Trial Outcomes & Findings for A Two-Part Study of Sativex® Oromucosal Spray for Relieving Uncontrolled Persistent Pain in Patients With Advanced Cancer (NCT NCT01424566)
NCT ID: NCT01424566
Last Updated: 2023-04-12
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
406 participants
Primary outcome timeframe
Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
Results posted on
2023-04-12
Participant Flow
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.
Participant milestones
| Measure |
Single-blind 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 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.
|
Double-blind Nabiximols
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).
|
Double-blind Placebo (GA-0034)
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).
|
|---|---|---|---|
|
Single-blind Treatment
STARTED
|
406
|
0
|
0
|
|
Single-blind Treatment
Received at Least 1 Dose of Study Drug
|
404
|
0
|
0
|
|
Single-blind Treatment
Single-blind Safety Population
|
404
|
0
|
0
|
|
Single-blind Treatment
Met Randomization Criteria
|
206
|
0
|
0
|
|
Single-blind Treatment
COMPLETED
|
206
|
0
|
0
|
|
Single-blind Treatment
NOT COMPLETED
|
200
|
0
|
0
|
|
Double-blind Treatment
STARTED
|
0
|
103
|
103
|
|
Double-blind Treatment
Received at Least 1 Dose of Study Drug
|
0
|
103
|
103
|
|
Double-blind Treatment
Randomized Safety Population
|
0
|
103
|
103
|
|
Double-blind Treatment
ITT Population
|
0
|
103
|
103
|
|
Double-blind Treatment
COMPLETED
|
0
|
78
|
88
|
|
Double-blind Treatment
NOT COMPLETED
|
0
|
25
|
15
|
Reasons for withdrawal
| Measure |
Single-blind 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 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.
|
Double-blind Nabiximols
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).
|
Double-blind Placebo (GA-0034)
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).
|
|---|---|---|---|
|
Single-blind Treatment
Adverse Event
|
71
|
0
|
0
|
|
Single-blind Treatment
Withdrawal by Subject
|
16
|
0
|
0
|
|
Single-blind Treatment
Withdrawal by Investigator
|
2
|
0
|
0
|
|
Single-blind Treatment
Did Not Meet Inclusion Criteria
|
108
|
0
|
0
|
|
Single-blind Treatment
Met Exclusion Criteria
|
1
|
0
|
0
|
|
Single-blind Treatment
Did Not Administer Any Study Drug
|
2
|
0
|
0
|
|
Double-blind Treatment
Adverse Event
|
0
|
21
|
13
|
|
Double-blind Treatment
Withdrawal by Subject
|
0
|
2
|
0
|
|
Double-blind Treatment
Withdrawal by Investigator
|
0
|
1
|
1
|
|
Double-blind Treatment
Lack of Efficacy
|
0
|
1
|
1
|
Baseline Characteristics
A Two-Part Study of Sativex® Oromucosal Spray for Relieving Uncontrolled Persistent Pain in Patients With Advanced Cancer
Baseline characteristics by cohort
| Measure |
Single-blind Nabiximols
n=406 Participants
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.
|
|---|---|
|
Age, Continuous
|
61.2 years
STANDARD_DEVIATION 11.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
177 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
229 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)Population: 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.
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.
Outcome measures
| Measure |
Double-blind Nabiximols
n=103 Participants
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).
|
Double-blind Placebo (GA-0034)
n=103 Participants
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).
|
|---|---|---|
|
Change From Randomization Baseline In Mean NRS Average Pain At End Of Treatment
|
0.5 units on a scale
Standard Deviation 1.3
|
0.5 units on a scale
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: Eligibility Baseline, End of Treatment (Day 36 of the double-blind period)Population: 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.
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.
Outcome measures
| Measure |
Double-blind Nabiximols
n=103 Participants
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).
|
Double-blind Placebo (GA-0034)
n=103 Participants
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).
|
|---|---|---|
|
Percent Improvement From Eligibility Baseline In Mean NRS Average Pain Score At End Of Treatment
|
33.3 percent improvement
Interval 18.2 to 51.8
|
35.7 percent improvement
Interval 18.8 to 51.3
|
SECONDARY outcome
Timeframe: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)Population: 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.
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.
Outcome measures
| Measure |
Double-blind Nabiximols
n=103 Participants
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).
|
Double-blind Placebo (GA-0034)
n=103 Participants
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).
|
|---|---|---|
|
Change From Randomization Baseline In Mean NRS Worst Pain At End Of Treatment
|
0.2 units on a scale
Standard Deviation 1.4
|
0.5 units on a scale
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)Population: 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.
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.
Outcome measures
| Measure |
Double-blind Nabiximols
n=103 Participants
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).
|
Double-blind Placebo (GA-0034)
n=103 Participants
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).
|
|---|---|---|
|
Change From Randomization Baseline In Mean Sleep Disruption NRS At End Of Treatment
|
0.2 units on a scale
Standard Deviation 1.3
|
0.5 units on a scale
Standard Deviation 1.4
|
SECONDARY outcome
Timeframe: Last Visit (up to Day 36 of the double-blind period)Population: 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.
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.
Outcome measures
| Measure |
Double-blind Nabiximols
n=88 Participants
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).
|
Double-blind Placebo (GA-0034)
n=97 Participants
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).
|
|---|---|---|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Very Much Improved
|
6 Participants
|
6 Participants
|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Much Improved
|
28 Participants
|
35 Participants
|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Slightly Improved
|
35 Participants
|
26 Participants
|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
No Change
|
8 Participants
|
15 Participants
|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Slightly Worse
|
8 Participants
|
8 Participants
|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Much Worse
|
3 Participants
|
6 Participants
|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Very Much Worse
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Last Visit (up to Day 36 of the double-blind period)Population: 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.
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.
Outcome measures
| Measure |
Double-blind Nabiximols
n=90 Participants
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).
|
Double-blind Placebo (GA-0034)
n=97 Participants
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).
|
|---|---|---|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Very Much Improved
|
7 Participants
|
7 Participants
|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Much Improved
|
22 Participants
|
30 Participants
|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Slightly Improved
|
37 Participants
|
25 Participants
|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
No Change
|
11 Participants
|
20 Participants
|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Slightly Worse
|
4 Participants
|
12 Participants
|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Much Worse
|
8 Participants
|
3 Participants
|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Very Much Worse
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Last Visit (up to Day 36 of the double-blind period)Population: 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.
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.
Outcome measures
| Measure |
Double-blind Nabiximols
n=89 Participants
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).
|
Double-blind Placebo (GA-0034)
n=97 Participants
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).
|
|---|---|---|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36 Of The Double-blind Period)
Extremely Satisfied
|
5 Participants
|
5 Participants
|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36 Of The Double-blind Period)
Very Satisfied
|
30 Participants
|
38 Participants
|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36 Of The Double-blind Period)
Slightly Satisfied
|
35 Participants
|
28 Participants
|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36 Of The Double-blind Period)
Neutral
|
14 Participants
|
10 Participants
|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36 Of The Double-blind Period)
Slightly Dissatisfied
|
2 Participants
|
11 Participants
|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36 Of The Double-blind Period)
Very Dissatisfied
|
0 Participants
|
4 Participants
|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36 Of The Double-blind Period)
Extremely Dissatisfied
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)Population: 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.
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.
Outcome measures
| Measure |
Double-blind Nabiximols
n=103 Participants
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).
|
Double-blind Placebo (GA-0034)
n=103 Participants
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).
|
|---|---|---|
|
Change From Randomization Baseline In Daily Total Opioid Use (Morphine Equivalent) At End Of Treatment
|
9.0 mg (morphine equivalent)
Standard Deviation 45.6
|
15.5 mg (morphine equivalent)
Standard Deviation 75.9
|
SECONDARY outcome
Timeframe: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)Population: 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.
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.
Outcome measures
| Measure |
Double-blind Nabiximols
n=103 Participants
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).
|
Double-blind Placebo (GA-0034)
n=103 Participants
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).
|
|---|---|---|
|
Change From Randomization Baseline In Daily Maintenance Opioid Dose (Morphine Equivalent) At End Of Treatment
|
0.0 mg (morphine equivalent)
Standard Deviation 11.0
|
8.5 mg (morphine equivalent)
Standard Deviation 54.6
|
SECONDARY outcome
Timeframe: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)Population: 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.
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.
Outcome measures
| Measure |
Double-blind Nabiximols
n=103 Participants
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).
|
Double-blind Placebo (GA-0034)
n=103 Participants
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).
|
|---|---|---|
|
Change From Randomization Baseline In Daily Break-through Opioid Dose (Morphine Equivalent) At End Of Treatment
|
9.0 mg (morphine equivalent)
Standard Deviation 50.7
|
7.0 mg (morphine equivalent)
Standard Deviation 36.1
|
SECONDARY outcome
Timeframe: Randomization Baseline, Last Visit (up to Day 36 of the double-blind period)Population: 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.
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.
Outcome measures
| Measure |
Double-blind Nabiximols
n=89 Participants
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).
|
Double-blind Placebo (GA-0034)
n=96 Participants
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).
|
|---|---|---|
|
Change From Randomization Baseline In NRS Constipation At Last Visit (Up To Day 36 Of The Double-blind Period)
|
0.0 units on a scale
Standard Deviation 1.8
|
-0.2 units on a scale
Standard Deviation 2.2
|
Adverse Events
Single-blind Nabiximols
Serious events: 80 serious events
Other events: 97 other events
Deaths: 0 deaths
Double-blind Nabiximols
Serious events: 33 serious events
Other events: 21 other events
Deaths: 0 deaths
Double-blind Placebo (GA-0034)
Serious events: 16 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Single-blind Nabiximols
n=404 participants at risk
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.
|
Double-blind Nabiximols
n=103 participants at risk
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).
|
Double-blind Placebo (GA-0034)
n=103 participants at risk
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).
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
1.9%
2/103 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Gastrointestinal disorders
Ascites
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Gastrointestinal disorders
Diarrhoea
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Gastrointestinal disorders
Gastrointestinal Haemorrhage
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Gastrointestinal disorders
Intestinal Obstruction
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Gastrointestinal disorders
Intestinal Perforation
|
0.50%
2/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Gastrointestinal disorders
Nausea
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Gastrointestinal disorders
Vomiting
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
General disorders
Breakthrough Pain
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
General disorders
General Physical Health Deterioration
|
0.50%
2/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
General disorders
Pain
|
0.50%
2/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
General disorders
Pyrexia
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Hepatobiliary disorders
Acute Hepatic Failure
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Infections and infestations
Cellulitis
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Infections and infestations
Lower Respiratory Tract Infection
|
0.50%
2/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Infections and infestations
Meningitis Listeria
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Infections and infestations
Pneumonia
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Infections and infestations
Pneumonia Bacterial
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Infections and infestations
Respiratory Tract Infection
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Infections and infestations
Sepsis
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Infections and infestations
Urinary Tract Infection
|
0.74%
3/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Investigations
ECG Signs of Myocardial Ischaemia
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain
|
0.99%
4/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to Central Nervous System
|
0.50%
2/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm Progression
|
10.1%
41/404 • Up to Day 43 of the double-blind period post-randomization
|
27.2%
28/103 • Up to Day 43 of the double-blind period post-randomization
|
10.7%
11/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Pain
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Nervous system disorders
Cerebrovascular Accident
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Nervous system disorders
Convulsion
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Nervous system disorders
Hypoglycaemic Coma
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Nervous system disorders
Nerve Root Compression
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Nervous system disorders
Sedation
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Nervous system disorders
Spinal Cord Compression
|
0.50%
2/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Renal and urinary disorders
Renal Failure Acute
|
0.50%
2/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.50%
2/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic Pain
|
0.25%
1/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Blood and lymphatic system disorders
Anaemia of Malignant Disease
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Gastrointestinal disorders
Duodenal Ulcer Haemorrhage
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Infections and infestations
Catheter Site Cellulitis
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Infections and infestations
Urosepsis
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Infections and infestations
Abdominal Sepsis
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Injury, poisoning and procedural complications
Foot Fracture
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Haemorrhage
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Vascular disorders
Peripheral Embolism
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
Other adverse events
| Measure |
Single-blind Nabiximols
n=404 participants at risk
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.
|
Double-blind Nabiximols
n=103 participants at risk
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).
|
Double-blind Placebo (GA-0034)
n=103 participants at risk
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).
|
|---|---|---|---|
|
Metabolism and nutrition disorders
Decreased Appetite
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
5.8%
6/103 • Up to Day 43 of the double-blind period post-randomization
|
2.9%
3/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Gastrointestinal disorders
Nausea
|
6.2%
25/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Gastrointestinal disorders
Vomiting
|
5.2%
21/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Nervous system disorders
Dizziness
|
6.7%
27/404 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
0.00%
0/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Nervous system disorders
Somnolence
|
11.4%
46/404 • Up to Day 43 of the double-blind period post-randomization
|
5.8%
6/103 • Up to Day 43 of the double-blind period post-randomization
|
0.97%
1/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
4.9%
5/103 • Up to Day 43 of the double-blind period post-randomization
|
5.8%
6/103 • Up to Day 43 of the double-blind period post-randomization
|
|
General disorders
Asthenia
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
5.8%
6/103 • Up to Day 43 of the double-blind period post-randomization
|
5.8%
6/103 • Up to Day 43 of the double-blind period post-randomization
|
|
Investigations
Weight Decreased
|
0.00%
0/404 • Up to Day 43 of the double-blind period post-randomization
|
6.8%
7/103 • Up to Day 43 of the double-blind period post-randomization
|
3.9%
4/103 • Up to Day 43 of the double-blind period post-randomization
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60