Trial Outcomes & Findings for Sativex® for Relieving Persistent Pain in Patients With Advanced Cancer (NCT NCT01361607)
NCT ID: NCT01361607
Last Updated: 2023-04-12
Results Overview
Participants indicated level of pain in the last 24 hours on an 11-point Numerical Rating Scale (NRS), where a score of 0 was "no pain" and 10 was "pain as bad as you can imagine". Baseline = mean score from first day of 3-day eligibility period through to the day before first dose of study drug. End of Treatment = mean score over last (up to) 7 days to the final pain score at End of Treatment or up until Day 35, whichever is earlier, or final score available (prematurely terminated). Percentage improvement from baseline (Imp%) was calculated as: Imp% = (Baseline pain NRS mean - End of Treatment pain NRS mean)/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 (no diary data from Day 33 onwards), Imp% was zero for participants whose Imp% value was positive and it was Imp% for participants whose Imp% value was not positive.
COMPLETED
PHASE3
399 participants
Baseline, End of Treatment (Day 36)
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. However, if a participant randomized to placebo ever took a nabiximols dose, the participant was analyzed as nabiximols-treated in the Safety population.
Participant milestones
| Measure |
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 5 weeks. Nabiximols oromucosal spray contained delta-9-tetrahydrocannabinol (THC) (27 milligram \[mg\]/milliliter \[mL\]):cannabidiol (CBD) (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
200
|
199
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
198
|
199
|
|
Overall Study
Safety Population
|
199
|
198
|
|
Overall Study
ITT Population
|
198
|
199
|
|
Overall Study
COMPLETED
|
136
|
158
|
|
Overall Study
NOT COMPLETED
|
64
|
41
|
Reasons for withdrawal
| Measure |
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 5 weeks. Nabiximols oromucosal spray contained delta-9-tetrahydrocannabinol (THC) (27 milligram \[mg\]/milliliter \[mL\]):cannabidiol (CBD) (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
38
|
29
|
|
Overall Study
Withdrawal by Subject
|
19
|
8
|
|
Overall Study
Withdrawal by Investigator
|
5
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Met Withdrawal Criteria
|
1
|
1
|
Baseline Characteristics
Sativex® for Relieving Persistent Pain in Patients With Advanced Cancer
Baseline characteristics by cohort
| Measure |
Nabiximols
n=200 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=199 Participants
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.
|
Total
n=399 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.0 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
59.6 years
STANDARD_DEVIATION 11.0 • n=7 Participants
|
59.8 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
94 Participants
n=5 Participants
|
102 Participants
n=7 Participants
|
196 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
106 Participants
n=5 Participants
|
97 Participants
n=7 Participants
|
203 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, End of Treatment (Day 36)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 Numerical Rating Scale (NRS), where a score of 0 was "no pain" and 10 was "pain as bad as you can imagine". Baseline = mean score from first day of 3-day eligibility period through to the day before first dose of study drug. End of Treatment = mean score over last (up to) 7 days to the final pain score at End of Treatment or up until Day 35, whichever is earlier, or final score available (prematurely terminated). Percentage improvement from baseline (Imp%) was calculated as: Imp% = (Baseline pain NRS mean - End of Treatment pain NRS mean)/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 (no diary data from Day 33 onwards), 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 |
Nabiximols
n=198 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=199 Participants
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.
|
|---|---|---|
|
Percent Improvement From Baseline In Mean NRS Average Pain At End Of Treatment
|
7.2 percent improvement
Interval 0.0 to 29.4
|
9.5 percent improvement
Interval 0.0 to 34.5
|
SECONDARY outcome
Timeframe: Baseline, End of Treatment (Day 36)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 - Baseline NRS average pain score. A negative value indicates an improvement in average pain score from Baseline.
Outcome measures
| Measure |
Nabiximols
n=198 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=199 Participants
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.
|
|---|---|---|
|
Change From Baseline In Mean NRS Average Pain At End Of Treatment
|
-0.9 units on a scale
Standard Deviation 1.5
|
-1.0 units on a scale
Standard Deviation 1.5
|
SECONDARY outcome
Timeframe: Baseline, End of Treatment (Day 36)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 - Baseline NRS worst pain score. A negative value indicates an improvement in worst pain score from Baseline.
Outcome measures
| Measure |
Nabiximols
n=198 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=199 Participants
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.
|
|---|---|---|
|
Change From Baseline In Mean NRS Worst Pain At End Of Treatment
|
-1.0 units on a scale
Standard Deviation 1.7
|
-1.2 units on a scale
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: Baseline, End of Treatment (Day 36)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 - Baseline sleep disruption NRS score. A negative value indicates an improvement in sleep disruption score from Baseline.
Outcome measures
| Measure |
Nabiximols
n=198 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=199 Participants
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.
|
|---|---|---|
|
Change From Baseline In Mean Sleep Disruption NRS At End Of Treatment
|
-0.9 units on a scale
Standard Deviation 1.8
|
-1.1 units on a scale
Standard Deviation 1.7
|
SECONDARY outcome
Timeframe: Last visit (up to Day 36)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 or 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.
Outcome measures
| Measure |
Nabiximols
n=175 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=184 Participants
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.
|
|---|---|---|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36)
Very Much Improved
|
19 Participants
|
11 Participants
|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36)
Much Improved
|
36 Participants
|
35 Participants
|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36)
Slightly Improved
|
64 Participants
|
51 Participants
|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36)
No Change
|
38 Participants
|
67 Participants
|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36)
Slightly Worse
|
13 Participants
|
13 Participants
|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36)
Much Worse
|
5 Participants
|
6 Participants
|
|
Subject Global Impression Of Change At Last Visit (Up To Day 36)
Very Much Worse
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Last Visit (up to Day 36)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.
Outcome measures
| Measure |
Nabiximols
n=176 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=184 Participants
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.
|
|---|---|---|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36)
Very Much Improved
|
13 Participants
|
11 Participants
|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36)
Much Improved
|
37 Participants
|
32 Participants
|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36)
Slightly Improved
|
62 Participants
|
48 Participants
|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36)
No Change
|
41 Participants
|
78 Participants
|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36)
Slightly Worse
|
18 Participants
|
10 Participants
|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36)
Much Worse
|
5 Participants
|
4 Participants
|
|
Physician Global Impression Of Change At Last Visit (Up To Day 36)
Very Much Worse
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Last Visit (up to Day 36)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.
Outcome measures
| Measure |
Nabiximols
n=175 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=184 Participants
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.
|
|---|---|---|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36)
Extremely Satisfied
|
18 Participants
|
8 Participants
|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36)
Very Satisfied
|
34 Participants
|
43 Participants
|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36)
Slightly Satisfied
|
55 Participants
|
54 Participants
|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36)
Neutral
|
35 Participants
|
52 Participants
|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36)
Slightly Dissatisfied
|
13 Participants
|
15 Participants
|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36)
Very Dissatisfied
|
15 Participants
|
6 Participants
|
|
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36)
Extremely Dissatisfied
|
5 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Baseline, End of Treatment (Day 36)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 - Baseline daily total opioid use. A negative value indicates a decrease in use from Baseline.
Outcome measures
| Measure |
Nabiximols
n=198 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=199 Participants
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.
|
|---|---|---|
|
Change From Baseline In Daily Total Opioid Use (Morphine Equivalent) At End Of Treatment
|
-6.5 mg (morphine equivalent)
Standard Deviation 53.9
|
2.3 mg (morphine equivalent)
Standard Deviation 42.5
|
SECONDARY outcome
Timeframe: Baseline, End of Treatment (Day 36)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 - Baseline daily maintenance opioid dose. A negative value indicates a decrease in dose from Baseline.
Outcome measures
| Measure |
Nabiximols
n=197 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=199 Participants
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.
|
|---|---|---|
|
Change From Baseline In Daily Maintenance Opioid Dose (Morphine Equivalent) At End of Treatment
|
-1.5 mg (morphine equivalent)
Standard Deviation 38.2
|
1.9 mg (morphine equivalent)
Standard Deviation 34.3
|
SECONDARY outcome
Timeframe: Baseline, End of Treatment (Day 36)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 - Baseline daily break-through opioid dose. A negative value indicates a decrease in dose from Baseline.
Outcome measures
| Measure |
Nabiximols
n=198 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=199 Participants
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.
|
|---|---|---|
|
Change From Baseline In Daily Break-through Opioid Dose (Morphine Equivalent) At End Of Treatment
|
-4.4 mg (morphine equivalent)
Standard Deviation 27.7
|
0.5 mg (morphine equivalent)
Standard Deviation 20.5
|
SECONDARY outcome
Timeframe: Baseline, Last Visit (up to Day 36)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; this could be either Day 22 or Day 36. Change in NRS constipation score was calculated as: Last Visit NRS constipation score - Baseline NRS constipation score. A negative value indicates improvement in condition from Baseline.
Outcome measures
| Measure |
Nabiximols
n=174 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=184 Participants
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.
|
|---|---|---|
|
Change From Baseline In NRS Constipation At Last Visit (Up To Day 36)
|
-0.4 units on a scale
Standard Deviation 2.6
|
-0.6 units on a scale
Standard Deviation 2.7
|
Adverse Events
Nabiximols
Placebo (GA-0034)
Serious adverse events
| Measure |
Nabiximols
n=199 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=198 participants at risk
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.
|
|---|---|---|
|
Psychiatric disorders
Disorientation
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Vascular disorders
Hypotension
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Cardiac disorders
Cardiac Failure Congestive
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Cardiac disorders
Tachycardia
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Gastrointestinal disorders
Constipation
|
1.0%
2/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Gastrointestinal disorders
Vomiting
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
General disorders
Chest Pain
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
General disorders
Generalised Oedema
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Infections and infestations
Bronchitis
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Infections and infestations
Device Related Infection
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Infections and infestations
Device Related Sepsis
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Infections and infestations
Groin Abscess
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Infections and infestations
Helicobacter Gastritis
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Infections and infestations
Lobar Pneumonia
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Infections and infestations
Pneumonia
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Infections and infestations
Pseudomembranous Colitis
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Infections and infestations
Staphylococcal Sepsis
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Infections and infestations
Urinary Tract Infection
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Injury, poisoning and procedural complications
Fall
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Injury, poisoning and procedural complications
Post Procedural Haemorrhage
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Injury, poisoning and procedural complications
Wound Haemorrhage
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Metabolism and nutrition disorders
Cachexia
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Metabolism and nutrition disorders
Dehydration
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chondrosarcoma Metastatic
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal Cancer
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma Malignant
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm Progression
|
11.6%
23/199 • Up to Day 43 post-randomization
|
15.7%
31/198 • Up to Day 43 post-randomization
|
|
Nervous system disorders
Cerebrovascular Accident
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Nervous system disorders
Convulsion
|
0.00%
0/199 • Up to Day 43 post-randomization
|
0.51%
1/198 • Up to Day 43 post-randomization
|
|
Nervous system disorders
Somnolence
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
|
Psychiatric disorders
Anxiety
|
0.50%
1/199 • Up to Day 43 post-randomization
|
0.00%
0/198 • Up to Day 43 post-randomization
|
Other adverse events
| Measure |
Nabiximols
n=199 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 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
|
Placebo (GA-0034)
n=198 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
4.0%
8/199 • Up to Day 43 post-randomization
|
6.6%
13/198 • Up to Day 43 post-randomization
|
|
Gastrointestinal disorders
Nausea
|
9.5%
19/199 • Up to Day 43 post-randomization
|
8.1%
16/198 • Up to Day 43 post-randomization
|
|
Gastrointestinal disorders
Vomiting
|
8.5%
17/199 • Up to Day 43 post-randomization
|
6.6%
13/198 • Up to Day 43 post-randomization
|
|
Nervous system disorders
Dizziness
|
8.0%
16/199 • Up to Day 43 post-randomization
|
4.5%
9/198 • Up to Day 43 post-randomization
|
|
Nervous system disorders
Somnolence
|
11.6%
23/199 • Up to Day 43 post-randomization
|
4.0%
8/198 • Up to Day 43 post-randomization
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60