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The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in relieving peripheral neuropathic pain associated with allodynia.
Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2023-04-12
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
This was a six week, multicentre, double blind, randomised, placebo controlled parallel group study to evaluate the efficacy of Sativex®. Subjects with peripheral neuropathic pain characterised by allodynia, were screened to determine eligibility and entered a seven day baseline period. Subjects then returned to the centre for randomisation and dose introduction, and received either placebo or Sativex in a double blind manner for five weeks, with a follow up visit 7 to 10 days after the end of the treatment period. The primary efficacy measure was the difference in pain severity at the end of treatment, measured using a peripheral neuropathic pain 0 to 10 numerical rating scale.
Linked local records
Local links use governed condition terms or exact source-reported intervention names. They are navigation candidates, not efficacy claims.
Interventions
containing THC (27 mg/ml):CBD (25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Maximum permitted dose was eight actuations in any three hour period and 24 actuations (THC 65 mg: CBD 60 mg) in 24 hours
GW-1000-02containing peppermint oil, 0.05% (v/v), quinoline yellow, 0.005% (w/v), sunset yellow, 0.0025% (w/v), in ethanol:propylene glycol (50:50) excipient.
GW-4001-01Source-reported results
Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.
The neuropathic pain Numerical Rating Scale was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = worst possible pain. A negative value indicates an improvement in pain score from baseline.
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 61 | -1.57 | 2.11 |
| Placebo | 62 | -0.59 | 1.38 |
The Neuropathic Pain Scale (NPS) score consisted of a series of assessments of different aspects of pain (intensity, sharpness, hot, dull, cold, sensitive, itchy, unpleasantness, and surface compared with deep), each scored using 11-point Numerical Rating Scales. The NPS score is 0-100 sum of 10 individual pain scores (0-10 NRS, 0= no pain to 10 = most pain imaginable). A negative change from baseline indicates an improvement in pain.
Eligibility
primary outcomes
Time frame: Day 0 to Day 42
The neuropathic pain Numerical Rating Scale was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = worst possible pain. A negative value indicates an improvement in pain score from baseline.
secondary outcomes
Time frame: Day 0 to Day 42
The Neuropathic Pain Scale (NPS) score consisted of a series of assessments of different aspects of pain (intensity, sharpness, hot, dull, cold, sensitive, itchy, unpleasantness, and surface compared with deep), each scored using 11-point Numerical Rating Scales. The NPS score is 0-100 sum of 10 individual pain scores (0-10 NRS, 0= no pain to 10 = most pain imaginable). A negative change from baseline indicates an improvement in pain.
Time frame: Day 7 - Day 42
The sleep disruption NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate how your pain disrupted your sleep last night?" where 0 = did not disrupt sleep and 10 = completely disrupted (unable to sleep at all). A negative value indicates an improvement in sleep disruption score from baseline.
Time frame: Day 0 - Day 42
The Pain Disability Index consisted of seven self-administered questions relating to the effect of the subject's chronic pain on their personal life (family/home responsibilities, social activity, sexual behaviour, life-support activity, recreation, occupation and self-care). Each assessment was scored on an 11-point Numerical Rating Scale ranging from 0 (which equals 'no disability') to 10 (which equals 'total disability'). The total Pain Disability Index is the unweighted sum of the seven Numerical Rating Scale scores. The maximum (worst) total score was 70.
Time frame: Day 7 and Day 42
Dynamic allodynia was assessed by stroking the skin over the affected area five times with a standardised brush, designed specifically for sensory testing at 5sec intervals, and recording the pain severity on a 0-10 point scale (0= no pain to 10 = most pain imaginable). All strokes were of the same length, minimum 2 cm. Each dynamic allodynia score was calculated as the average of the five strokes. A negative change from baseline indicates an improvement in score.
Publications
No exact PMID-linked public article is currently readable locally.
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 59 | -9.7 | 19.35 |
| Placebo | 62 | -2.0 | 12.14 |
The sleep disruption NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate how your pain disrupted your sleep last night?" where 0 = did not disrupt sleep and 10 = completely disrupted (unable to sleep at all). A negative value indicates an improvement in sleep disruption score from baseline.
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 61 | -0.82 | 0.76 |
| Placebo | 62 | -0.38 | 0.68 |
The Pain Disability Index consisted of seven self-administered questions relating to the effect of the subject's chronic pain on their personal life (family/home responsibilities, social activity, sexual behaviour, life-support activity, recreation, occupation and self-care). Each assessment was scored on an 11-point Numerical Rating Scale ranging from 0 (which equals 'no disability') to 10 (which equals 'total disability'). The total Pain Disability Index is the unweighted sum of the seven Numerical Rating Scale scores. The maximum (worst) total score was 70.
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 53 | -5.6 | 12.08 |
| Placebo | 57 | 0.3 | 8.71 |
Dynamic allodynia was assessed by stroking the skin over the affected area five times with a standardised brush, designed specifically for sensory testing at 5sec intervals, and recording the pain severity on a 0-10 point scale (0= no pain to 10 = most pain imaginable). All strokes were of the same length, minimum 2 cm. Each dynamic allodynia score was calculated as the average of the five strokes. A negative change from baseline indicates an improvement in score.
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 55 | -1.15 | 2.23 |
| Placebo | 51 | -0.38 | 1.72 |
The static allodynia test involved applying pressure to a non-allodynic area (on the contralateral side to the identified allodynic area), and recording the pressure that caused pain to this area. Seventy five percent of the pressure that caused pain to the non-allodynic area (up to the subject's pain/pressure threshold) was then applied to the allodynic area, and an 11-point Numerical Rating Scale pain score recorded (between 0 (no pain)and 10 (most intense pain imaginable)). A negative value indicates an improvement in pain score from baseline.
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 56 | 18.22 | 50.20 |
| Placebo | 62 | 2.84 | 44.43 |
The General Health Questionnaire-12 is designed to measure non-psychotic mental disorders. It consists of 12 questions, scored on a 0 to 3 Likert scale to measure and compare psychological morbidity levels, where 0 represents better psychological health. The total General Health Questionnaire-12 score is the unweighted sum of the 12 scores. Zero indicates the best possible psychological health, 36 indicates the worst possible psychological health.
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 60 | -3.0 | 7.93 |
| Placebo | 62 | -2.6 | 5.72 |
The Selective Reminding Test measures verbal learning and delayed recall through a multiple-trial list-learning paradigm. Patients are presented aurally with a list of 12 words for trial 1 and are asked to recall as many as possible. For trials 2-6, there is a selective presentation of only those words not recalled on the previous trial. Trial 7 is similar to the other trials but is assessed after an 11-minute delay. The score for the selective reminding test is the unweighted average of seven individual study results (min=0 and max=84) Higher scores indicate a better cognitive performance.
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 40 | 0.53 | 1.10 |
| Placebo | 42 | 0.48 | 1.27 |
The 10/36 Spatial Recall Test assesses visual spatial learning and delayed recall. Patients are asked to view a 6 x 6 checkerboard with ten checkers for 10 seconds. They are then asked to recreate the pattern viewed on a blank checkerboard. The number of correct responses from three immediate trials and one delayed trial (7 minute delay) are recorded. The Total number of correct responses is the unweighted sum from the four trials. The score for the 10/36 spatial recall test was the unweighted average of four individual study results (min=0 and max=40). A higher score indicates better cognitive performance.
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 39 | 0.79 | 2.01 |
| Placebo | 42 | 0.15 | 2.12 |
The Symbol Digit Modalities Test measures complex attention and concentration in a task which also requires speed and accuracy in visual search and scanning. Patients are required to associate symbols with numbers and quickly generate the number when shown the symbol. The summary endpoint is the number of correct responses in 90 seconds. The symbol digit modalities test had a min of 0 and max score of 99. A higher score indicates better cognitive performance.
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 39 | 1.6 | 5.83 |
| Placebo | 42 | 3.9 | 7.38 |
The Paced Auditory Serial Addition Task assesses sustained attention and concentration. A pre-recorded tape is used to present two series of 60 numbers, one every 3 seconds and one every 2 seconds. Patients are asked to add each number to the one immediately preceding it and give the result. The task summary score is the percentage of correct answers is calculated. The PASAT score range was 0% to 100%. Higher scores indicate a better cognitive
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 24 | 8.0 | 14.23 |
| Placebo | 29 | 6.3 | 9.25 |
Word list generation measures verbal associative fluency. Patients are given 60 seconds to give as many words beginning with a particular letter. The Total is the unweighted sum of all admissible words over three different trials. Higher scores indicate a better cognitive performance (min=0, max= not defined).
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 38 | 3.5 | 7.67 |
| Placebo | 41 | 3.5 | 8.47 |
Subjects were asked to give their impression of the overall change in their peripheral neuropathic pain since entry into the study using the following seven-point scale: 1 = 'Very Much Improved', 2 = 'Much Improved', 3 = 'Minimally Improved', 4 = 'No Change', 5 = 'Minimally Worse', 6 = 'Much Worse', 7 = 'Very Much Worse'. The number of subjects who reported an improvement is presented.
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 63 | 5 | - |
| Placebo | 62 | 0 | - |
| Sativex | 63 | 11 | - |
| Placebo | 62 | 6 | - |
| Sativex | 63 | 16 | - |
| Placebo | 62 | 6 | - |
| Sativex | 63 | 26 | - |
| Placebo | 62 | 46 | - |
| Sativex | 63 | 0 | - |
| Placebo | 62 | 2 | - |
| Sativex | 63 | 4 | - |
| Placebo | 62 | 2 | - |
| Sativex | 63 | 0 | - |
| Placebo | 62 | 0 | - |
| Sativex | 63 | 1 | - |
| Placebo | 62 | 0 | - |
Intoxication scores were measured using a 100 mm Visual Analogue Scale, where 0 equalled 'no intoxication' and 100 equalled 'extreme intoxication'. A negative value indicates an improvement in intoxication score from baseline.
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 62 | 3.2 | 11.39 |
| Placebo | 62 | 1.4 | 10.74 |
Subjects were asked to give their impression of the overall change in their allodynia since entry into the study using the following seven-point scale: 1 = 'Very Much Improved', 2 = 'Much Improved', 3 = 'Minimally Improved', 4 = 'No Change', 5 = 'Minimally Worse', 6 = 'Much Worse', 7 = 'Very Much Worse'. A summary of the number and percentage of subjects
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 63 | 3 | - |
| Placebo | 62 | 0 | - |
| Sativex | 63 | 12 | - |
| Placebo | 62 | 3 | - |
| Sativex | 63 | 14 | - |
| Placebo | 62 | 8 | - |
| Sativex | 63 | 30 | - |
| Placebo | 62 | 47 | - |
| Sativex | 63 | 1 | - |
| Placebo | 62 | 2 | - |
| Sativex | 63 | 2 | - |
| Placebo | 62 | 2 | - |
| Sativex | 63 | 0 | - |
| Placebo | 62 | 0 | - |
| Sativex | 63 | 1 | - |
| Placebo | 62 | 0 | - |
The number of subjects who reported an adverse event during the course of the study is presented
Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 63 | 57 | - |
| Placebo | 62 | 48 | - |
| Milestone | Sativex | Placebo |
|---|---|---|
| STARTED | 63 | 62 |
| COMPLETED | 50 | 55 |
| NOT COMPLETED | 13 | 7 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Fall | General disorders | Sativex: 0 / 63 · Placebo: 1 / 62 |
| Bronchopneumonia | Infections and infestations | Sativex: 1 / 63 · Placebo: 0 / 62 |
| Transient ischaemic attack | Nervous system disorders | Sativex: 1 / 63 · Placebo: 0 / 62 |
| Hypoaesthesia | Nervous system disorders | Sativex: 0 / 63 · Placebo: 0 / 62 |
| Myelitis NOS | Nervous system disorders | Sativex: 0 / 63 · Placebo: 1 / 62 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Dizziness | Nervous system disorders | Sativex: 18 / 63 · Placebo: 9 / 62 |
| Nausea | Gastrointestinal disorders | Sativex: 14 / 63 · Placebo: 7 / 62 |
| Fatigue | General disorders | Sativex: 13 / 63 · Placebo: 5 / 62 |
| Dry Mouth | Gastrointestinal disorders | Sativex: 11 / 63 · Placebo: 3 / 62 |
| Vomiting Not Otherwise Specified (NOS) | Gastrointestinal disorders | Sativex: 8 / 63 · Placebo: 3 / 62 |
| Feeling drunk | General disorders | Sativex: 6 / 63 · Placebo: 0 / 62 |
| Headache NOS | Nervous system disorders | Sativex: 6 / 63 · Placebo: 9 / 62 |
| Diarrhoea NOS | Gastrointestinal disorders | Sativex: 4 / 63 · Placebo: 0 / 62 |
| Nasopharyngitis | Infections and infestations | Sativex: 4 / 63 · Placebo: 2 / 62 |
| Anorexia | Metabolism and nutrition disorders | Sativex: 4 / 63 · Placebo: 0 / 62 |
| Somnolence | Nervous system disorders | Sativex: 4 / 63 · Placebo: 0 / 62 |
| Abdominal pain upper | Gastrointestinal disorders | Sativex: 3 / 63 · Placebo: 0 / 62 |
| Disturbance in attention | Nervous system disorders | Sativex: 3 / 63 · Placebo: 0 / 62 |
| Memory impairment | Nervous system disorders | Sativex: 3 / 63 · Placebo: 0 / 62 |
| Fall | General disorders | Sativex: 0 / 63 · Placebo: 3 / 62 |
| Hypoaesthesia | Nervous system disorders | Sativex: 0 / 63 · Placebo: 3 / 62 |
| Vision Blurred | Eye disorders | Sativex: 2 / 63 · Placebo: 0 / 62 |
| Oral Pain | Gastrointestinal disorders | Sativex: 0 / 63 · Placebo: 2 / 62 |
| Dyspepsia | Gastrointestinal disorders | Sativex: 0 / 63 · Placebo: 2 / 62 |
| Lethargy | General disorders | Sativex: 2 / 63 · Placebo: 0 / 62 |
| Malaise | General disorders | Sativex: 2 / 63 · Placebo: 0 / 62 |
| Blood Glucose Increased | Investigations | Sativex: 2 / 63 · Placebo: 0 / 62 |
| Blood Alkaline Phosphatase NOS Increased | Investigations | Sativex: 0 / 63 · Placebo: 2 / 62 |
| Hunger | Metabolism and nutrition disorders | Sativex: 2 / 63 · Placebo: 0 / 62 |
| Arthralgia | Musculoskeletal and connective tissue disorders | Sativex: 0 / 63 · Placebo: 2 / 62 |
| Agitation | Psychiatric disorders | Sativex: 2 / 63 · Placebo: 0 / 62 |
| Euphoric Mood | Psychiatric disorders | Sativex: 2 / 63 · Placebo: 0 / 62 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Sativex: 2 / 63 · Placebo: 0 / 62 |
| Pharyngitis | Respiratory, thoracic and mediastinal disorders | Sativex: 2 / 63 · Placebo: 2 / 62 |
| Constipation | Gastrointestinal disorders | Sativex: 2 / 63 · Placebo: 4 / 62 |
| Application Site Burning | General disorders | Sativex: 2 / 63 · Placebo: 4 / 62 |
| Application Site Pain | General disorders | Sativex: 4 / 63 · Placebo: 2 / 62 |
Time frame: Day 0 - Day 42
The static allodynia test involved applying pressure to a non-allodynic area (on the contralateral side to the identified allodynic area), and recording the pressure that caused pain to this area. Seventy five percent of the pressure that caused pain to the non-allodynic area (up to the subject's pain/pressure threshold) was then applied to the allodynic area, and an 11-point Numerical Rating Scale pain score recorded (between 0 (no pain)and 10 (most intense pain imaginable)). A negative value indicates an improvement in pain score from baseline.
Time frame: Day 7 and Day 42
The General Health Questionnaire-12 is designed to measure non-psychotic mental disorders. It consists of 12 questions, scored on a 0 to 3 Likert scale to measure and compare psychological morbidity levels, where 0 represents better psychological health. The total General Health Questionnaire-12 score is the unweighted sum of the 12 scores. Zero indicates the best possible psychological health, 36 indicates the worst possible psychological health.
Time frame: Day 7 and Day 42
The Selective Reminding Test measures verbal learning and delayed recall through a multiple-trial list-learning paradigm. Patients are presented aurally with a list of 12 words for trial 1 and are asked to recall as many as possible. For trials 2-6, there is a selective presentation of only those words not recalled on the previous trial. Trial 7 is similar to the other trials but is assessed after an 11-minute delay. The score for the selective reminding test is the unweighted average of seven individual study results (min=0 and max=84) Higher scores indicate a better cognitive performance.
Time frame: Day 7 and Day 42
The 10/36 Spatial Recall Test assesses visual spatial learning and delayed recall. Patients are asked to view a 6 x 6 checkerboard with ten checkers for 10 seconds. They are then asked to recreate the pattern viewed on a blank checkerboard. The number of correct responses from three immediate trials and one delayed trial (7 minute delay) are recorded. The Total number of correct responses is the unweighted sum from the four trials. The score for the 10/36 spatial recall test was the unweighted average of four individual study results (min=0 and max=40). A higher score indicates better cognitive performance.
Time frame: Day 7 and Day 42
The Symbol Digit Modalities Test measures complex attention and concentration in a task which also requires speed and accuracy in visual search and scanning. Patients are required to associate symbols with numbers and quickly generate the number when shown the symbol. The summary endpoint is the number of correct responses in 90 seconds. The symbol digit modalities test had a min of 0 and max score of 99. A higher score indicates better cognitive performance.
Time frame: Day 7 and Day 42
The Paced Auditory Serial Addition Task assesses sustained attention and concentration. A pre-recorded tape is used to present two series of 60 numbers, one every 3 seconds and one every 2 seconds. Patients are asked to add each number to the one immediately preceding it and give the result. The task summary score is the percentage of correct answers is calculated. The PASAT score range was 0% to 100%. Higher scores indicate a better cognitive
Time frame: Day 7 and Day 42
Word list generation measures verbal associative fluency. Patients are given 60 seconds to give as many words beginning with a particular letter. The Total is the unweighted sum of all admissible words over three different trials. Higher scores indicate a better cognitive performance (min=0, max= not defined).
Time frame: Day 42
Subjects were asked to give their impression of the overall change in their peripheral neuropathic pain since entry into the study using the following seven-point scale: 1 = 'Very Much Improved', 2 = 'Much Improved', 3 = 'Minimally Improved', 4 = 'No Change', 5 = 'Minimally Worse', 6 = 'Much Worse', 7 = 'Very Much Worse'. The number of subjects who reported an improvement is presented.
Time frame: Day 0 - Day 42
Intoxication scores were measured using a 100 mm Visual Analogue Scale, where 0 equalled 'no intoxication' and 100 equalled 'extreme intoxication'. A negative value indicates an improvement in intoxication score from baseline.
Time frame: Day 0 - 42
Subjects were asked to give their impression of the overall change in their allodynia since entry into the study using the following seven-point scale: 1 = 'Very Much Improved', 2 = 'Much Improved', 3 = 'Minimally Improved', 4 = 'No Change', 5 = 'Minimally Worse', 6 = 'Much Worse', 7 = 'Very Much Worse'. A summary of the number and percentage of subjects
Time frame: Day 0 - Day 42
The number of subjects who reported an adverse event during the course of the study is presented