Trial Outcomes & Findings for A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia. (NCT NCT00711880)

NCT ID: NCT00711880

Last Updated: 2023-04-12

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 125 participants
• Primary outcome timeframe: Day 0 to Day 42
• Results posted on: 2023-04-12

Participant Flow

Participant milestones

Measure	Sativex Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Overall Study STARTED	63	62
Overall Study COMPLETED	50	55
Overall Study NOT COMPLETED	13	7

Reasons for withdrawal

Measure	Sativex Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Overall Study Adverse Event	11	2
Overall Study Patient non-compliance	1	0
Overall Study Lack of Efficacy	1	5

Baseline Characteristics

A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.

Baseline characteristics by cohort

Measure	Sativex n=63 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=62 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.	Total n=125 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	51 Participants n=5 Participants	49 Participants n=7 Participants	100 Participants n=5 Participants
Age, Categorical >=65 years	12 Participants n=5 Participants	13 Participants n=7 Participants	25 Participants n=5 Participants
Age, Continuous	52.4 years STANDARD_DEVIATION 15.8 • n=5 Participants	54.3 years STANDARD_DEVIATION 15.2 • n=7 Participants	53.4 years STANDARD_DEVIATION 15.4 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	39 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	23 Participants n=7 Participants	51 Participants n=5 Participants
Region of Enrollment United Kingdom	51 participants n=5 Participants	50 participants n=7 Participants	101 participants n=5 Participants
Region of Enrollment Belgium	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0 to Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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.

Outcome measures

Measure	Sativex n=61 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=62 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in the Mean Daily Peripheral Neuropathic Pain on a 0-10 Numerical Rating Scale Score During the Last Seven Days of Treatment (End of Treatment)	-1.57 units on a scale Standard Deviation 2.11	-0.59 units on a scale Standard Deviation 1.38

SECONDARY outcome

Timeframe: Day 0 to Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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.

Outcome measures

Measure	Sativex n=59 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=62 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in Mean Neuropathic Pain Scale Score at the End of Treatment	-9.7 units on a scale Standard Deviation 19.35	-2.0 units on a scale Standard Deviation 12.14

SECONDARY outcome

Timeframe: Day 7 - Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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.

Outcome measures

Measure	Sativex n=61 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=62 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in Mean Sleep Quality at the End of Treatment	-0.82 units on a scale Standard Deviation 0.76	-0.38 units on a scale Standard Deviation 0.68

SECONDARY outcome

Timeframe: Day 0 - Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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.

Outcome measures

Measure	Sativex n=53 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=57 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in the Mean Pain Disability Index Score at the End of Treatment	-5.6 units on a scale Standard Deviation 12.08	0.3 units on a scale Standard Deviation 8.71

SECONDARY outcome

Timeframe: Day 7 and Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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.

Outcome measures

Measure	Sativex n=55 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=51 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in Mean Dynamic Allodynia Test Score at the End of Treatment	-1.15 units on a scale Standard Deviation 2.23	-0.38 units on a scale Standard Deviation 1.72

SECONDARY outcome

Timeframe: Day 0 - Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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.

Outcome measures

Measure	Sativex n=56 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=62 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in Mean Static Allodynia Test Score at the End of Treatment	18.22 units on a scale Standard Deviation 50.20	2.84 units on a scale Standard Deviation 44.43

SECONDARY outcome

Timeframe: Day 7 and Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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.

Outcome measures

Measure	Sativex n=60 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=62 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in Mean Total General Health Questionnaire Score at the End of Treatment	-3.0 units on a scale Standard Deviation 7.93	-2.6 units on a scale Standard Deviation 5.72

SECONDARY outcome

Timeframe: Day 7 and Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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.

Outcome measures

Measure	Sativex n=40 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=42 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Selective Reminding' at the End of Treatment	0.53 units on a scale Standard Deviation 1.10	0.48 units on a scale Standard Deviation 1.27

SECONDARY outcome

Timeframe: Day 7 and Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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.

Outcome measures

Measure	Sativex n=39 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=42 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for '10/36 Spatial Recall' at the End of Treatment	0.79 units on a scale Standard Deviation 2.01	0.15 units on a scale Standard Deviation 2.12

SECONDARY outcome

Timeframe: Day 7 and Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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.

Outcome measures

Measure	Sativex n=39 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=42 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Symbol Digit Modalities' at the End of Treatment	1.6 units on a scale Standard Deviation 5.83	3.9 units on a scale Standard Deviation 7.38

SECONDARY outcome

Timeframe: Day 7 and Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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

Outcome measures

Measure	Sativex n=24 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=29 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Paced Auditory Serial Addition Task' at the End of Treatment	8.0 percentage of correct answers Standard Deviation 14.23	6.3 percentage of correct answers Standard Deviation 9.25

SECONDARY outcome

Timeframe: Day 7 and Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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).

Outcome measures

Measure	Sativex n=38 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=41 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Word List Generation' at the End of Treatment	3.5 number of words Standard Deviation 7.67	3.5 number of words Standard Deviation 8.47

SECONDARY outcome

Timeframe: Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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.

Outcome measures

Measure	Sativex n=63 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=62 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Subject Global Impression of Change in the Severity of Peripheral Neuropathic Pain at the End of Treatment Much Improved	11 participants	6 participants
Subject Global Impression of Change in the Severity of Peripheral Neuropathic Pain at the End of Treatment Minimally Improved	16 participants	6 participants
Subject Global Impression of Change in the Severity of Peripheral Neuropathic Pain at the End of Treatment Much Worse	4 participants	2 participants
Subject Global Impression of Change in the Severity of Peripheral Neuropathic Pain at the End of Treatment Very Much Worse	0 participants	0 participants
Subject Global Impression of Change in the Severity of Peripheral Neuropathic Pain at the End of Treatment Very Much Improved	5 participants	0 participants
Subject Global Impression of Change in the Severity of Peripheral Neuropathic Pain at the End of Treatment No Change	26 participants	46 participants
Subject Global Impression of Change in the Severity of Peripheral Neuropathic Pain at the End of Treatment Minimally Worse	0 participants	2 participants
Subject Global Impression of Change in the Severity of Peripheral Neuropathic Pain at the End of Treatment Missing	1 participants	0 participants

SECONDARY outcome

Timeframe: Day 0 - Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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.

Outcome measures

Measure	Sativex n=62 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=62 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Pre-dose in Mean Intoxication 100 mm Visual Analogue Scale Score at the End of Treatment	3.2 units on a scale Standard Deviation 11.39	1.4 units on a scale Standard Deviation 10.74

SECONDARY outcome

Timeframe: Day 0 - 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

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

Outcome measures

Measure	Sativex n=63 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=62 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Subject Global Impression of Change in the Severity of Allodynia in Their Chosen Allodynic Area at the End of Treatment Very Much Improved	3 participants	0 participants
Subject Global Impression of Change in the Severity of Allodynia in Their Chosen Allodynic Area at the End of Treatment Much Improved	12 participants	3 participants
Subject Global Impression of Change in the Severity of Allodynia in Their Chosen Allodynic Area at the End of Treatment Minimally Improved	14 participants	8 participants
Subject Global Impression of Change in the Severity of Allodynia in Their Chosen Allodynic Area at the End of Treatment Missing	1 participants	0 participants
Subject Global Impression of Change in the Severity of Allodynia in Their Chosen Allodynic Area at the End of Treatment No Change	30 participants	47 participants
Subject Global Impression of Change in the Severity of Allodynia in Their Chosen Allodynic Area at the End of Treatment Minimally Worse	1 participants	2 participants
Subject Global Impression of Change in the Severity of Allodynia in Their Chosen Allodynic Area at the End of Treatment Much Worse	2 participants	2 participants
Subject Global Impression of Change in the Severity of Allodynia in Their Chosen Allodynic Area at the End of Treatment Very Much Worse	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 0 - Day 42

Population: All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis

The number of subjects who reported an adverse event during the course of the study is presented

Outcome measures

Measure	Sativex n=63 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=62 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Incidence of Adverse Events as a Measure of Subject Safety	57 participants	48 participants

Adverse Events

Sativex

Serious events: 1 serious events

Other events: 57 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sativex n=63 participants at risk Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=62 participants at risk Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
General disorders Fall	0.00% 0/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	1.6% 1/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Infections and infestations Bronchopneumonia	1.6% 1/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Transient ischaemic attack	1.6% 1/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Hypoaesthesia	0.00% 0/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Myelitis NOS	0.00% 0/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	1.6% 1/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.

Other adverse events

Measure	Sativex n=63 participants at risk Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml per 100 micro litre. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=62 participants at risk Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Nervous system disorders Dizziness	28.6% 18/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	14.5% 9/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Nausea	22.2% 14/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	11.3% 7/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Fatigue	20.6% 13/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	8.1% 5/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Dry Mouth	17.5% 11/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	4.8% 3/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Vomiting Not Otherwise Specified (NOS)	12.7% 8/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	4.8% 3/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Feeling drunk	9.5% 6/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Headache NOS	9.5% 6/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	14.5% 9/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Diarrhoea NOS	6.3% 4/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Infections and infestations Nasopharyngitis	6.3% 4/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	3.2% 2/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Metabolism and nutrition disorders Anorexia	6.3% 4/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Somnolence	6.3% 4/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Abdominal pain upper	4.8% 3/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Disturbance in attention	4.8% 3/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Memory impairment	4.8% 3/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Fall	0.00% 0/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	4.8% 3/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Hypoaesthesia	0.00% 0/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	4.8% 3/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Eye disorders Vision Blurred	3.2% 2/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Oral Pain	0.00% 0/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	3.2% 2/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Dyspepsia	0.00% 0/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	3.2% 2/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Lethargy	3.2% 2/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Malaise	3.2% 2/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Investigations Blood Glucose Increased	3.2% 2/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Investigations Blood Alkaline Phosphatase NOS Increased	0.00% 0/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	3.2% 2/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Metabolism and nutrition disorders Hunger	3.2% 2/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	3.2% 2/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Psychiatric disorders Agitation	3.2% 2/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Psychiatric disorders Euphoric Mood	3.2% 2/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.2% 2/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Respiratory, thoracic and mediastinal disorders Pharyngitis	3.2% 2/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	3.2% 2/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Constipation	3.2% 2/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	6.5% 4/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Application Site Burning	3.2% 2/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	6.5% 4/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Application Site Pain	6.3% 4/63 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	3.2% 2/62 • All adverse events occurring from the time of consent to post study follow up i.e.8 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.

Additional Information

Mr Richard Potts, Clinical Operations Director

GW Pharma Ltd

Phone: 0044 1223 266800

Email: rp@gwpharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee GW will coordinate the dissemination of data from this study and may solicit input and assistance from the principal investigator. All publications, for example manuscripts, abstracts, oral/slide presentations or book chapters based on this study, must be submitted to GW for corporate review before release.
• Publication restrictions are in place

Restriction type: OTHER