A Two-Part Study of Sativex® Oromucosal Spray for Relieving Uncontrolled Persistent Pain in Patients With Advanced Cancer

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01424566
• Collaborator: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Enrollment: 406
• Locations: 65
• Arms: 2
• Actual Duration (Months): 42
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study was to evaluate the efficacy of nabiximols (Sativex®), compared with placebo, when used as an adjunctive measure in relieving uncontrolled persistent chronic pain (not breakthrough pain) in participants with advanced cancer, who had inadequate analgesia even with optimized chronic opioid therapy.

This multi-center study was conducted in two parts. All participants enrolled into the trial received nabiximols during one of two parts of the study, but they did not know which part.

Eligible participants were not required to stop any of their current treatments or medications.

Condition or Disease	Intervention/Treatment	Phase
Pain; Advanced Cancer	Drug: Nabiximols; Drug: Placebo (GA-0034)	Phase 3

Detailed Description

This 11-week, multi-center, placebo-controlled study aimed to determine the efficacy, safety and tolerability of nabiximols administered as an adjunctive treatment for 5 weeks, versus placebo, assessed by a 2-part, randomized withdrawal design. The first part of the study (Part A) was single-blind (participants) and the second part of the study (Part B) was randomized, double-blind. Eligible participants had advanced cancer, with a clinical diagnosis of cancer related pain which was not wholly alleviated by their current optimized opioid treatment.

Qualifying participants entered the study at screening and commenced a 5- to 14-day eligibility period. During this period, eligible participants had 3 consecutive days where pain severity remained within defined parameters, break-through opioid usage had not exceeded an average of 4 episodes per day, and maintenance opioid medication and dose had not changed. Eligible participants underwent nabiximols titration during a single-blind treatment period lasting 10 days, followed by 4 days of therapy at the titrated dose. Participants who demonstrated an improvement of 15% or more on the score of the pain numerical rating scale were advanced to Part B, where they were randomized 1:1 to nabiximols or placebo in a double-blind fashion. Participants then received study treatments at their self-titrated doses for 5 weeks. After the end of the 5-week treatment period, participants were offered the option of entering an open-label extension (OLE) study; participants who entered the OLE up to 7 days after study completion had their follow-up assessments performed on the same day as their first OLE study visit. Participants that did not enter the OLE study had a safety follow up visit 14 days after treatment completion, which could be via telephone.

Study Design

• Study Type: Interventional
• Actual Enrollment: 406 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Two-part, Placebo-controlled, Study of the Safety and Efficacy of Sativex® Oromucosal Spray (Sativex®; Nabiximols) as Adjunctive Therapy in Relieving Uncontrolled Persistent Chronic Pain in Patients With Advanced Cancer, Who Have Inadequate Analgesia Even With Optimized Chronic Opioid Therapy.
• Actual Study Start Date: Jun 29, 2012
• Actual Primary Completion Date: Jul 10, 2015
• Actual Study Completion Date: Dec 28, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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 2 or 7 weeks. 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®
Placebo Comparator: Placebo (GA-0034) Placebo 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 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.	Drug: Placebo (GA-0034)

Outcome Measures

Primary Outcome Measures

1. Change From Randomization Baseline In Mean NRS Average Pain At End Of Treatment [Randomization Baseline, End of Treatment (Day 36 of the double-blind period)]

   Participants indicated the level of pain experienced in the last 24 hours on an 11-point 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: End of Treatment NRS average pain score - Randomization (Part B) Baseline NRS average pain score. The participant's Randomization (Part B) baseline pain 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in average pain score from Randomization (Part B) Baseline.

Secondary Outcome Measures

1. Percent Improvement From Eligibility Baseline In Mean NRS Average Pain Score At End Of Treatment [Eligibility Baseline, End of Treatment (Day 36 of the double-blind period)]

   Participants indicated level of pain in the last 24 hours on an 11-point NRS, where a score of 0 was "no pain" and 10 was "pain as bad as you can imagine". Eligibility Baseline = mean score from the 3-day eligibility period. End of Treatment = mean score over last (up to) 4 days to the final pain score at End of Treatment or up until Day 36 of the double-blind period, whichever is earlier, or final score available (prematurely terminated). Percentage improvement from baseline (Imp%) was calculated as: Imp% = (Eligibility Baseline pain NRS mean - End of Treatment pain NRS mean)/Eligibility Baseline pain NRS mean * 100. For participants who died or withdrew due to disease progression, Imp% values were used. For participants who died or withdrew unrelated to disease progression before end of Week 5, Imp% was zero for participants whose Imp% value was positive and it was Imp% for participants whose Imp% value was not positive.

2. Change From Randomization Baseline In Mean NRS Worst Pain At End Of Treatment [Randomization Baseline, End of Treatment (Day 36 of the double-blind period)]

   Participants indicated the level of worst pain experienced in the last 24 hours on an 11-point 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 worst pain was calculated as: End of Treatment NRS worst pain score - Randomization (Part B) Baseline NRS worst pain score. The participant's Randomization (Part B) baseline worst pain 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in worst pain score from Randomization (Part B) Baseline.

3. Change From Randomization Baseline In Mean Sleep Disruption NRS At End Of Treatment [Randomization Baseline, End of Treatment (Day 36 of the double-blind period)]

   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: End of Treatment sleep disruption NRS score - Randomization (Part B) Baseline sleep disruption NRS score. The participant's Randomization (Part B) baseline sleep disruption 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in sleep disruption score from Randomization (Part B) Baseline.

4. Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period) [Last Visit (up to Day 36 of the double-blind period)]

   The Subject Global Impression of Change (SGIC) was used to assess the overall status of the participant related to their cancer pain, with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse". The SGIC was assessed at Day 36 of the double-blind period or the day at which a participant's last evaluation was performed, such as in the case of early termination. Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36 of the double-blind period.

5. Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period) [Last Visit (up to Day 36 of the double-blind period)]

   The Physician Global Impression of Change (PGIC) was used by the treating physician (investigator/sub-investigator) to assess if there was any change in the general functional abilities of the participant since prior to commencement of study medication, with the markers: "very much worse, much worse, slightly worse, no change, slightly improved, much improved, very much improved". Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36 of the double-blind period.

6. Patient Satisfaction Questionnaire At Last Visit (Up To Day 36 Of The Double-blind Period) [Last Visit (up to Day 36 of the double-blind period)]

   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; this could be either Day 22 or Day 36 of the double-blind period.

7. Change From Randomization Baseline In Daily Total Opioid Use (Morphine Equivalent) At End Of Treatment [Randomization Baseline, End of Treatment (Day 36 of the double-blind period)]

   The total daily opioid use (in morphine equivalence) was the sum of morphine equivalence of daily maintenance dose and break-through dose. Change in daily total opioid use was calculated as: End of Treatment daily total opioid use - Randomization (Part B) Baseline daily total opioid use. The participant's Randomization (Part B) baseline daily total opioid use value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates a decrease in use from Randomization (Part B) Baseline.

8. Change From Randomization Baseline In Daily Maintenance Opioid Dose (Morphine Equivalent) At End Of Treatment [Randomization Baseline, End of Treatment (Day 36 of the double-blind period)]

   The prescribed daily quantity of opioid maintenance dose was calculated as the product of dose per use and daily frequency of use. Participants were asked: "Have you used your maintenance dose painkiller today as prescribed?" If the participant answered "No" to the question, the daily opioid maintenance dose usage on that day was set to 0. Change in daily maintenance opioid dose was calculated as: End of Treatment daily maintenance opioid dose - Randomization (Part B) Baseline daily maintenance opioid dose. The participant's Randomization (Part B) baseline daily maintenance opioid dose value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates a decrease in dose from Randomization (Part B) Baseline.

9. Change From Randomization Baseline In Daily Break-through Opioid Dose (Morphine Equivalent) At End Of Treatment [Randomization Baseline, End of Treatment (Day 36 of the double-blind period)]

   Daily break-through opioid dose usage was calculated as the product of prescribed dose per use, and the number of uses per day. If participants took more than 1 different break-through opioid for more than 1 day, the sum of morphine equivalence dose usages for each break-through opioid was calculated for the summary. Change in daily break-through opioid dose was calculated as: End of Treatment daily break-through opioid dose - Randomization (Part B) Baseline daily maintenance opioid dose. The participant's Randomization (Part B) baseline daily break-through opioid dose value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates a decrease in dose from Randomization (Part B) Baseline.

10. Change From Randomization Baseline In NRS Constipation At Last Visit (Up To Day 36 Of The Double-blind Period) [Randomization Baseline, Last Visit (up to Day 36 of the double-blind period)]

    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 - Randomization (Part B) Baseline NRS constipation score. The participant's Randomization (Part B) baseline constipation NRS value was the last evaluation (including unscheduled visits) in the single-blind treatment period (Part A) prior to the first dose of study drug in the double-blind treatment period (Part B). A negative value indicates improvement in condition from Randomization (Part B) Baseline.

Eligibility Criteria

Criteria

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

Inclusion Criteria (abbreviated):

• The participant had advanced cancer for which there is no known curative therapy

• The participant had a clinical diagnosis of cancer related pain, which was not alleviated with their current optimized opioid treatment

• The participant received an optimized maintenance dose of Step 3 opioid therapy, preferably with a sustained release preparation, but also allowing a regular maintenance dose of around the clock use of immediate release preparations

• The participant received a daily maintenance dose Step 3 opioid therapy of less than or equal to a total daily opioid dose of 500 mg/day of morphine equivalence (including maintenance and break-through opioids)

• The participant was using no more than one type of break-through opioid analgesia

Exclusion Criteria (abbreviated):

• Had any planned clinical interventions that would have affected their pain (for example, chemotherapy or radiation therapy where, in the clinical judgment of the investigator, these would be expected to affect pain)

• The participant was currently using or had used cannabis or cannabinoid-based medications within 30 days of study entry and was unwilling to abstain for the duration of the study

• 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

• 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 three months thereafter (however, a male condom was not to be 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		East Melbourne		Australia	3002
2		Parkville		Australia	3050
3		Shumen		Bulgaria	9700
4		Varna		Bulgaria	9010
5		Vratsa		Bulgaria	3000
6		Lunen		Germany	44534
7		Stadtroda		Germany	07646
8		Wetzlar		Germany	35578
9		Budapest		Hungary	1135
10		Deszk		Hungary	6772
11		Komárom		Hungary	2900
12		Nyíregyháza		Hungary	4412
13		Szikszó		Hungary	3800
14		Bangalore		India	560034
15		Jaipur		India	302017
16		Pune		India	411004
17		Ashkelon		Israel	78306
18		Beer Sheva		Israel	84101
19		Haifa		Israel	31096
20		Jerusalem		Israel	91120
21		Ramat Gan		Israel	52621
22		Zerifin		Israel	60930
23		Garbagnate Milanese		Italy	20024
24		Piacenza		Italy	29100
25		Torino		Italy	10126
26		Klaipeda		Lithuania	92288
27		Siauliai		Lithuania	76307
28		Vilnius		Lithuania	08660
29		Bydgoszcz		Poland	85-796
30		Czeladź		Poland	41-250
31		Gdansk		Poland	80-208
32		Gliwice		Poland	44-101
33		Klodzko		Poland	57-300
34		Opole		Poland	45-272
35		Ostrowiec Swietokrzyski		Poland	27-400
36		Poznan		Poland	61-245
37		Warszawa		Poland	02-781
38		Warszawa		Poland	02-793
39		Wloclawek		Poland	87-800
40		Alba Iulia		Romania	510077
41		Baia Mare		Romania	430241
42		Braila		Romania	810325
43		Bucuresti		Romania	010976
44		Focșani		Romania	620165
45		Oradea		Romania	410469
46		Satu Mare		Romania	440055
47		Sibiu		Romania	550245
48		Suceava		Romania	720237
49		Cadiz		Spain	11009
50		Granada		Spain	18014
51		Madrid		Spain	28050
52		Salamanca		Spain	37129
53		Sevilla		Spain	41013
54		Changhua City		Taiwan	500
55		Taichung		Taiwan	404
56		Tainan City		Taiwan	73657
57		Taipei		Taiwan	10002
58		Taipei		Taiwan	10099
59		Taipei		Taiwan	11213
60		Taipei		Taiwan	11490
61		Bury Saint Edmunds		United Kingdom	IP33 2QZ
62		Edinburgh		United Kingdom	EH4 2XR
63		Glasgow		United Kingdom	G12 0YN
64		Manchester		United Kingdom	M20 4BX
65		Norwich		United Kingdom	NR4 7UY

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Fallon MT, Albert Lux E, McQuade R, Rossetti S, Sanchez R, Sun W, Wright S, Lichtman AH, Kornyeyeva E. Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies. Br J Pain. 2017 Aug;11(3):119-133. doi: 10.1177/2049463717710042. Epub 2017 May 17.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01424566
• Other Study ID Numbers: GWCA1103; 2010-022905-17
• First Posted: Aug 29, 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: Neoplasms; Nabiximols

Study Results

Participant Flow

Pre-assignment Detail	Per the Statistical Analyses Plan, all randomized participants who received at least 1 dose of study drug were analyzed in the Intent to Treat (ITT) population as per randomized treatment group. Participants were included and analyzed according to the treatment group they were randomized to.

Arm/Group Title	Single-blind Nabiximols	Double-blind Nabiximols	Double-blind Placebo (GA-0034)
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 2 weeks. 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 flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in Numerical Rating Scale (NRS) pain scores during the single-blind treatment period (Part A).	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
Period Title: Single-blind Treatment
STARTED	406	0	0
Received at Least 1 Dose of Study Drug	404	0	0
Single-blind Safety Population	404	0	0
Met Randomization Criteria	206	0	0
COMPLETED	206	0	0
NOT COMPLETED	200	0	0
Period Title: Single-blind Treatment
STARTED	0	103	103
Received at Least 1 Dose of Study Drug	0	103	103
Randomized Safety Population	0	103	103
ITT Population	0	103	103
COMPLETED	0	78	88
NOT COMPLETED	0	25	15

Baseline Characteristics

Arm/Group Title	Single-blind 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 2 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
Overall Participants	406
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.2 (11.2)
Sex: Female, Male (Count of Participants)
Female	177 43.6%
Male	229 56.4%

Outcome Measures

1. Primary Outcome

Title	Change From Randomization Baseline In Mean NRS Average Pain At End Of Treatment
Description	Participants indicated the level of pain experienced in the last 24 hours on an 11-point 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: End of Treatment NRS average pain score - Randomization (Part B) Baseline NRS average pain score. The participant's Randomization (Part B) baseline pain 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in average pain score from Randomization (Part B) Baseline.
Time Frame	Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Outcome Measure Data

Analysis Population Description

The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Arm/Group Title	Double-blind Nabiximols	Double-blind Placebo (GA-0034)
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
Measure Participants	103	103
Mean (Standard Deviation) [units on a scale]	0.5 (1.3)	0.5 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind Nabiximols, Double-blind Placebo (GA-0034)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9173
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.42 to 0.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent Improvement From Eligibility Baseline In Mean NRS Average Pain Score At End Of Treatment
Description	Participants indicated level of pain in the last 24 hours on an 11-point NRS, where a score of 0 was "no pain" and 10 was "pain as bad as you can imagine". Eligibility Baseline = mean score from the 3-day eligibility period. End of Treatment = mean score over last (up to) 4 days to the final pain score at End of Treatment or up until Day 36 of the double-blind period, whichever is earlier, or final score available (prematurely terminated). Percentage improvement from baseline (Imp%) was calculated as: Imp% = (Eligibility Baseline pain NRS mean - End of Treatment pain NRS mean)/Eligibility Baseline pain NRS mean * 100. For participants who died or withdrew due to disease progression, Imp% values were used. For participants who died or withdrew unrelated to disease progression before end of Week 5, Imp% was zero for participants whose Imp% value was positive and it was Imp% for participants whose Imp% value was not positive.
Time Frame	Eligibility Baseline, End of Treatment (Day 36 of the double-blind period)

Outcome Measure Data

Analysis Population Description

The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Arm/Group Title	Double-blind Nabiximols	Double-blind Placebo (GA-0034)
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
Measure Participants	103	103
Median (Inter-Quartile Range) [percent improvement]	33.3	35.7

3. Secondary Outcome

Title	Change From Randomization Baseline In Mean NRS Worst Pain At End Of Treatment
Description	Participants indicated the level of worst pain experienced in the last 24 hours on an 11-point 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 worst pain was calculated as: End of Treatment NRS worst pain score - Randomization (Part B) Baseline NRS worst pain score. The participant's Randomization (Part B) baseline worst pain 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in worst pain score from Randomization (Part B) Baseline.
Time Frame	Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Outcome Measure Data

Analysis Population Description

The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Arm/Group Title	Double-blind Nabiximols	Double-blind Placebo (GA-0034)
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
Measure Participants	103	103
Mean (Standard Deviation) [units on a scale]	0.2 (1.4)	0.5 (1.6)

4. Secondary Outcome

Title	Change From Randomization Baseline In Mean Sleep Disruption NRS At End Of Treatment
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: End of Treatment sleep disruption NRS score - Randomization (Part B) Baseline sleep disruption NRS score. The participant's Randomization (Part B) baseline sleep disruption 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in sleep disruption score from Randomization (Part B) Baseline.
Time Frame	Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Outcome Measure Data

Analysis Population Description

The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Arm/Group Title	Double-blind Nabiximols	Double-blind Placebo (GA-0034)
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
Measure Participants	103	103
Mean (Standard Deviation) [units on a scale]	0.2 (1.3)	0.5 (1.4)

5. Secondary Outcome

Title	Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Description	The Subject Global Impression of Change (SGIC) was used to assess the overall status of the participant related to their cancer pain, with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse". The SGIC was assessed at Day 36 of the double-blind period or the day at which a participant's last evaluation was performed, such as in the case of early termination. Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36 of the double-blind period.
Time Frame	Last Visit (up to Day 36 of the double-blind period)

Outcome Measure Data

Analysis Population Description

The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Arm/Group Title	Double-blind Nabiximols	Double-blind Placebo (GA-0034)
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
Measure Participants	88	97
Very Much Improved	6 1.5%	6 NaN
Much Improved	28 6.9%	35 NaN
Slightly Improved	35 8.6%	26 NaN
No Change	8 2%	15 NaN
Slightly Worse	8 2%	8 NaN
Much Worse	3 0.7%	6 NaN
Very Much Worse	0 0%	1 NaN

6. Secondary Outcome

Title	Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Description	The Physician Global Impression of Change (PGIC) was used by the treating physician (investigator/sub-investigator) to assess if there was any change in the general functional abilities of the participant since prior to commencement of study medication, with the markers: "very much worse, much worse, slightly worse, no change, slightly improved, much improved, very much improved". Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36 of the double-blind period.
Time Frame	Last Visit (up to Day 36 of the double-blind period)

Outcome Measure Data

Analysis Population Description

The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Arm/Group Title	Double-blind Nabiximols	Double-blind Placebo (GA-0034)
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
Measure Participants	90	97
Very Much Improved	7 1.7%	7 NaN
Much Improved	22 5.4%	30 NaN
Slightly Improved	37 9.1%	25 NaN
No Change	11 2.7%	20 NaN
Slightly Worse	4 1%	12 NaN
Much Worse	8 2%	3 NaN
Very Much Worse	1 0.2%	0 NaN

7. Secondary Outcome

Title	Patient Satisfaction Questionnaire At Last Visit (Up To Day 36 Of The Double-blind Period)
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; this could be either Day 22 or Day 36 of the double-blind period.
Time Frame	Last Visit (up to Day 36 of the double-blind period)

Outcome Measure Data

Analysis Population Description

The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Arm/Group Title	Double-blind Nabiximols	Double-blind Placebo (GA-0034)
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
Measure Participants	89	97
Extremely Satisfied	5 1.2%	5 NaN
Very Satisfied	30 7.4%	38 NaN
Slightly Satisfied	35 8.6%	28 NaN
Neutral	14 3.4%	10 NaN
Slightly Dissatisfied	2 0.5%	11 NaN
Very Dissatisfied	0 0%	4 NaN
Extremely Dissatisfied	3 0.7%	1 NaN

8. Secondary Outcome

Title	Change From Randomization Baseline In Daily Total Opioid Use (Morphine Equivalent) At End Of Treatment
Description	The total daily opioid use (in morphine equivalence) was the sum of morphine equivalence of daily maintenance dose and break-through dose. Change in daily total opioid use was calculated as: End of Treatment daily total opioid use - Randomization (Part B) Baseline daily total opioid use. The participant's Randomization (Part B) baseline daily total opioid use value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates a decrease in use from Randomization (Part B) Baseline.
Time Frame	Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Outcome Measure Data

Analysis Population Description

The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Arm/Group Title	Double-blind Nabiximols	Double-blind Placebo (GA-0034)
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
Measure Participants	103	103
Mean (Standard Deviation) [mg (morphine equivalent)]	9.0 (45.6)	15.5 (75.9)

9. Secondary Outcome

Title	Change From Randomization Baseline In Daily Maintenance Opioid Dose (Morphine Equivalent) At End Of Treatment
Description	The prescribed daily quantity of opioid maintenance dose was calculated as the product of dose per use and daily frequency of use. Participants were asked: "Have you used your maintenance dose painkiller today as prescribed?" If the participant answered "No" to the question, the daily opioid maintenance dose usage on that day was set to 0. Change in daily maintenance opioid dose was calculated as: End of Treatment daily maintenance opioid dose - Randomization (Part B) Baseline daily maintenance opioid dose. The participant's Randomization (Part B) baseline daily maintenance opioid dose value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates a decrease in dose from Randomization (Part B) Baseline.
Time Frame	Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Outcome Measure Data

Analysis Population Description

The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Arm/Group Title	Double-blind Nabiximols	Double-blind Placebo (GA-0034)
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
Measure Participants	103	103
Mean (Standard Deviation) [mg (morphine equivalent)]	0.0 (11.0)	8.5 (54.6)

10. Secondary Outcome

Title	Change From Randomization Baseline In Daily Break-through Opioid Dose (Morphine Equivalent) At End Of Treatment
Description	Daily break-through opioid dose usage was calculated as the product of prescribed dose per use, and the number of uses per day. If participants took more than 1 different break-through opioid for more than 1 day, the sum of morphine equivalence dose usages for each break-through opioid was calculated for the summary. Change in daily break-through opioid dose was calculated as: End of Treatment daily break-through opioid dose - Randomization (Part B) Baseline daily maintenance opioid dose. The participant's Randomization (Part B) baseline daily break-through opioid dose value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates a decrease in dose from Randomization (Part B) Baseline.
Time Frame	Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Outcome Measure Data

Analysis Population Description

The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Arm/Group Title	Double-blind Nabiximols	Double-blind Placebo (GA-0034)
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
Measure Participants	103	103
Mean (Standard Deviation) [mg (morphine equivalent)]	9.0 (50.7)	7.0 (36.1)

11. Secondary Outcome

Title	Change From Randomization Baseline In NRS Constipation At Last Visit (Up To Day 36 Of The Double-blind Period)
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 - Randomization (Part B) Baseline NRS constipation score. The participant's Randomization (Part B) baseline constipation NRS value was the last evaluation (including unscheduled visits) in the single-blind treatment period (Part A) prior to the first dose of study drug in the double-blind treatment period (Part B). A negative value indicates improvement in condition from Randomization (Part B) Baseline.
Time Frame	Randomization Baseline, Last Visit (up to Day 36 of the double-blind period)

Outcome Measure Data

Analysis Population Description

The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Arm/Group Title	Double-blind Nabiximols	Double-blind Placebo (GA-0034)
Arm/Group Description	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
Measure Participants	89	96
Mean (Standard Deviation) [units on a scale]	0.0 (1.8)	-0.2 (2.2)

Adverse Events

Time Frame	Up to Day 43 of the double-blind period post-randomization
Arm/Group Title	Single-blind Nabiximols		Double-blind Nabiximols		Double-blind Placebo (GA-0034)
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 2 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. Two participants did not receive study drug and are not included in the safety set.		Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).		Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening for 5 weeks, at the same level of dosing attained during the last 4 days of the single-blind period; however, the number of sprays could be decreased based upon tolerability throughout the study. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. To enter the double-blind treatment period (Part B), participants had to achieve at least a 15% improvement in NRS pain scores during the single-blind treatment period (Part A).
All Cause Mortality
	Single-blind Nabiximols		Double-blind Nabiximols		Double-blind Placebo (GA-0034)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Single-blind Nabiximols		Double-blind Nabiximols		Double-blind Placebo (GA-0034)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	80/404 (19.8%)		33/103 (32%)		16/103 (15.5%)
Blood and lymphatic system disorders
Anaemia	1/404 (0.2%)		2/103 (1.9%)		1/103 (1%)
Anaemia of Malignant Disease	0/404 (0%)		0/103 (0%)		1/103 (1%)
Gastrointestinal disorders
Ascites	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Diarrhoea	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Gastrointestinal Haemorrhage	1/404 (0.2%)		1/103 (1%)		0/103 (0%)
Intestinal Obstruction	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Intestinal Perforation	2/404 (0.5%)		0/103 (0%)		0/103 (0%)
Nausea	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Vomiting	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Duodenal Ulcer Haemorrhage	0/404 (0%)		0/103 (0%)		1/103 (1%)
Haematemesis	0/404 (0%)		0/103 (0%)		1/103 (1%)
General disorders
Breakthrough Pain	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
General Physical Health Deterioration	2/404 (0.5%)		0/103 (0%)		0/103 (0%)
Pain	2/404 (0.5%)		0/103 (0%)		0/103 (0%)
Pyrexia	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Hepatobiliary disorders
Acute Hepatic Failure	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Infections and infestations
Cellulitis	1/404 (0.2%)		0/103 (0%)		1/103 (1%)
Lower Respiratory Tract Infection	2/404 (0.5%)		0/103 (0%)		0/103 (0%)
Meningitis Listeria	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Pneumonia	1/404 (0.2%)		1/103 (1%)		0/103 (0%)
Pneumonia Bacterial	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Respiratory Tract Infection	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Sepsis	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Urinary Tract Infection	3/404 (0.7%)		0/103 (0%)		0/103 (0%)
Catheter Site Cellulitis	0/404 (0%)		1/103 (1%)		0/103 (0%)
Urosepsis	0/404 (0%)		1/103 (1%)		0/103 (0%)
Abdominal Sepsis	0/404 (0%)		0/103 (0%)		1/103 (1%)
Bronchopneumonia	0/404 (0%)		0/103 (0%)		1/103 (1%)
Injury, poisoning and procedural complications
Foot Fracture	0/404 (0%)		1/103 (1%)		0/103 (0%)
Investigations
ECG Signs of Myocardial Ischaemia	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Metabolism and nutrition disorders
Hypokalaemia	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Pain in Extremity	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain	4/404 (1%)		0/103 (0%)		0/103 (0%)
Metastases to Central Nervous System	2/404 (0.5%)		0/103 (0%)		0/103 (0%)
Neoplasm Progression	41/404 (10.1%)		28/103 (27.2%)		11/103 (10.7%)
Tumour Pain	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Tumour Haemorrhage	0/404 (0%)		0/103 (0%)		1/103 (1%)
Nervous system disorders
Cerebrovascular Accident	1/404 (0.2%)		1/103 (1%)		0/103 (0%)
Convulsion	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Hypoglycaemic Coma	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Nerve Root Compression	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Sedation	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Spinal Cord Compression	2/404 (0.5%)		0/103 (0%)		0/103 (0%)
Renal and urinary disorders
Renal Failure Acute	2/404 (0.5%)		0/103 (0%)		0/103 (0%)
Hydronephrosis	0/404 (0%)		1/103 (1%)		0/103 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Dyspnoea	2/404 (0.5%)		0/103 (0%)		0/103 (0%)
Pleuritic Pain	1/404 (0.2%)		0/103 (0%)		0/103 (0%)
Vascular disorders
Deep Vein Thrombosis	0/404 (0%)		1/103 (1%)		0/103 (0%)
Peripheral Embolism	0/404 (0%)		0/103 (0%)		1/103 (1%)
Other (Not Including Serious) Adverse Events
	Single-blind Nabiximols		Double-blind Nabiximols		Double-blind Placebo (GA-0034)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/404 (24%)		21/103 (20.4%)		17/103 (16.5%)
Blood and lymphatic system disorders
Anaemia	0/404 (0%)		5/103 (4.9%)		6/103 (5.8%)
Gastrointestinal disorders
Nausea	25/404 (6.2%)		0/103 (0%)		0/103 (0%)
Vomiting	21/404 (5.2%)		0/103 (0%)		0/103 (0%)
General disorders
Asthenia	0/404 (0%)		6/103 (5.8%)		6/103 (5.8%)
Investigations
Weight Decreased	0/404 (0%)		7/103 (6.8%)		4/103 (3.9%)
Metabolism and nutrition disorders
Decreased Appetite	0/404 (0%)		6/103 (5.8%)		3/103 (2.9%)
Nervous system disorders
Dizziness	27/404 (6.7%)		0/103 (0%)		0/103 (0%)
Somnolence	46/404 (11.4%)		6/103 (5.8%)		1/103 (1%)

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.