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The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in relieving pain due to Diabetic Neuropathy.
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 pain due to diabetic neuropathy. 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 diabetic neuropathy pain Numerical Rating Scale was complete at the end of every day. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your nerve pain due to diabetes in the last 24 hours" where 0 = no pain and 10 = worst possible pain. No pain relates to the time prior to the onset of pain due to diabetic neuropathy. For those whose evaluable period ended before Day 7, the mean of the available post-randomisation data was used. Those with no post-baseline diary pain 0-10 Numerical Rating Scale scores were excluded from the analysis.
Population: The primary population for analysis was the full analysis set, which included all randomised subjects who received at least one dose of study medication and yielded on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 146 | -1.67 | 2.13 |
| Placebo | 148 | -1.55 | 2.09 |
Eligibility
primary outcomes
Time frame: Day 0 to Day 98
The diabetic neuropathy pain Numerical Rating Scale was complete at the end of every day. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your nerve pain due to diabetes in the last 24 hours" where 0 = no pain and 10 = worst possible pain. No pain relates to the time prior to the onset of pain due to diabetic neuropathy. For those whose evaluable period ended before Day 7, the mean of the available post-randomisation data was used. Those with no post-baseline diary pain 0-10 Numerical Rating Scale scores were excluded from the analysis.
Time frame: Day 0 - Day 98
A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS average pain score from baseline to week 14 (last 7 days). 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. The average pain NRS was completed at the same time each day, i.e. bedtime in the evening. Estimates were produced for a one-week period, with the evaluable period finishing at the end of the appropriate seven-day period.
secondary outcomes
Time frame: Day 0 to Day 98
The Neuropathic Pain Scale score is the 0-100 sum of 10 individual pain scores (0-10 Numerical Rating Scale, 0= no pain to 10 = most pain imaginable). A negative change from baseline indicates an improvement in pain. The baseline mean Neuropathic Pain Scale score was to be the mean of the two assessments during the baseline period, with the end of study value as the mean of the last two assessments made during the evaluable period.
Time frame: Day 0 - Day 98
The sleep quality 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 sleep quality in the last 24 hours" where 0 = slept extremely well and 10 = unable to sleep at all. A negative value indicates an improvement in pain score from baseline. The analyses were based on the change from baseline for the last assessment falling within the evaluable period (considered the end of treatment).
Time frame: Day 0 and Day 98
The subject was to assess the change in their nerve pain due to diabetic neuropathy at the end of the study compared to baseline on a 7-point scale from very much worse to very much improved. The number of participants reporting each score is presented.
Time frame: Day 0 and Day 98
The brief pain inventory (short form) 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 pain 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.
Publications
No exact PMID-linked public article is currently readable locally.
The Neuropathic Pain Scale score is the 0-100 sum of 10 individual pain scores (0-10 Numerical Rating Scale, 0= no pain to 10 = most pain imaginable). A negative change from baseline indicates an improvement in pain. The baseline mean Neuropathic Pain Scale score was to be the mean of the two assessments during the baseline period, with the end of study value as the mean of the last two assessments made during the evaluable period.
Population: The primary population for analysis was the full analysis set, which included all randomised subjects who received at least one dose of study medication and yielded on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 135 | -13.70 | 19.91 |
| Placebo | 140 | -14.16 | 17.42 |
The sleep quality 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 sleep quality in the last 24 hours" where 0 = slept extremely well and 10 = unable to sleep at all. A negative value indicates an improvement in pain score from baseline. The analyses were based on the change from baseline for the last assessment falling within the evaluable period (considered the end of treatment).
Population: The primary population for analysis was the full analysis set, which included all randomised subjects who received at least one dose of study medication and yielded on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 132 | -2.0 | 3.02 |
| Placebo | 142 | -1.6 | 2.76 |
The subject was to assess the change in their nerve pain due to diabetic neuropathy at the end of the study compared to baseline on a 7-point scale from very much worse to very much improved. The number of participants reporting each score is presented.
Population: The primary population for analysis was the full analysis set, which included all randomised subjects who received at least one dose of study medication and yielded on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 140 | 13 | - |
| Placebo | 141 | 14 | - |
| Sativex | 140 | 40 | - |
| Placebo | 141 | 36 | - |
| Sativex | 140 | 48 | - |
| Placebo | 141 | 35 | - |
| Sativex | 140 | 30 | - |
| Placebo | 141 | 45 | - |
| Sativex | 140 | 6 | - |
| Placebo | 141 | 9 | - |
| Sativex | 140 | 2 | - |
| Placebo | 141 | 2 | - |
| Sativex | 140 | 1 | - |
| Placebo | 141 | 0 | - |
The brief pain inventory (short form) 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 pain 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 analysis was the full analysis set, which included all randomised subjects who received at least one dose of study medication and yielded on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 137 | -1.2 | 1.92 |
| Placebo | 135 | -1.2 | 2.06 |
The EuroQol-5D Health Status Visual Analogue Scale rated the health state on a scale of 0-100 with 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 analysis was the full analysis set, which included all randomised subjects who received at least one dose of study medication and yielded on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 138 | 3.3 | 22.26 |
| Placebo | 135 | 7.8 | 22.91 |
The mean daily number of paracetamol tablets used were calculated for the periods over which the primary endpoint was calculated.
Population: The primary population for analysis was the full analysis set, which included all randomised subjects who received at least one dose of study medication and yielded on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 146 | -0.53 | 2.02 |
| Placebo | 148 | -0.35 | 1.94 |
The number of subjects who experienced an adverse event during the course of the study (including the follow-up period i.e 28 days after the end of treatment) is presented.
Population: The primary population for analysis was the full analysis set, which included all randomised subjects who received at least one dose of study medication and yielded on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 149 | 120 | - |
| Placebo | 148 | 101 | - |
| Sativex | 149 | 96 | - |
| Placebo | 148 | 52 | - |
Subjects rated their intoxication levels on a scale of 0-10, where 0 equals "no intoxication" and 10 equals "extreme intoxication". A negaitve value from baseline indicates and improvement. End of treatment was classed as the last on-treatment visit where data was recorded.
Population: The primary population for analysis was the full analysis set, which included all randomised subjects who received at least one dose of study medication and yielded on-treatment efficacy data.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 142 | 0.8 | 2.73 |
| Placebo | 145 | -0.3 | 1.96 |
A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS average pain score from baseline to week 14 (last 7 days). 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. The average pain NRS was completed at the same time each day, i.e. bedtime in the evening. Estimates were produced for a one-week period, with the evaluable period finishing at the end of the appropriate seven-day period.
Population: All subjects who were randomised and received at least one actuation of study medication were included in the analysis. Subjects with no data during the primary period (i.e. unknown response) were included in the analysis, and were classed as non-responders.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 149 | 54 | - |
| Placebo | 148 | 59 | - |
| Milestone | Sativex | Placebo |
|---|---|---|
| STARTED | 149 | 148 |
| COMPLETED | 105 | 125 |
| NOT COMPLETED | 44 | 23 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| ACUTE CORONARY SYNDROME | Cardiac disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| BRADYCARDIA | Cardiac disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| MYOCARDIAL INFARCTION | Cardiac disorders | Sativex: 1 / 149 · Placebo: 1 / 148 |
| EYE HAEMORRHAGE | Eye disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| GASTROINTESTINAL INFLAMMATION | Gastrointestinal disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| PERIODONTITIS | Gastrointestinal disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| ABDOMINAL PAIN | Gastrointestinal disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| GASTRITIS | Gastrointestinal disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| HAEMATEMESIS | Gastrointestinal disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| IMPAIRED GASTRIC EMPTYING | Gastrointestinal disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| NAUSEA | Gastrointestinal disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| VOMITING | Gastrointestinal disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| OEDEMA PERIPHERAL | General disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| PYREXIA | General disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| CELLULITIS | Infections and infestations | Sativex: 1 / 149 · Placebo: 0 / 148 |
| LOWER RESPIRATORY TRACT INFECTION | Infections and infestations | Sativex: 1 / 149 · Placebo: 0 / 148 |
| BLOOD GLUCOSE INCREASED | Investigations | Sativex: 0 / 149 · Placebo: 1 / 148 |
| DIABETIC KETOACIDOSIS | Metabolism and nutrition disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| HYPERGLYCAEMIA | Metabolism and nutrition disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| KETOACIDOSIS | Metabolism and nutrition disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| DIABETES MELLITUS INADEQUATE CONTROL | Metabolism and nutrition disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| BACK PAIN | Musculoskeletal and connective tissue disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| EXOSTOSIS | Musculoskeletal and connective tissue disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| MUSCULOSKELETAL CHEST PAIN | Musculoskeletal and connective tissue disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| RHABDOMYOLYSIS | Musculoskeletal and connective tissue disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| ISCHAEMIC STROKE | Nervous system disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| SYNCOPE | Nervous system disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| TRANSIENT ISCHAEMIC ATTACK | Nervous system disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| RENAL FAILURE | Renal and urinary disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| ESSENTIAL HYPERTENSION | Vascular disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| PERIPHERAL OCCLUSIVE DISEASE | Vascular disorders | Sativex: 1 / 149 · Placebo: 0 / 148 |
| ACCELERATED HYPERTENSION | Vascular disorders | Sativex: 0 / 149 · Placebo: 1 / 148 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Dizziness | Nervous system disorders | Sativex: 42 / 149 · Placebo: 7 / 148 |
| Somnolence | Nervous system disorders | Sativex: 11 / 149 · Placebo: 7 / 148 |
| Headache | Nervous system disorders | Sativex: 9 / 149 · Placebo: 11 / 148 |
| Lethargy | Nervous system disorders | Sativex: 5 / 149 · Placebo: 1 / 148 |
| Amnesia | Nervous system disorders | Sativex: 4 / 149 · Placebo: 2 / 148 |
| Dysgeusia | Nervous system disorders | Sativex: 4 / 149 · Placebo: 1 / 148 |
| Memory impairment | Nervous system disorders | Sativex: 4 / 149 · Placebo: 1 / 148 |
| Nausea | Gastrointestinal disorders | Sativex: 25 / 149 · Placebo: 15 / 148 |
| Vomiting | Gastrointestinal disorders | Sativex: 14 / 149 · Placebo: 11 / 148 |
| Dry mouth | Gastrointestinal disorders | Sativex: 12 / 149 · Placebo: 4 / 148 |
| Diarrhoea | Gastrointestinal disorders | Sativex: 10 / 149 · Placebo: 14 / 148 |
| Oral pain | Gastrointestinal disorders | Sativex: 7 / 149 · Placebo: 0 / 148 |
| Abdominal pain upper | Gastrointestinal disorders | Sativex: 5 / 149 · Placebo: 2 / 148 |
| Mouth ulceration | Gastrointestinal disorders | Sativex: 4 / 149 · Placebo: 2 / 148 |
| Oral discomfort | Gastrointestinal disorders | Sativex: 4 / 149 · Placebo: 4 / 148 |
| Fatigue | General disorders | Sativex: 10 / 149 · Placebo: 4 / 148 |
| Feeling abnormal | General disorders | Sativex: 4 / 149 · Placebo: 0 / 148 |
| Oedema peripheral | General disorders | Sativex: 4 / 149 · Placebo: 2 / 148 |
| Nasopharyngitis | Infections and infestations | Sativex: 8 / 149 · Placebo: 6 / 148 |
| Lower respiratory tract infection | Infections and infestations | Sativex: 6 / 149 · Placebo: 8 / 148 |
| Urinary tract infection | Infections and infestations | Sativex: 2 / 149 · Placebo: 8 / 148 |
| Disorientation | Psychiatric disorders |
Time frame: Day 0 and Day 98
The EuroQol-5D Health Status Visual Analogue Scale rated the health state on a scale of 0-100 with 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.
Time frame: Day 0 - Day 98
The mean daily number of paracetamol tablets used were calculated for the periods over which the primary endpoint was calculated.
Time frame: Day 0 - Day 133
The number of subjects who experienced an adverse event during the course of the study (including the follow-up period i.e 28 days after the end of treatment) is presented.
Time frame: Day 0 - Day 98
Subjects rated their intoxication levels on a scale of 0-10, where 0 equals "no intoxication" and 10 equals "extreme intoxication". A negaitve value from baseline indicates and improvement. End of treatment was classed as the last on-treatment visit where data was recorded.
| Sativex: 8 / 149 · Placebo: 1 / 148 |
| Depression | Psychiatric disorders | Sativex: 5 / 149 · Placebo: 2 / 148 |
| Insomnia | Psychiatric disorders | Sativex: 0 / 149 · Placebo: 4 / 148 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | Sativex: 4 / 149 · Placebo: 4 / 148 |
| Back pain | Musculoskeletal and connective tissue disorders | Sativex: 3 / 149 · Placebo: 5 / 148 |
| Arthralgia | Musculoskeletal and connective tissue disorders | Sativex: 2 / 149 · Placebo: 4 / 148 |
| Muscle spasms | Musculoskeletal and connective tissue disorders | Sativex: 2 / 149 · Placebo: 4 / 148 |
| Hypoglycaemia | Metabolism and nutrition disorders | Sativex: 9 / 149 · Placebo: 5 / 148 |
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | Sativex: 6 / 149 · Placebo: 4 / 148 |
| Cough | Respiratory, thoracic and mediastinal disorders | Sativex: 2 / 149 · Placebo: 4 / 148 |
| Pruritus | Skin and subcutaneous tissue disorders | Sativex: 1 / 149 · Placebo: 5 / 148 |
| Palpitations | Cardiac disorders | Sativex: 4 / 149 · Placebo: 1 / 148 |
| Vertigo | Ear and labyrinth disorders | Sativex: 6 / 149 · Placebo: 3 / 148 |