaviour, suicidality (including complete suicidality). Possible flags were as follows: "Wish to be Dead", "Non-specific Active Suicidal Thoughts", "Active Suicidal Ideation Without Intent", "Active Suicidal Ideation With Intent, No Plan", "Active Suicidal Ideation With Intent and Plan". The number of patients with a treatment-emergent flag is presented.
Time frame: 0-48 weeks
Only those patients for whom it was appropriate (i.e. ambulatory patients) were timed for how long it took to walk 10 metres. If a patient started the 10-meter walk but was unable to complete it, an estimated time for completion was calculated based on the available data. A negative difference from baseline indicates an improvement in condition.
Time frame: 0-50 weeks
The number of subjects who experienced an adverse event during the course of the study is presented.