Long Term Safety of Sativex Oromucosal Spray (Sativex®; Nabiximols) as Adjunctive Therapy in Patients With Uncontrolled Persistent Chronic Cancer Related Pain

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01337089
• Collaborator: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Enrollment: 660
• Locations: 128
• Arm: 1
• Actual Duration (Months): 60.3
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was a six-month open-label extension (OLE) study to evaluate the safety of long-term nabiximols (Sativex®) therapy when used as an adjunctive treatment in participants with advanced cancer. The study provided continued availability of nabiximols to participants who completed a preceding Phase 3 study and new (de novo) participants.

Condition or Disease	Intervention/Treatment	Phase
Pain; Advanced Cancer	Drug: Nabiximols	Phase 3

Detailed Description

This was a 6-month, multicenter, non-comparative, OLE study to evaluate the safety of long-term nabiximols use as an adjunctive measure in participants with advanced cancer. The study provided continued availability of nabiximols to participants who completed a preceding double-blind phase 3 study and de novo participants. Consenting eligible participants entered the extension study (Day 1) on the same day as the "end of treatment" visit of a parent study or within 7 days of the "end of treatment" visit or on the day of the "safety follow-up visit" of the parent study. The "safety follow-up" visit of a parent study was performed on the same day as Day 1, if the participant did not enter the OLE study on the same day as the "end of treatment" visit of a parent study. De novo participants attended a screening visit 3 to 14 days prior to enrollment (Day 1). All participants commenced dosing on Day 1. Further study visits took place after 2 weeks (Day 15), and every 4 weeks thereafter until the end of treatment period on Day 183 or earlier if the participant withdrew from the study.

Treatment was started as a single spray in the evening on the first day (Day 1). Participants then gradually titrated by 1 additional spray per day to an individualized dose, balancing efficacy and tolerability. Participants had to complete titration within 14 days of their first dose of study drug and then continue at the same dose for the remainder of the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 660 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Non-comparative, Open-label Extension Study to Assess the Long Term Safety of Sativex® Oromucosal Spray (Sativex®; Nabiximols) as Adjunctive Therapy in Patients With Uncontrolled Persistent Chronic Cancer Related Pain
• Actual Study Start Date: Jan 19, 2011
• Actual Primary Completion Date: Jan 27, 2016
• Actual Study Completion Date: Jan 27, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Non-comparative, open-label Nabiximols Nabiximols was self-administered by participants as a 100 microliter (μL) oromucosal spray, in the morning and evening, up to a maximum of 10 sprays per day for 6 months. Nabiximols oromucosal spray contained delta-9-tetrahydrocannabinol (THC) (27 milligrams [mg]/milliliter [mL]):cannabidiol (CBD) (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.

Drug: Nabiximols; Other Names: Sativex®

Outcome Measures

Primary Outcome Measures

1. Percent Of Participants With Treatment-emergent Adverse Events [Baseline, Day 183]

   Treatment-emergent Adverse Events (TEAEs) were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) dictionary version 17.0. A TEAE is defined as an adverse event with an onset after the start of study drug treatment. The percent of participants who experienced one or more TEAEs is reported.

Secondary Outcome Measures

1. Change From Baseline In Mean NRS Average Pain During The Last Period [Baseline, Last Period (Days 156-183) or last 27 days of treatment]

   Participants indicated the level of pain experienced in the last 24 hours on an 11-point Numerical Rating Scale (NRS), where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine." Change in mean NRS average pain was calculated as: Last Period NRS average pain score - Baseline NRS average pain score. A negative value indicates an improvement in average pain score from Baseline.

2. Change From Baseline In Mean Sleep Disruption NRS During The Last Period [Baseline, Last Period (Days 156-183) or last 27 days of treatment]

   Participants indicated the level of sleep disruption experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "did not disrupt sleep" and a score of 10 indicated "completely disrupted (unable to sleep at all)." Change in mean sleep disruption NRS was calculated as: Last Period sleep disruption NRS score - Baseline sleep disruption NRS score. A negative value indicates an improvement in sleep disruption score from Baseline.

3. Patient Satisfaction Questionnaire At Last Visit (Up To Day 183) [Last Visit (up to Day 183)]

   The Patient Satisfaction Questionnaire (PSQ) was used to assess level of satisfaction of the participant with the study drug, with the markers "extremely satisfied, very satisfied, slightly satisfied, neutral, slightly dissatisfied, very dissatisfied, extremely dissatisfied". Last visit refers to the last visit that a participant completed the assessment.

4. Change From Baseline In NRS Constipation At Last Visit (Up To Day 183) [Baseline, Last Visit (up to Day 183)]

   Participants indicated level of constipation on an 11-point NRS, where a score of 0 was "no constipation", and 10 was "constipation as bad as you can imagine." Last visit refers to the last visit that a participant completed the assessment. Change in NRS constipation score was calculated as: Last Visit NRS constipation score - Baseline NRS constipation score. A negative value indicates improvement in condition from Baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant had completed the parent study within the last seven days

• Willing and able to give written informed consent

• Willing and able to comply with all study requirements

Exclusion Criteria:

• The participant was using cannabis or cannabinoid based medications, other than the parent study investigational medicinal product (IMP), and was unwilling to abstain for the duration of the study

• Any history or immediate family history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition

• Any known or suspected history of a substance abuse/dependence disorder (including opiate abuse/dependence prior to the diagnosis of cancer), current heavy alcohol consumption (more than 60 grams [g] of pure alcohol per day for men, and more than 40 g of pure alcohol per day for women), current use of an illicit drug or current non-prescribed use of any prescription drug

• Had poorly controlled epilepsy or recurrent seizures (for example, one or more seizure during the last year)

• Had experienced myocardial infarction or clinically significant cardiac dysfunction within the last 12 months or had a cardiac disorder that, in the opinion of the investigator would have put the participant at risk of a clinically significant arrhythmia or myocardial infarction

• Had significantly impaired renal function

• Had significantly impaired hepatic function at the "end of treatment" visit of the parent study

• Female participants of child-bearing potential and male participants whose partner was of child-bearing potential, unless willing to ensure that they or their partner used effective contraception, for example, oral contraception, double barrier, intra-uterine device, during the study and for 3 months thereafter (however, a male condom should not have been used in conjunction with a female condom as this may not have proven effective)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Phoenix	Arizona	United States	85018
2		Phoenix	Arizona	United States	85028
3		El Cajon	California	United States	92020
4		Gilroy	California	United States	95020
5		Glendale	California	United States	91204
6		Santa Rosa	California	United States	95403
7		Clearwater	Florida	United States	33756
8		Daytona Beach	Florida	United States	32117
9		Holiday	Florida	United States	34691
10		Jacksonville	Florida	United States	32257
11		Lynn Haven	Florida	United States	32444
12		Miami	Florida	United States	33136
13		Stuart	Florida	United States	34994
14		Tampa	Florida	United States	33609
15		Winter Park	Florida	United States	32789
16		Marietta	Georgia	United States	30060
17		Newnan	Georgia	United States	30265
18		Stockbridge	Georgia	United States	30281
19		Woodlawn	Illinois	United States	62898
20		Ashland	Kentucky	United States	41101
21		Bossier City	Louisiana	United States	71111
22		Shreveport	Louisiana	United States	71105
23		Saint Louis Park	Minnesota	United States	55426
24		Kansas City	Missouri	United States	64132
25		Missoula	Montana	United States	59802
26		Berlin	New Jersey	United States	08009
27		New York	New York	United States	10003
28		New York	New York	United States	10010
29		Flat Rock	North Carolina	United States	28731
30		Winston-Salem	North Carolina	United States	27103
31		Cleveland	Ohio	United States	44119
32		Philadelphia	Pennsylvania	United States	19146
33		Houston	Texas	United States	77089
34		Laredo	Texas	United States	78041
35		Salt Lake City	Utah	United States	84112
36		Salt Lake City	Utah	United States	84124
37		Lacey	Washington	United States	98503
38		Parkville		Australia	3050
39		Bruxelles		Belgium	1000
40		Gabrovo		Bulgaria	5300
41		Varna		Bulgaria	9010
42		Vratsa		Bulgaria	3000
43		Benešov		Czechia	25601
44		Jablonec Nad Nisou		Czechia	46601
45		Most		Czechia	434 64
46		Nová Ves Pod Pleší		Czechia	262 04
47		Ostrava		Czechia	708 52
48		Plzen		Czechia	304 60
49		Sokolov		Czechia	356 01
50		Teplice		Czechia	415 01
51		České Budějovice		Czechia	370 01
52		České Budějovice		Czechia	370 87
53		Berlin		Germany	10435
54		Frankfurt		Germany	60311
55		Jena		Germany	07747
56		Lunen		Germany	44534
57		Stadtroda		Germany	07646
58		Wetzlar		Germany	35578
59		Wiesbaden		Germany	65189
60		Deszk		Hungary	6772
61		Komarom		Hungary	2900
62		Miskolc		Hungary	3501
63		Nyíregyháza		Hungary	4412
64		Szekszard		Hungary	7100
65		Szikszo		Hungary	3800
66		Beer Sheva		Israel	84101
67		Haifa		Israel	31096
68		Ramat Gan		Israel	52621
69		Zerifin		Israel	60930
70		Garbagnate Milanese		Italy	20024
71		Piacenza		Italy	29100
72		Torino		Italy	10126
73		Riga		Latvia	1038
74		Rēzekne		Latvia	4600
75		Klaipeda		Lithuania	92288
76		Siauliai		Lithuania	76307
77		Vilnius		Lithuania	08660
78		Chihuahua		Mexico	31238
79		Distrito Federal		Mexico	10700
80		Białystok		Poland	15-250
81		Bielsko-Biala		Poland	43-300
82		Bydgoszcz		Poland	85-796
83		Czeladz		Poland	41-250
84		Częstochowa		Poland	42-200
85		Częstochowa		Poland	42-217
86		Działdowo		Poland	13-200
87		Gdansk		Poland	80-208
88		Gliwice		Poland	44-101
89		Klodzko		Poland	57-300
90		Opole		Poland	45-272
91		Ostrowiec Swietokrzyski		Poland	27-400
92		Poznan		Poland	61-245
93		Warszawa		Poland	02-781
94		Warszawa		Poland	02-793
95		Wloclawek		Poland	87-800
96		Ponce		Puerto Rico	00717
97		San Juan		Puerto Rico	00927
98		Baia Mare		Romania	430031
99		Baia Mare		Romania	430241
100		Braila		Romania	810325
101		Bucuresti		Romania	010976
102		Bucuresti		Romania	011461
103		Cluj-Napoca		Romania	400015
104		Constanţa		Romania	900591
105		Craiova		Romania	200385
106		Focsani		Romania	620165
107		Iaşi		Romania	700106
108		Oradea		Romania	410469
109		Satu Mare		Romania	440055
110		Sibiu		Romania	550245
111		Suceava		Romania	720237
112		Târgovişte		Romania	130095
113		Granada		Spain	18014
114		Taichung		Taiwan	404
115		Tainan City		Taiwan	73657
116		Bury Saint Edmunds		United Kingdom	IP33 2QZ
117		Bury		United Kingdom	BL9 7TD
118		Cheltenham		United Kingdom	GL53 0QJ
119		Crumpsall		United Kingdom	M8 5RB
120		Edinburgh		United Kingdom	EH4 2XR
121		Edinburgh		United Kingdom
122		Gorleston-on-Sea		United Kingdom	NR31 6LA
123		Leeds		United Kingdom	LS17 6QD
124		Manchester		United Kingdom	M20 4BX
125		Norwich		United Kingdom	NR4 7UY
126		Plymouth		United Kingdom	PL6 8DH
127		Weston-super-Mare		United Kingdom	BS23 4TQ
128		Withington		United Kingdom	M20 4BX

Sponsors and Collaborators

• Jazz Pharmaceuticals
• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01337089
• Other Study ID Numbers: GWCA0999; 2009-016529-32
• First Posted: Apr 18, 2011
• Last Update Posted: Apr 23, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by Jazz Pharmaceuticals: Cancer pain; Opioid therapy; Inadequate analgesia; Optimized chronic opioid therapy
• Additional relevant MeSH terms: Cancer Pain; Nabiximols

Study Results

Participant Flow

Recruitment Details	Participants enrolled in this study included those who had taken part in studies NCT01262651 (GWCA0958), NCT01361607 (GWCA0962), and NCT01424566 (GWCA1103) and who chose to continue treatment by enrolling in this study, as well as new (de novo) participants who met all inclusion criteria and did not meet any of the exclusion criteria.
Pre-assignment Detail	For the de novo participants enrolled in this study, a screening visit took place 3 to 14 days prior to enrollment.

Arm/Group Title	Nabiximols
Arm/Group Description	Nabiximols was self-administered by participants as a 100 microliter (μL) oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 6 months. Nabiximols oromucosal spray contained delta-9-tetrahydrocannabinol (THC) (27 milligram [mg]/milliliter [mL]):cannabidiol (CBD) (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
Period Title: Overall Study
STARTED	660
Received at Least 1 Dose of Study Drug	660
Safety Population	660
Efficacy Dataset	659
COMPLETED	256
NOT COMPLETED	404

Baseline Characteristics

Arm/Group Title	Nabiximols
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 6 months. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
Overall Participants	660
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.2 (11.1)
Sex: Female, Male (Count of Participants)
Female	313 47.4%
Male	347 52.6%

Outcome Measures

1. Primary Outcome

Title	Percent Of Participants With Treatment-emergent Adverse Events
Description	Treatment-emergent Adverse Events (TEAEs) were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) dictionary version 17.0. A TEAE is defined as an adverse event with an onset after the start of study drug treatment. The percent of participants who experienced one or more TEAEs is reported.
Time Frame	Baseline, Day 183

Outcome Measure Data

Analysis Population Description

The Safety Population included all participants receiving at least 1 dose of study drug.

Arm/Group Title	Nabiximols
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 6 months. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
Measure Participants	660
Number [percent of participants]	82.9 12.6%

2. Secondary Outcome

Title	Change From Baseline In Mean NRS Average Pain During The Last Period
Description	Participants indicated the level of pain experienced in the last 24 hours on an 11-point Numerical Rating Scale (NRS), where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine." Change in mean NRS average pain was calculated as: Last Period NRS average pain score - Baseline NRS average pain score. A negative value indicates an improvement in average pain score from Baseline.
Time Frame	Baseline, Last Period (Days 156-183) or last 27 days of treatment

Outcome Measure Data

Analysis Population Description

The Safety Population included all participants receiving at least 1 dose of study drug.

Arm/Group Title	Nabiximols
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 6 months. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
Measure Participants	634
Mean (Standard Deviation) [units on a scale]	0.0 (1.8)

3. Secondary Outcome

Title	Change From Baseline In Mean Sleep Disruption NRS During The Last Period
Description	Participants indicated the level of sleep disruption experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "did not disrupt sleep" and a score of 10 indicated "completely disrupted (unable to sleep at all)." Change in mean sleep disruption NRS was calculated as: Last Period sleep disruption NRS score - Baseline sleep disruption NRS score. A negative value indicates an improvement in sleep disruption score from Baseline.
Time Frame	Baseline, Last Period (Days 156-183) or last 27 days of treatment

Outcome Measure Data

Analysis Population Description

The Safety Population included all participants receiving at least 1 dose of study drug.

Arm/Group Title	Nabiximols
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 6 months. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
Measure Participants	634
Mean (Standard Deviation) [units on a scale]	0.1 (1.9)

4. Secondary Outcome

Title	Patient Satisfaction Questionnaire At Last Visit (Up To Day 183)
Description	The Patient Satisfaction Questionnaire (PSQ) was used to assess level of satisfaction of the participant with the study drug, with the markers "extremely satisfied, very satisfied, slightly satisfied, neutral, slightly dissatisfied, very dissatisfied, extremely dissatisfied". Last visit refers to the last visit that a participant completed the assessment.
Time Frame	Last Visit (up to Day 183)

Outcome Measure Data

Analysis Population Description

The Safety Population included all participants receiving at least 1 dose of study drug.

Arm/Group Title	Nabiximols
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 6 months. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
Measure Participants	618
Extremely Satisfied	56 8.5%
Very Satisfied	230 34.8%
Slightly Satisfied	185 28%
Neutral	82 12.4%
Slightly Dissatisfied	33 5%
Very Dissatisfied	22 3.3%
Extremely Dissatisfied	10 1.5%

5. Secondary Outcome

Title	Change From Baseline In NRS Constipation At Last Visit (Up To Day 183)
Description	Participants indicated level of constipation on an 11-point NRS, where a score of 0 was "no constipation", and 10 was "constipation as bad as you can imagine." Last visit refers to the last visit that a participant completed the assessment. Change in NRS constipation score was calculated as: Last Visit NRS constipation score - Baseline NRS constipation score. A negative value indicates improvement in condition from Baseline.
Time Frame	Baseline, Last Visit (up to Day 183)

Outcome Measure Data

Analysis Population Description

The Safety Population included all participants receiving at least 1 dose of study drug.

Arm/Group Title	Nabiximols
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 6 months. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
Measure Participants	619
Mean (Standard Deviation) [units on a scale]	-0.1 (2.5)

Adverse Events

Time Frame	Up to Day 197 post-enrollment
Arm/Group Title	Nabiximols
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 6 months. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
All Cause Mortality
	Nabiximols
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Nabiximols
	Affected / at Risk (%)	# Events
Total	301/660 (45.6%)
Blood and lymphatic system disorders
Anaemia	8/660 (1.2%)
Anaemia Of Malignant Disease	1/660 (0.2%)
Febrile Neutropenia	1/660 (0.2%)
Neutropenia	1/660 (0.2%)
Cardiac disorders
Angina Pectoris	1/660 (0.2%)
Atrial Fibrillation	1/660 (0.2%)
Cardiopulmonary Failure	1/660 (0.2%)
Myocardial Infarction	3/660 (0.5%)
Congenital, familial and genetic disorders
Pyloric Stenosis	1/660 (0.2%)
Ear and labyrinth disorders
Deafness Neurosensory	1/660 (0.2%)
Vertigo	1/660 (0.2%)
Endocrine disorders
Adrenal Insufficiency	1/660 (0.2%)
Eye disorders
Blindness	1/660 (0.2%)
Gastrointestinal disorders
Nausea	6/660 (0.9%)
Vomiting	7/660 (1.1%)
Abdominal Pain	4/660 (0.6%)
Abdominal Pain Upper	1/660 (0.2%)
Gastritis	1/660 (0.2%)
Gastritis Erosive	1/660 (0.2%)
Haematemesis	1/660 (0.2%)
Ileus	2/660 (0.3%)
Intestinal Obstruction	1/660 (0.2%)
Mechanical Ileus	1/660 (0.2%)
Proctalgia	1/660 (0.2%)
Small Intestinal Obstruction	2/660 (0.3%)
Tongue Haemorrhage	1/660 (0.2%)
General disorders
Chest Pain	4/660 (0.6%)
Device Occlusion	1/660 (0.2%)
General Physical Health Deterioration	1/660 (0.2%)
Local Swelling	1/660 (0.2%)
Pain	6/660 (0.9%)
Pyrexia	3/660 (0.5%)
Infections and infestations
Gastroenteritis	2/660 (0.3%)
Urinary Tract Infection	1/660 (0.2%)
Bacteraemia	1/660 (0.2%)
Bronchitis	1/660 (0.2%)
Catheter Site Infection	1/660 (0.2%)
Cellulitis	2/660 (0.3%)
Clostridium Difficile Colitis	1/660 (0.2%)
Diverticulitis	1/660 (0.2%)
Herpes Zoster	1/660 (0.2%)
Klebsiella Sepsis	1/660 (0.2%)
Lobar Pneumonia	1/660 (0.2%)
Lower Respiratory Tract Infection	4/660 (0.6%)
Pelvic Abscess	1/660 (0.2%)
Pneumonia	6/660 (0.9%)
Pseudomembranous Colitis	1/660 (0.2%)
Respiratory Tract Infection	1/660 (0.2%)
Sepsis	3/660 (0.5%)
Sinusitis	1/660 (0.2%)
Staphylococcal Bacteraemia	1/660 (0.2%)
Staphylococcal Sepsis	1/660 (0.2%)
Subacute Endocarditis	1/660 (0.2%)
Viral Infection	1/660 (0.2%)
Injury, poisoning and procedural complications
Accidental Overdose	1/660 (0.2%)
Fall	5/660 (0.8%)
Femur Fracture	1/660 (0.2%)
Gastrointestinal Stoma Complication	1/660 (0.2%)
Joint Dislocation	1/660 (0.2%)
Procedural Headache	2/660 (0.3%)
Radiation Oesophagitis	1/660 (0.2%)
Shunt Occlusion	1/660 (0.2%)
Stoma Complication	1/660 (0.2%)
Metabolism and nutrition disorders
Cachexia	1/660 (0.2%)
Dehydration	4/660 (0.6%)
Diabetes Mellitus	1/660 (0.2%)
Hypokalaemia	1/660 (0.2%)
Hyponatraemia	1/660 (0.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/660 (0.2%)
Back Pain	2/660 (0.3%)
Muscular Weakness	1/660 (0.2%)
Osteonecrosis	1/660 (0.2%)
Pathological Fracture	4/660 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm Progression	209/660 (31.7%)
Breast Cancer Metastatic	1/660 (0.2%)
Cancer Pain	4/660 (0.6%)
Lung Adenocarcinoma	1/660 (0.2%)
Lung Neoplasm Malignant	1/660 (0.2%)
Metastases To Bone	1/660 (0.2%)
Metastases To Central Nervous System	3/660 (0.5%)
Metastases To Liver	1/660 (0.2%)
Metastases To Spine	1/660 (0.2%)
Metastatic Neoplasm	1/660 (0.2%)
Ovarian Cancer	1/313 (0.3%)
Plasma Cell Myeloma	2/660 (0.3%)
Squamous Cell Carcinoma Of Skin	1/660 (0.2%)
Tumour Haemorrhage	1/660 (0.2%)
Nervous system disorders
Spinal Cord Compression	3/660 (0.5%)
Altered State Of Consciousness	1/660 (0.2%)
Balance Disorder	1/660 (0.2%)
Carotid Artery Stenosis	1/660 (0.2%)
Cerebral Infarction	1/660 (0.2%)
Cerebrovascular Accident	3/660 (0.5%)
Grand Mal Convulsion	1/660 (0.2%)
Dementia With Lewy Bodies	1/660 (0.2%)
Dizziness	2/660 (0.3%)
Encephalopathy	1/660 (0.2%)
Epilepsy	1/660 (0.2%)
Posterior Reversible Encephalopathy Syndrome	2/660 (0.3%)
Syncope	1/660 (0.2%)
Tremor	1/660 (0.2%)
Convulsion	2/660 (0.3%)
Psychiatric disorders
Agitation	1/660 (0.2%)
Completed Suicide	1/660 (0.2%)
Depression	1/660 (0.2%)
Disorientation	4/660 (0.6%)
Mental Status Changes	2/660 (0.3%)
Suicide Attempt	1/660 (0.2%)
Renal and urinary disorders
Renal Failure Acute	1/660 (0.2%)
Urinary Retention	5/660 (0.8%)
Urinary Tract Obstruction	1/660 (0.2%)
Reproductive system and breast disorders
Genital Haemorrhage	1/660 (0.2%)
Vaginal Fistula	1/313 (0.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	5/660 (0.8%)
Chronic Obstructive Pulmonary Disease	3/660 (0.5%)
Hypoxia	1/660 (0.2%)
Pleural Effusion	2/660 (0.3%)
Pulmonary Embolism	1/660 (0.2%)
Respiratory Failure	3/660 (0.5%)
Skin and subcutaneous tissue disorders
Acute Febrile Neutrophilic Dermatosis	1/660 (0.2%)
Dry Gangrene	1/660 (0.2%)
Vascular disorders
Deep Vein Thrombosis	4/660 (0.6%)
Haemorrhage	1/660 (0.2%)
Hypertension	1/660 (0.2%)
Hypotension	1/660 (0.2%)
Inferior Vena Caval Occlusion	1/660 (0.2%)
Venous Thrombosis Limb	1/660 (0.2%)
Other (Not Including Serious) Adverse Events
	Nabiximols
	Affected / at Risk (%)	# Events
Total	291/660 (44.1%)
Blood and lymphatic system disorders
Anaemia	39/660 (5.9%)
Gastrointestinal disorders
Nausea	86/660 (13%)
Vomiting	59/660 (8.9%)
Constipation	44/660 (6.7%)
Diarrhoea	41/660 (6.2%)
General disorders
Fatigue	35/660 (5.3%)
Asthenia	50/660 (7.6%)
Metabolism and nutrition disorders
Decreased Appetite	49/660 (7.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm Progression	41/660 (6.2%)
Nervous system disorders
Dizziness	51/660 (7.7%)
Somnolence	38/660 (5.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	37/660 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.