Trial Outcomes & Findings for Study to Compare the Safety and Tolerability of Sativex® in Patients With Cancer Related Pain (NCT NCT00675948)

NCT ID: NCT00675948

Last Updated: 2023-05-03

Results Overview

The number of subjects who experienced an adverse event in this study is presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

43 participants

Primary outcome timeframe

0 - 657 days

Results posted on

2023-05-03

Participant Flow

The first subject was recruited on the 30th April 2002

Participant milestones

Participant milestones
Measure	Sativex Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg THC and 2.5 mg CBD	THC Alone Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC
Overall Study STARTED	39	4
Overall Study COMPLETED	0	1
Overall Study NOT COMPLETED	39	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Sativex Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg THC and 2.5 mg CBD	THC Alone Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC
Overall Study Adverse Event	23	1
Overall Study Lack of Efficacy	3	0
Overall Study Withdrawal by Subject	7	0
Overall Study Lost to Follow-up	2	0
Overall Study Protocol Violation	1	0
Overall Study Pain under control	1	0
Overall Study Sponsor decision	0	1
Overall Study Patient died	1	0
Overall Study Patient unable to comply with diaries	1	0
Overall Study Patient feels unable to take medication	0	1

Baseline Characteristics

Study to Compare the Safety and Tolerability of Sativex® in Patients With Cancer Related Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sativex n=39 Participants Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg THC and 2.5 mg CBD	THC Alone n=4 Participants Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC	Total n=43 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=99 Participants	4 Participants n=107 Participants	33 Participants n=206 Participants
Age, Categorical >=65 years	10 Participants n=99 Participants	0 Participants n=107 Participants	10 Participants n=206 Participants
Age, Continuous	57.5 years STANDARD_DEVIATION 13.5 • n=99 Participants	58.6 years STANDARD_DEVIATION 6.28 • n=107 Participants	57.6 years STANDARD_DEVIATION 12.94 • n=206 Participants
Sex: Female, Male Female	16 Participants n=99 Participants	3 Participants n=107 Participants	19 Participants n=206 Participants
Sex: Female, Male Male	23 Participants n=99 Participants	1 Participants n=107 Participants	24 Participants n=206 Participants
Region of Enrollment United Kingdom	31 participants n=99 Participants	3 participants n=107 Participants	34 participants n=206 Participants
Region of Enrollment Belgium	8 participants n=99 Participants	1 participants n=107 Participants	9 participants n=206 Participants

PRIMARY outcome

Timeframe: 0 - 657 days

Population: All subjects who took at least one dose of study medication and yielded on-treatment efficacy data were classed as the safety population.

The number of subjects who experienced an adverse event in this study is presented.

Outcome measures

Outcome measures
Measure	Sativex n=39 Participants Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD)	THC Alone n=4 Participants Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC
The Incidence of Adverse Events as a Measure of Subject Safety	37 participants	4 participants

SECONDARY outcome

Timeframe: 0 - 657 days

Population: The efficacy analyses were conducted on data from all subjects who entered the study, who were randomised, who received at least one dose of study medication and who yielded on-treatment efficacy data

The Brief Pain Inventory (Short Form) is a 14-item questionnaire that asks subjects to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items (range 0-10). The minimum value is zero and maximum is 10. A negative value indicates an improvement in score from baseline. The end of treatment was classed as study completion or withdrawal, if this occurred sooner. Calculation of the mean Brief Pain Inventory (Short Form) score was only carried out when data was available for 10 or more subjects at the relevant study visits. As such, no mean scores were calculated for subjects taking THC alone.

Outcome measures

Outcome measures
Measure	Sativex n=17 Participants Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD)	THC Alone Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC
Change From Baseline in the Mean Brief Pain Inventory (Short Form) - Pain Severity Score at the End of Treatment	-0.53 units on a scale Standard Deviation 1.28	—

SECONDARY outcome

Timeframe: 0 - 657 days

Population: The efficacy analyses were conducted on data from all randomised subjects who received at least one dose of study medication and who yielded on-treatment efficacy data.

The EORTC Quality of Life-C30 Health Status visual analogue scale was a self-reported score where subjects rated their health state from: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score from baseline indicates an improvement in condition. The end of treatment was classed as study completion or withdrawal, if this occurred sooner. Calculation of mean EORTC Quality of Life-C30 Health Status scores was only produced when data was available for 10 or more subjects at the relevant study visits. As such, no mean scores were calculated for subjects taking THC alone.

Outcome measures

Outcome measures
Measure	Sativex n=17 Participants Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD)	THC Alone Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC
Change From Baseline in the Mean EORTC Quality of Life-C30 Questionnaire - Global Health Status Score at the End of Treatment	-2.0 units on a scale Standard Deviation 28.34	—

Adverse Events

Sativex

Serious events: 20 serious events

Other events: 37 other events

Deaths: 0 deaths

THC Alone

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Mr Richard Potts, Clinical Operations Director

GW Pharma LTD.

Phone: 00 44 1223 266 800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publication Policy: 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

Serious adverse events
Measure	Sativex n=39 participants at risk Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg THC and 2.5 mg CBD	THC Alone n=4 participants at risk Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC
Blood and lymphatic system disorders Anaemia NOS aggravated	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Cardiac disorders Atrial fibrillation	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Haematemesis	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Diarrhoea NOS	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Intestinal obstruction NOS	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Nausea	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Vomiting NOS	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 General physical health deterioration	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Weakness	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Pneumonia	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Pyelonephritis NOS	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Sepsis NOS	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Urinary tract infection NOS	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Injury, poisoning and procedural complications Accident NOS	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Blood creatinine increased	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Blood potassium increased	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Blood urea increased	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Gamma-glutamyltransferase increased	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Metabolism and nutrition disorders Dehydration	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Pain in limb	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	20.5% 8/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to brain	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer NOS	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Loss of consciousness	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Neuropathic pain	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Somnolence	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Confusion	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Renal and urinary disorders Dysuria	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Renal and urinary disorders Renal Failure NOS	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Renal and urinary disorders Urinary incontinence	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Renal and urinary disorders Urinary retention	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Respiratory, thoracic and mediastinal disorders Respiratory depression	2.6% 1/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.

Other adverse events
Measure	Sativex n=39 participants at risk Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg THC and 2.5 mg CBD	THC Alone n=4 participants at risk Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC
Gastrointestinal disorders Nausea	25.6% 10/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Vomiting	25.6% 10/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Dry mouth	12.8% 5/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Diarrhoea	10.3% 4/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Dizziness	20.5% 8/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Somnolence	20.5% 8/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Headache	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Memory impairment	0.00% 0/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Confusion	17.9% 7/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Pain in limb	20.5% 8/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Arthralgia	0.00% 0/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea NOS	7.7% 3/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Blood and lymphatic system disorders Anaemia	10.3% 4/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Hepatobiliary disorders Cholelithiasis	0.00% 0/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Cardiac disorders Atrial fibrillation	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Dyspepsia	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Gastritis NOS	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Haematemesis	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Thirst	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Weakness	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Lower respiratory tract infection NOS	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Oral candidiasis	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Cellulitis	0.00% 0/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Injury, poisoning and procedural complications Therapeutic agent toxicity	0.00% 0/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Liver function tests abnormal	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Metabolism and nutrition disorders Anorexia	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Pain in back	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Muscle spasms	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Peripheral swelling	0.00% 0/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	28.2% 11/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastasis to bone	0.00% 0/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Jerky movement	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Clonic convulsions	0.00% 0/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.	25.0% 1/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Anxiety	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Confusional state	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Depression	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Disorientation	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Hallucination NOS	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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 Affect lability	5.1% 2/39 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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% 0/4 • All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 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.