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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 2023-05-03
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 15 week (one week baseline and fourteen weeks treatment period), multicentre, double blind, randomised, placebo controlled, parallel group study to evaluate the efficacy of Sativex® in subjects with PNP, associated with allodynia. Subjects were screened to determine eligibility and completed a seven-day baseline period. Subjects then returned to the centre for assessment, randomisation and dose introduction. Visits occurred at the end of weeks two, six, ten and at the end of the study (treatment week 14) or earlier if they withdrew. A follow up visit occurred 28 days after completion or withdrawal. Subjects in this study were given the opportunity to be enrolled in an open label extension study.
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 peripheral neuropathic pain 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 the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain. A negative value indicates an improvement in pain score from baseline.
Population: The efficacy analyses were conducted on data from all subjects who were randomised, received at least one dose of study medication and yielded on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 77 | -1.36 | 2.02 |
| Placebo | 92 | -0.84 | 1.86 |
Eligibility
primary outcomes
Time frame: Day 7 to Day 98
The peripheral neuropathic pain 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 the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain. A negative value indicates an improvement in pain score from baseline.
secondary outcomes
Time frame: Day 7 to Day 98
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 to Day 98
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 7 and Day 98
Dynamic allodynia was assessed by stroking the skin over the affected area five times with a standardised brush, designed specifically for sensory testing at 5 s 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.
Time frame: Day 7 and Day 98
Punctate allodynia was measured using an in-house built pressure algometer comprising a strain gauge connected to a metal filament with a diameter of 1 mm and blunt tip at baseline and end of study. The filament was manually directed against the skin at an angle of 90 degrees and a steadily increasing pressure applied until the patient verbally indicated that they perceived pain (punctate pressure pain threshold). Patients were asked to verbally rate the intensity of the pain elicited, choosing a number between 0 (no pain)and 10 (most intense pain imaginable).
Time frame: Day 98
A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain due to peripheral neuropathy since entry into the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their pain caused by peripheral neuropathy which was used at end of treatment to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Publications
No exact PMID-linked public article is currently readable locally.
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.
Population: The primary population for the analysis of efficacy was the full analysis set, which included all randomised subjects who received at least one dose of test treatment and had on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 78 | -11.57 | 16.15 |
| Placebo | 93 | -7.19 | 19.65 |
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: The primary population for the analysis of efficacy was the full analysis set, which included all randomised subjects who received at least one dose of test treatment and had on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 81 | -2.0 | 2.70 |
| Placebo | 86 | -1.2 | 2.38 |
Dynamic allodynia was assessed by stroking the skin over the affected area five times with a standardised brush, designed specifically for sensory testing at 5 s 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: The primary population for the analysis of efficacy was the full analysis set, which included all randomised subjects who received at least one dose of test treatment and had on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 112 | -1.1 | 2.16 |
| Placebo | 102 | -1.0 | 2.49 |
Punctate allodynia was measured using an in-house built pressure algometer comprising a strain gauge connected to a metal filament with a diameter of 1 mm and blunt tip at baseline and end of study. The filament was manually directed against the skin at an angle of 90 degrees and a steadily increasing pressure applied until the patient verbally indicated that they perceived pain (punctate pressure pain threshold). Patients were asked to verbally rate the intensity of the pain elicited, choosing a number between 0 (no pain)and 10 (most intense pain imaginable).
Population: The primary population for the analysis of efficacy was the full analysis set, which included all randomised subjects who received at least one dose of test treatment and had on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 112 | 0.2 | 0.78 |
| Placebo | 106 | 0.3 | 1.08 |
A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain due to peripheral neuropathy since entry into the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their pain caused by peripheral neuropathy which was used at end of treatment to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Population: The primary population for the analysis of efficacy was the full analysis set, which included all randomised subjects who received at least one dose of test treatment and had on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 117 | 8 | - |
| Placebo | 111 | 4 | - |
| Sativex | 117 | 16 | - |
| Placebo | 111 | 10 | - |
| Sativex | 117 | 38 | - |
| Placebo | 111 | 24 | - |
| Sativex | 117 | 44 | - |
| Placebo | 111 | 66 | - |
| Sativex | 117 | 9 | - |
| Placebo | 111 | 4 | - |
| Sativex | 117 | 2 | - |
| Placebo | 111 | 3 | - |
The BPI-SF is a 14-item questionnaire that asks patients to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items(range 0-10). The minimum value is zero and maximum is 10. A higher score represents a poor outcome.
Population: The primary population for the analysis of efficacy was the full analysis set, which included all randomised subjects who received at least one dose of test treatment and had on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 114 | -0.9 | 1.69 |
| Placebo | 105 | -0.6 | 1.90 |
The EQ-5D questionnaire provided two outcomes:(1)A weighted health state index visual analogue scale (VAS); (2) A self-rated health status VAS. EQ-5D Health Status VAS Scale: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.The weighted health state index used the same VAS as above but was calculated for each assessment without imputation to account for missing values i.e., if one or more individual items was missing then the whole index was missing.
Population: The primary population for the analysis of efficacy was the full analysis set, which included all randomised subjects who received at least one dose of test treatment and had on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 113 | 0.037 | 0.187 |
| Placebo | 107 | 0.044 | 0.214 |
The EQ-5D questionnaire provided two outcomes:(1)A weighted health state index visual analogue scale (VAS); (2) A self-rated health status VAS. EQ-5D Health Status VAS Scale: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.
Population: The primary population for the analysis of efficacy was the full analysis set, which included all randomised subjects who received at least one dose of test treatment and had on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 111 | 3.7 | 20.6 |
| Placebo | 105 | 2.5 | 21.2 |
Use of break through medication was recorded daily during the study as the number of paracetamol tablets taken. The change in mean daily quantities of tablets used was calculated from baseline to the last seven days of treatment.
Population: The primary population for the analysis of efficacy was the full analysis set, which included all randomised subjects who received at least one dose of test treatment and had on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 77 | -0.99 | 2.20 |
| Placebo | 92 | -0.47 | 2.08 |
The number of subjects that reported an adverse event in this study is presented.
Population: All subjects were included in this analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 128 | 109 | - |
| Placebo | 118 | 83 | - |
| Milestone | Sativex | Placebo |
|---|---|---|
| STARTED | 128 | 118 |
| COMPLETED | 79 | 94 |
| NOT COMPLETED | 49 | 24 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Bronchopneumonia | Infections and infestations | Sativex: 1 / 128 · Placebo: 0 / 118 |
| Infective Exacerbation of Chronic Obstructive Airway Disease | Infections and infestations | Sativex: 1 / 128 · Placebo: 0 / 118 |
| Pneumonia | Infections and infestations | Sativex: 1 / 128 · Placebo: 0 / 118 |
| Subcutaneous Abscess | Infections and infestations | Sativex: 1 / 128 · Placebo: 0 / 118 |
| Urinary Tract Infection | Infections and infestations | Sativex: 1 / 128 · Placebo: 0 / 118 |
| Transient Ischaemic Attack | Nervous system disorders | Sativex: 1 / 128 · Placebo: 0 / 118 |
| Coma | Nervous system disorders | Sativex: 0 / 128 · Placebo: 1 / 118 |
| Dizziness | Nervous system disorders | Sativex: 0 / 128 · Placebo: 1 / 118 |
| Loss of Consciousness | Nervous system disorders | Sativex: 0 / 128 · Placebo: 1 / 118 |
| Breast Cancer Stage II | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Sativex: 1 / 128 · Placebo: 0 / 118 |
| Malignant Melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Sativex: 1 / 128 · Placebo: 0 / 118 |
| Neoplasm Malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Sativex: 1 / 128 · Placebo: 0 / 118 |
| Myocardial Infarction | Cardiac disorders | Sativex: 1 / 128 · Placebo: 0 / 118 |
| Inguinal Hernia | Gastrointestinal disorders | Sativex: 1 / 128 · Placebo: 0 / 118 |
| Enterovesical Fistula | Gastrointestinal disorders | Sativex: 0 / 128 · Placebo: 1 / 118 |
| Chest Pain | General disorders | Sativex: 1 / 128 · Placebo: 0 / 118 |
| Head Injury | Injury, poisoning and procedural complications | Sativex: 0 / 128 · Placebo: 1 / 118 |
| Joint Dislocation | Injury, poisoning and procedural complications | Sativex: 0 / 128 · Placebo: 1 / 118 |
| Lumbar Vertebral fracture | Injury, poisoning and procedural complications | Sativex: 0 / 128 · Placebo: 1 / 118 |
| Road Traffic Accident | Injury, poisoning and procedural complications | Sativex: 0 / 128 · Placebo: 1 / 118 |
| Soft Tissue Injury | Injury, poisoning and procedural complications | Sativex: 0 / 128 · Placebo: 1 / 118 |
| Deep Vein Thrombosis | Vascular disorders | Sativex: 0 / 128 · Placebo: 1 / 118 |
| Hypotension | Vascular disorders | Sativex: 0 / 128 · Placebo: 1 / 118 |
| Groin Pain | Musculoskeletal and connective tissue disorders | Sativex: 0 / 128 · Placebo: 1 / 118 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Dizziness | Nervous system disorders | Sativex: 52 / 128 · Placebo: 12 / 118 |
| Dysgeusia | Nervous system disorders | Sativex: 14 / 128 · Placebo: 2 / 118 |
| Headache | Nervous system disorders | Sativex: 13 / 128 · Placebo: 9 / 118 |
| Disturbance in Attention | Nervous system disorders | Sativex: 8 / 128 · Placebo: 2 / 118 |
| Neuropathy Peripheral | Nervous system disorders | Sativex: 6 / 128 · Placebo: 4 / 118 |
| Tremor | Nervous system disorders | Sativex: 6 / 128 · Placebo: 0 / 118 |
| Somnolence | Nervous system disorders | Sativex: 5 / 128 · Placebo: 2 / 118 |
| Balance Disorder | Nervous system disorders | Sativex: 4 / 128 · Placebo: 2 / 118 |
| Memory Impairment | Nervous system disorders | Sativex: 4 / 128 · Placebo: 2 / 118 |
| Sedation | Nervous system disorders | Sativex: 4 / 128 · Placebo: 0 / 118 |
| Nausea | Gastrointestinal disorders | Sativex: 23 / 128 · Placebo: 14 / 118 |
| Vomiting | Gastrointestinal disorders | Sativex: 13 / 128 · Placebo: 7 / 118 |
| Diarrhoea | Gastrointestinal disorders | Sativex: 12 / 128 · Placebo: 6 / 118 |
| Dry Mouth | Gastrointestinal disorders | Sativex: 11 / 128 · Placebo: 4 / 118 |
| Abdominal Pain Upper | Gastrointestinal disorders | Sativex: 6 / 128 · Placebo: 1 / 118 |
| Dyspepsia | Gastrointestinal disorders | Sativex: 6 / 128 · Placebo: 4 / 118 |
| Constipation | Gastrointestinal disorders | Sativex: 4 / 128 · Placebo: 2 / 118 |
| Mouth Ulceration | Gastrointestinal disorders | Sativex: 4 / 128 · Placebo: 6 / 118 |
| Oral Pain | Gastrointestinal disorders | Sativex: 4 / 128 · Placebo: 3 / 118 |
| Fatigue | General disorders | Sativex: 20 / 128 · Placebo: 8 / 118 |
| Feeling Drunk | General disorders | Sativex: 8 / 128 · Placebo: 3 / 118 |
| Application Site Pain | General disorders | Sativex: 7 / 128 · Placebo: 2 / 118 |
Time frame: Day 7 and Day 98
The BPI-SF is a 14-item questionnaire that asks patients to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items(range 0-10). The minimum value is zero and maximum is 10. A higher score represents a poor outcome.
Time frame: Day 7 and Day 98
The EQ-5D questionnaire provided two outcomes:(1)A weighted health state index visual analogue scale (VAS); (2) A self-rated health status VAS. EQ-5D Health Status VAS Scale: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.The weighted health state index used the same VAS as above but was calculated for each assessment without imputation to account for missing values i.e., if one or more individual items was missing then the whole index was missing.
Time frame: Day 7 and Day 98
The EQ-5D questionnaire provided two outcomes:(1)A weighted health state index visual analogue scale (VAS); (2) A self-rated health status VAS. EQ-5D Health Status VAS Scale: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.
Time frame: Days 0-7 and Days 92-98
Use of break through medication was recorded daily during the study as the number of paracetamol tablets taken. The change in mean daily quantities of tablets used was calculated from baseline to the last seven days of treatment.
Time frame: 19 weeks
The number of subjects that reported an adverse event in this study is presented.
| Dissociation | Psychiatric disorders | Sativex: 9 / 128 · Placebo: 0 / 118 |
| Disorientation | Psychiatric disorders | Sativex: 8 / 128 · Placebo: 0 / 118 |
| Depression | Psychiatric disorders | Sativex: 6 / 128 · Placebo: 0 / 118 |
| Anxiety | Psychiatric disorders | Sativex: 4 / 128 · Placebo: 1 / 118 |
| Panic Attack | Psychiatric disorders | Sativex: 4 / 128 · Placebo: 1 / 118 |
| Nasopharyngitis | Infections and infestations | Sativex: 9 / 128 · Placebo: 8 / 118 |
| Gastroenteritis | Infections and infestations | Sativex: 4 / 128 · Placebo: 1 / 118 |
| Lower Respiratory Tract Infection | Infections and infestations | Sativex: 4 / 128 · Placebo: 3 / 118 |
| Increased Appetite | Metabolism and nutrition disorders | Sativex: 6 / 128 · Placebo: 1 / 118 |
| Anorexia | Metabolism and nutrition disorders | Sativex: 4 / 128 · Placebo: 1 / 118 |
| Pharyngolaryngeal Pain | Respiratory, thoracic and mediastinal disorders | Sativex: 7 / 128 · Placebo: 5 / 118 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Sativex: 4 / 128 · Placebo: 3 / 118 |
| Rash | Skin and subcutaneous tissue disorders | Sativex: 5 / 128 · Placebo: 4 / 118 |
| Vertigo | Ear and labyrinth disorders | Sativex: 5 / 128 · Placebo: 0 / 118 |