Trial Outcomes & Findings for A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain (NCT NCT00713817)

NCT ID: NCT00713817

Last Updated: 2023-05-03

Results Overview

The pain severity Numerical Rating Scale was complete 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 severity 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 neuropathic pain. A negative value indicates an improvement in pain score from baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 19 participants
• Primary outcome timeframe: Day 0-35
• Results posted on: 2023-05-03

Participant Flow

Participant milestones

Measure	Sativex Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 24 actuations (THC 64.8 mg:CBD 60 mg) in 24 hours.	Placebo Contains no active drug but colourants and excipients. The maximum permitted dose was 24 actuations in any 24 hour period.
Overall Study STARTED	10	9
Overall Study COMPLETED	10	9
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain

Baseline characteristics by cohort

Measure	Sativex n=10 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 24 actuations (THC 64.8 mg:CBD 60 mg) in 24 hours.	Placebo n=9 Participants Contains no active drug but colourants and excipients. The maximum permitted dose was 24 actuations in any 24 hour period.	Total n=19 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=93 Participants	8 Participants n=4 Participants	18 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Age, Continuous	51.7 years STANDARD_DEVIATION 4.69 • n=93 Participants	56.1 years STANDARD_DEVIATION 10.33 • n=4 Participants	53.8 years STANDARD_DEVIATION 7.98 • n=27 Participants
Sex: Female, Male Female	6 Participants n=93 Participants	4 Participants n=4 Participants	10 Participants n=27 Participants
Sex: Female, Male Male	4 Participants n=93 Participants	5 Participants n=4 Participants	9 Participants n=27 Participants
Region of Enrollment United Kingdom	2 participants n=93 Participants	2 participants n=4 Participants	4 participants n=27 Participants
Region of Enrollment Czech Republic	8 participants n=93 Participants	7 participants n=4 Participants	15 participants n=27 Participants

PRIMARY outcome

Timeframe: Day 0-35

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.

The pain severity Numerical Rating Scale was complete 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 severity 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 neuropathic pain. A negative value indicates an improvement in pain score from baseline.

Outcome measures

Measure	Sativex n=10 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 24 actuations (THC 64.8 mg:CBD 60 mg) in 24 hours.	Placebo n=9 Participants Contains no active drug but colourants and excipients. The maximum permitted dose was 24 actuations in any 24 hour period.
Change From Baseline in Mean Daily Pain Severity on a 0-10 Numerical Rating Scale Score at the End of Treatment (Average of Last 7 Days Treatment)	0.57 units on a scale Standard Deviation 1.06	-0.49 units on a scale Standard Deviation 2.32

SECONDARY outcome

Timeframe: Day 7 to 35

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.

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.

Outcome measures

Measure	Sativex n=10 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 24 actuations (THC 64.8 mg:CBD 60 mg) in 24 hours.	Placebo n=9 Participants Contains no active drug but colourants and excipients. The maximum permitted dose was 24 actuations in any 24 hour period.
Change From Baseline Neuropathic Pain Score at the End of Treatment	2.56 units on a scale Standard Deviation 5.57	-2.06 units on a scale Standard Deviation 9.87

SECONDARY outcome

Timeframe: Day 7 to time of last dose

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.

Treatment failure was defined as follows:

A. Premature termination of Part B (Randomised-Withdrawal) study medication. All subjects who did not complete at least 28 days on Part B (Randomised-Withdrawal) study medicationOr:

B. An increase in pain, i.e. the mean pain 0-10 Numerical Rating Scale over seven consecutive days after Part B (Randomised-Withdrawal) randomisation had increased by at least 20% from the Part B (Randomised-Withdrawal) randomised treatment baseline.

Outcome measures

Measure	Sativex n=10 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 24 actuations (THC 64.8 mg:CBD 60 mg) in 24 hours.	Placebo n=9 Participants Contains no active drug but colourants and excipients. The maximum permitted dose was 24 actuations in any 24 hour period.
Number of Subjects Who Failed Treatment at the End of the Treatment Period	5 participants	4 participants

SECONDARY outcome

Timeframe: Day 0-35

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.

The percentage change from baseline in mean 0-10 Numerical Rating Scale pain score was calculated. The percentage changes from baseline were classified and the number of subjects with 20% or greater loss of response to treatment (i.e. percent increase from baseline ≥ 20%) is presented.

Outcome measures

Measure	Sativex n=10 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 24 actuations (THC 64.8 mg:CBD 60 mg) in 24 hours.	Placebo n=9 Participants Contains no active drug but colourants and excipients. The maximum permitted dose was 24 actuations in any 24 hour period.
Number of Subjects With More Than a 20% Loss of Response at the End of Treatment	3 participants	2 participants

SECONDARY outcome

Timeframe: Day 0-35

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.

The sleep disruption 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 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=10 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 24 actuations (THC 64.8 mg:CBD 60 mg) in 24 hours.	Placebo n=9 Participants Contains no active drug but colourants and excipients. The maximum permitted dose was 24 actuations in any 24 hour period.
Change From Baseline in Sleep Disruption 0-10 Numerical Rating Scale Score at the End of Treatment (Average of Last 7 Days Treatment)	0.24 units on a scale Standard Deviation 1.58	0.12 units on a scale Standard Deviation 0.97

SECONDARY outcome

Timeframe: Day 7 to 35

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.

A 7-point Likert-type scale was used, with the question: 'Please assess the status of your nerve pain 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". The number of subjects wo reported an improvement is presented.

Outcome measures

Measure	Sativex n=10 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 24 actuations (THC 64.8 mg:CBD 60 mg) in 24 hours.	Placebo n=9 Participants Contains no active drug but colourants and excipients. The maximum permitted dose was 24 actuations in any 24 hour period.
Subject Global Impression of Change at the End of Treatment	5 participants	4 participants

SECONDARY outcome

Timeframe: Day 0 -35

Population: The safety analysis set comprised all subjects who received at least one dose of study medication.

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

Outcome measures

Measure	Sativex n=10 Participants Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 24 actuations (THC 64.8 mg:CBD 60 mg) in 24 hours.	Placebo n=9 Participants Contains no active drug but colourants and excipients. The maximum permitted dose was 24 actuations in any 24 hour period.
Incidence of Adverse Events as a Measure of Subject Safety	3 participants	2 participants

Adverse Events

Sativex

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Sativex n=10 participants at risk Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 24 actuations (THC 64.8 mg:CBD 60 mg) in 24 hours.	Placebo n=9 participants at risk Contains no active drug but colourants and excipients. The maximum permitted dose was 24 actuations in any 24 hour period.
Nervous system disorders Headache	20.0% 2/10 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/9 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Tremor	10.0% 1/10 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/9 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.
Skin and subcutaneous tissue disorders Hyperhidrosis	10.0% 1/10 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/9 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Fatigue	10.0% 1/10 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/9 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.
Psychiatric disorders Insomnia	10.0% 1/10 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/9 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.
Infections and infestations Onychomycosis	0.00% 0/10 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.	11.1% 1/9 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.
Musculoskeletal and connective tissue disorders Back pain	10.0% 1/10 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/9 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.
Musculoskeletal and connective tissue disorders Bone pain	10.0% 1/10 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/9 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.
Investigations Weight decreased	10.0% 1/10 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/9 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Stomach discomfort	0.00% 0/10 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.	11.1% 1/9 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.
Eye disorders Cataract	0.00% 0/10 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs occurring during the study were reported on the running logs at the back of the study case report form.	11.1% 1/9 • All adverse events (AEs) occurring from the time of consent to post study follow up (63 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected. All AEs 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