Trial Outcomes & Findings for A Study of Sativex® for Relief of Spasticity in Subjects With Multiple Sclerosis. (NCT NCT00711646)

Last Updated: 2023-05-06

Results Overview

The spasticity 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 average spasticity in the last 24 hours" where 0 = no spasticity and 10 = worst ever spasticity. For the analysis, end of treatment was defined as the mean of the last seven days in the study or the last three days if the subject withdrew due to worsening spasticity or lack of efficacy. A negative value indicates an improvement in spasticity score from baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

189 participants

Primary outcome timeframe

0-52 days

Results posted on

2023-05-06

Participant Flow

Participant milestones

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 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	124	65
Overall Study COMPLETED	112	62
Overall Study NOT COMPLETED	12	3

Reasons for withdrawal

Reasons for withdrawal
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 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	6	1
Overall Study Withdrawal by Subject	4	0
Overall Study Protocol Violation	0	1
Overall Study Lost to Follow-up	1	0
Overall Study administrative decision	0	1
Overall Study patient non-compliance	1	0

Baseline Characteristics

A Study of Sativex® for Relief of Spasticity in Subjects With Multiple Sclerosis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sativex n=124 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 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=65 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.	Total n=189 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	118 Participants n=5 Participants	65 Participants n=7 Participants	183 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants
Age, Continuous	49.7 years STANDARD_DEVIATION 10.2 • n=5 Participants	47.8 years STANDARD_DEVIATION 9.5 • n=7 Participants	49.1 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	34 Participants n=7 Participants	114 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	31 Participants n=7 Participants	75 Participants n=5 Participants
Region of Enrollment United Kingdom	108 participants n=5 Participants	56 participants n=7 Participants	164 participants n=5 Participants
Region of Enrollment Romania	16 participants n=5 Participants	9 participants n=7 Participants	25 participants n=5 Participants

PRIMARY outcome

Timeframe: 0-52 days

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

Outcome measures

Outcome measures
Measure	Sativex n=120 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 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=64 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Assessment of Change From Baseline in the Mean Spasticity 0-10 Numerical Rating Scale Score.	-1.18 units on a scale Standard Deviation 1.83	-0.63 units on a scale Standard Deviation 1.62

SECONDARY outcome

Timeframe: Days 0 - 52

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 mean Ashworth Scale score across muscle groups was calculated using only those muscle groups with a score of greater than or equal to two at baseline. All 20 muscle groups were assessed for spasticity (using a 1-5 scale): 1= no increase in muscle tone to 5= passive movement is difficult and affected part is rigid in flexion or extension. The score for all 20 muscle groups were added to give a total score out of 100; minimum score was 20. A decrease in score indicates an improvement in condition.

Outcome measures

Outcome measures
Measure	Sativex n=114 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 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=63 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in Mean Ashworth Scale Score at the End of Treatment	-0.64 units on a scale Standard Deviation 0.56	-0.53 units on a scale Standard Deviation 0.58

SECONDARY outcome

Timeframe: Days 0 - 52

Each day subjects recorded in their diary the frequency of their spasms using the following scoring system: 0 = no spasms, 1 = one or fewer spasms per day, 2 = between one and five spasms per day, 3 = six to nine spasms per day, 4 = ten or more spasms per day or continuous contraction. For the analysis, end of treatment was defined as the mean of the last seven days in the study or the last three days if the subject withdrew due to worsening spasticity or lack of efficacy.

Outcome measures

Outcome measures
Measure	Sativex n=120 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 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=64 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in Mean Spasm Frequency Score at the End of Treatment	-0.37 units on a scale Standard Deviation 0.77	-0.26 units on a scale Standard Deviation 0.74

SECONDARY outcome

Timeframe: Day 7 and 52

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

Arm - 3 movements were pinch grip, elbow flexion and shoulder abduction. The total arm score was the addition of the score for the 3 arm movements. One point was then added to give a maximum score of 100; minimum was 1 point. Where both arms were assessed, the average of the two limbs scores was used as the assessment score; otherwise the affected limb total score was used. An increase in score indicates an improvement in condition..

Outcome measures

Outcome measures
Measure	Sativex n=25 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 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=15 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in Mean Motricity Index Score for the Arms	3.64 units on a scale Standard Deviation 14.82	3.07 units on a scale Standard Deviation 10.08

SECONDARY outcome

Timeframe: Day 52

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

A 7-point Likert-type scale was used, with the question: 'Please assess the change in your condition since entry into the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their condition which was used at end of treatment to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.

Outcome measures

Outcome measures
Measure	Sativex n=124 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 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=65 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Patient's Global Impression of Change in Condition at the End of Treatment Very Much Improved	2 participants	0 participants
Patient's Global Impression of Change in Condition at the End of Treatment Much Improved	24 participants	11 participants
Patient's Global Impression of Change in Condition at the End of Treatment Minimally Improved	40 participants	20 participants
Patient's Global Impression of Change in Condition at the End of Treatment No Change	38 participants	26 participants
Patient's Global Impression of Change in Condition at the End of Treatment Minimally worse	10 participants	5 participants
Patient's Global Impression of Change in Condition at the End of Treatment Much Worse	2 participants	2 participants
Patient's Global Impression of Change in Condition at the End of Treatment Very Much Worse	0 participants	0 participants
Patient's Global Impression of Change in Condition at the End of Treatment Missing	8 participants	1 participants

SECONDARY outcome

Timeframe: Day 0-52

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

Outcome measures
Measure	Sativex n=124 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 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=65 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	102 participants	46 participants

SECONDARY outcome

Timeframe: Day 7 and Day 52

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

Ankle dorsiflexion, knee extension and hip flexion were assessed and scored to give a maximum of 100%. The Motricity Index score (scale 1-100) was recorded for limbs that had an associated Ashworth Scale score, which was greater than or equal to two at baseline.

Outcome measures

Outcome measures
Measure	Sativex n=103 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 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=56 Participants Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Change From Baseline in Mean Motricity Index Score for the Legs	6.01 units on a scale Standard Deviation 12.30	2.15 units on a scale Standard Deviation 13.41

Adverse Events

Sativex

Serious events: 4 serious events

Other events: 102 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sativex n=124 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 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=65 participants at risk Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Gastrointestinal disorders Vomiting NOS	0.81% 1/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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% 0/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Appendicitis	0.00% 0/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	1.5% 1/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Mobility Decreased	0.81% 1/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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% 0/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Bartholin's Abscess	0.81% 1/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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% 0/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Urinary Tract Infection NOS	1.6% 2/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	1.5% 1/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Lower Respiratory Tract Infection NOS	0.00% 0/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	1.5% 1/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Carcinoma NOS	0.81% 1/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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% 0/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.
Renal and urinary disorders Urinary Incontinence Aggravated	0.81% 1/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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% 0/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Pulmonary Embolism	0.00% 0/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	1.5% 1/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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

Additional Information

Mr Richard Potts, Clinical Operations Director

GW Pharma Ltd.

Phone: 0044 1223 266800

Email: [email protected]

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

Measure	Sativex n=124 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 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.	Placebo n=65 participants at risk Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Nervous system disorders Dizziness	32.3% 40/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	10.8% 7/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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	10.5% 13/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	6.2% 4/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Urinary Tract Infection NOS	10.5% 13/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	9.2% 6/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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	8.9% 11/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	6.2% 4/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Balance Impaired NOS	7.3% 9/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	1.5% 1/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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	7.3% 9/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	6.2% 4/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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	6.5% 8/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	6.2% 4/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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	5.6% 7/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	3.1% 2/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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	4.8% 6/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	10.8% 7/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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	4.8% 6/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	1.5% 1/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Confusion	4.8% 6/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	3.1% 2/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Depressed Mood	4.8% 6/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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% 0/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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	4.0% 5/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	1.5% 1/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Disorientation	4.0% 5/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	1.5% 1/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Dysgeusia	4.0% 5/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	1.5% 1/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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	3.2% 4/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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% 0/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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% 4/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	3.1% 2/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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% 4/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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% 0/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Weakness	3.2% 4/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	1.5% 1/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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 Pain in Limb	3.2% 4/124 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.	1.5% 1/65 • All adverse events occurring from the time of consent to post study follow up (9 - 10 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.