Trial Outcomes & Findings for Study of Buprenorphine Sublingual Spray for the Treatment of Moderate to Severe Pain (NCT NCT02634788)
NCT ID: NCT02634788
Last Updated: 2017-08-14
Results Overview
Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 48 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain \[maximum(max)=10 at each time point\], and negative numbers indicate an increase in pain \[minimum(min)=-10 at each time point\]. The overall min and max are -10 and 10 times the number of hours specified; SPID-48 range is -480 to 480. The NRS SPID-48 was analyzed using an analysis of covariance (ANCOVA) model, which included treatment and site as main effects and Baseline pain intensity as the covariate.
COMPLETED
PHASE3
322 participants
Baseline and 0 to 48 hours after Time 0
2017-08-14
Participant Flow
Participant milestones
| Measure |
Placebo
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
79
|
81
|
80
|
82
|
|
Overall Study
COMPLETED
|
75
|
71
|
75
|
77
|
|
Overall Study
NOT COMPLETED
|
4
|
10
|
5
|
5
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
8
|
3
|
1
|
|
Overall Study
Lack of Efficacy
|
4
|
0
|
1
|
4
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
1
|
0
|
Baseline Characteristics
Study of Buprenorphine Sublingual Spray for the Treatment of Moderate to Severe Pain
Baseline characteristics by cohort
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
Total
n=322 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
45.3 years
STANDARD_DEVIATION 14.55 • n=5 Participants
|
43.7 years
STANDARD_DEVIATION 14.17 • n=7 Participants
|
45.6 years
STANDARD_DEVIATION 11.78 • n=5 Participants
|
48.4 years
STANDARD_DEVIATION 11.75 • n=4 Participants
|
45.7 years
STANDARD_DEVIATION 13.17 • n=21 Participants
|
|
Sex: Female, Male
Female
|
63 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
64 Participants
n=5 Participants
|
63 Participants
n=4 Participants
|
254 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
68 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline and 0 to 48 hours after Time 0Population: All randomized participants from the Intent-to-Treat (ITT) Population who did not have missing SPID-48 values. Missing SPID-48 data were not imputed.
Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 48 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain \[maximum(max)=10 at each time point\], and negative numbers indicate an increase in pain \[minimum(min)=-10 at each time point\]. The overall min and max are -10 and 10 times the number of hours specified; SPID-48 range is -480 to 480. The NRS SPID-48 was analyzed using an analysis of covariance (ANCOVA) model, which included treatment and site as main effects and Baseline pain intensity as the covariate.
Outcome measures
| Measure |
Placebo
n=75 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=72 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=75 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=77 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Numeric Rating Scale (NRS) Summed Pain Intensity Difference (SPID) Over 0 to 48 Hours After Time 0 (NRS SPID-48)
|
89.40 units on a scale
Standard Error 10.109
|
171.33 units on a scale
Standard Error 10.316
|
125.58 units on a scale
Standard Error 10.101
|
124.85 units on a scale
Standard Error 9.944
|
SECONDARY outcome
Timeframe: Baseline and 4, 8, 24 and 48 hours after Time 0Population: All randomized participants from the ITT Population with data available at each timepoint.
Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug administration) and at multiple time points up to 48 hours after Time 0 (time of administration of the first dose of study drug). NRS PID is defined as the difference in pain at each scheduled timepoint relative to Baseline (PID=pain intensity at baseline - pain intensity at time point). A higher value of NRS PID score indicates a higher decrease in pain from Baseline.
Outcome measures
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
NRS Mean Pain Intensity Difference (PID) at 4, 8, 24 and 48 Hours After Time 0
48 Hours
|
3.5 units on a scale
Standard Deviation 2.60
|
4.9 units on a scale
Standard Deviation 2.33
|
3.5 units on a scale
Standard Deviation 3.00
|
4.1 units on a scale
Standard Deviation 2.89
|
|
NRS Mean Pain Intensity Difference (PID) at 4, 8, 24 and 48 Hours After Time 0
4 Hours
|
-0.1 units on a scale
Standard Deviation 2.13
|
2.6 units on a scale
Standard Deviation 3.26
|
0.9 units on a scale
Standard Deviation 3.14
|
1.1 units on a scale
Standard Deviation 3.21
|
|
NRS Mean Pain Intensity Difference (PID) at 4, 8, 24 and 48 Hours After Time 0
8 Hours
|
0.5 units on a scale
Standard Deviation 2.10
|
2.5 units on a scale
Standard Deviation 3.06
|
1.2 units on a scale
Standard Deviation 2.78
|
0.7 units on a scale
Standard Deviation 2.73
|
|
NRS Mean Pain Intensity Difference (PID) at 4, 8, 24 and 48 Hours After Time 0
24 Hours
|
2.2 units on a scale
Standard Deviation 2.59
|
4.0 units on a scale
Standard Deviation 2.64
|
3.0 units on a scale
Standard Deviation 2.72
|
3.2 units on a scale
Standard Deviation 2.98
|
SECONDARY outcome
Timeframe: 4, 8, 24 and 48 hours after Time 0Population: All randomized participants from the ITT Population with data available at each timepoint.
Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug administration) and at multiple time points up to 48 hours after Time 0 (time of administration of the first dose of study drug). A lower value indicates improvement in pain.
Outcome measures
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
NRS Mean Pain Intensity Score at 4, 8, 24 and 48 Hours After Time 0
48 Hours
|
2.9 units on a scale
Standard Deviation 2.60
|
1.9 units on a scale
Standard Deviation 1.95
|
2.8 units on a scale
Standard Deviation 2.65
|
2.6 units on a scale
Standard Deviation 2.56
|
|
NRS Mean Pain Intensity Score at 4, 8, 24 and 48 Hours After Time 0
4 Hours
|
6.5 units on a scale
Standard Deviation 2.45
|
4.1 units on a scale
Standard Deviation 3.46
|
5.5 units on a scale
Standard Deviation 3.24
|
5.6 units on a scale
Standard Deviation 3.24
|
|
NRS Mean Pain Intensity Score at 4, 8, 24 and 48 Hours After Time 0
8 Hours
|
5.9 units on a scale
Standard Deviation 2.51
|
4.2 units on a scale
Standard Deviation 2.76
|
5.1 units on a scale
Standard Deviation 2.75
|
5.9 units on a scale
Standard Deviation 2.57
|
|
NRS Mean Pain Intensity Score at 4, 8, 24 and 48 Hours After Time 0
24 Hours
|
4.2 units on a scale
Standard Deviation 2.67
|
2.7 units on a scale
Standard Deviation 2.39
|
3.4 units on a scale
Standard Deviation 2.55
|
3.4 units on a scale
Standard Deviation 2.68
|
SECONDARY outcome
Timeframe: Baseline and 0 to 4, 0 to 8 and 0 to 24 hours after Time 0Population: All randomized participants from the Intent-to-Treat (ITT) Population who did not have missing SPID values.
Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 48 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain \[max=10 at each time point\] and negative numbers indicate an increase in pain \[min=-10 at each time point\]. The overall min and max are -10 and 10 times the number of hours specified: SPID-4=(-40 to 40), SPID-8=(-80 to 80) and SPID-24=(-240 to 240). The NRS SPID-4, 8 and 24 were analyzed using an ANCOVA model which included treatment and site as main effects and Baseline pain intensity as the covariate.
Outcome measures
| Measure |
Placebo
n=78 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
NRS SPID Over 4 Hours (SPID-4), 8 Hours (SPID-8) and 24 Hours (SPID-24) After Time 0
SPID-8
|
1.32 units on a scale
Standard Deviation 1.851
|
17.57 units on a scale
Standard Deviation 1.835
|
8.26 units on a scale
Standard Deviation 1.843
|
7.08 units on a scale
Standard Deviation 1.837
|
|
NRS SPID Over 4 Hours (SPID-4), 8 Hours (SPID-8) and 24 Hours (SPID-24) After Time 0
SPID-4
|
0.67 units on a scale
Standard Deviation 1.036
|
7.70 units on a scale
Standard Deviation 1.013
|
3.67 units on a scale
Standard Deviation 1.023
|
3.74 units on a scale
Standard Deviation 1.020
|
|
NRS SPID Over 4 Hours (SPID-4), 8 Hours (SPID-8) and 24 Hours (SPID-24) After Time 0
SPID-24
|
24.16 units on a scale
Standard Deviation 5.001
|
75.67 units on a scale
Standard Deviation 5.066
|
48.85 units on a scale
Standard Deviation 4.962
|
44.17 units on a scale
Standard Deviation 4.920
|
SECONDARY outcome
Timeframe: 4, 8, 24 and 48 hours after Time 0Population: All randomized participants from the ITT Population with data available at each timepoint.
TOTPAR was assessed by the participant using a 5-point NRS (0=no relief, 1=a little, 2=some, 3=a lot, 4=complete relief). TOTPAR scores were collected at Baseline (prior to study drug) and at multiple time points up to 48 hours after Time 0 (first dose of study drug). The TOTPAR scores are the sum of the pain relief at each time point multiplied by the duration in hours since the previous time point. Larger positive numbers indicate more pain relief (maximum=4 at each time point) and smaller positive numbers indicate less pain relief (minimum=0 at each time point). The overall minimum is 0 for each variable and the overall maximum is 4 times the number of hours specified for the variable: TOTPAR-4=(0 to 16), TOTPAR-8=(0 to 32), TOTPAR-24=(0 to 96) and TOTPAR-48=(0 to 192). TOTPAR-4, TOTPAR-8, TOTPAR-24 and TOTPAR-48 were analyzed using an ANCOVA model with factors for treatment, site and baseline pain intensity.
Outcome measures
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Total Pain Relief (TOTPAR) Over 4, 8, 24 and 48 Hours After Time 0
TOTPAR-4
|
2.50 units on a scale
Standard Error 0.467
|
6.23 units on a scale
Standard Error 0.457
|
4.07 units on a scale
Standard Error 0.461
|
4.38 units on a scale
Standard Error 0.460
|
|
Total Pain Relief (TOTPAR) Over 4, 8, 24 and 48 Hours After Time 0
TOTPAR-8
|
5.48 units on a scale
Standard Error 0.848
|
13.85 units on a scale
Standard Error 0.841
|
9.22 units on a scale
Standard Error 0.845
|
8.95 units on a scale
Standard Error 0.842
|
|
Total Pain Relief (TOTPAR) Over 4, 8, 24 and 48 Hours After Time 0
TOTPAR-24
|
27.33 units on a scale
Standard Error 2.304
|
53.30 units on a scale
Standard Error 2.334
|
40.50 units on a scale
Standard Error 2.286
|
40.45 units on a scale
Standard Error 2.267
|
|
Total Pain Relief (TOTPAR) Over 4, 8, 24 and 48 Hours After Time 0
TOTPAR-48
|
73.88 units on a scale
Standard Error 4.684
|
118.12 units on a scale
Standard Error 4.780
|
95.73 units on a scale
Standard Error 4.680
|
100.15 units on a scale
Standard Error 4.607
|
SECONDARY outcome
Timeframe: From Time 0 (first dose of study drug) to time of confirmed meaningful pain relief (up to 64 minutes)Population: All randomized participants from the ITT Population.
Time to onset of analgesia was measured as time to first perceptible pain relief confirmed by meaningful pain relief using the 2-stopwatch method. The study staff started 2 stopwatches as soon as the first dose of study drug was administered. Each participant was instructed to stop the first stopwatch when he or she experienced any perceptible pain relief and the second stopwatch when he or she experienced pain relief that was meaningful to them. If the second stopwatch was not stopped, time was censored at the time of the second dose of study drug or the use of rescue medication, whichever came first. If both stopwatches were not stopped time was censored at the time of the second dose of study drug or the use of rescue medication whichever came first. Time to onset of analgesia was defined as the time when the first stopwatch was stopped given that the second stopwatch is stopped.
Outcome measures
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Time to Onset of Analgesia
|
NA minutes
Not estimable because less than 50% of participants achieved onset
|
43.0 minutes
Interval 21.0 to 64.0
|
NA minutes
Interval 43.0 to
Not estimable because less than 50% of participants achieved onset
|
NA minutes
Interval 41.0 to
Not estimable because less than 50% of participants achieved onset
|
SECONDARY outcome
Timeframe: 4, 8, 24 and 48 hours after Time 0 (first dose of study drug)Population: All randomized participants from the ITT Population
Pain relief was assessed by the participant using a 5-point NRS (0=no relief, 1=a little, 2=some, 3=a lot, 4=complete relief). The percentage of participants with scores in each pain relief category are reported. Missing values were imputed.
Outcome measures
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
4 Hours - No relief
|
60.8 percentage of participants
|
24.7 percentage of participants
|
43.8 percentage of participants
|
41.5 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
4 Hours - Complete relief
|
1.3 percentage of participants
|
18.5 percentage of participants
|
6.3 percentage of participants
|
8.5 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
4 Hours - A lot of relief
|
1.3 percentage of participants
|
19.8 percentage of participants
|
13.8 percentage of participants
|
13.4 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
8 Hours - No relief
|
43.0 percentage of participants
|
18.5 percentage of participants
|
32.5 percentage of participants
|
32.9 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
8 Hours - A little relief
|
35.4 percentage of participants
|
14.8 percentage of participants
|
22.5 percentage of participants
|
28.0 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
8 Hours - Some relief
|
7.6 percentage of participants
|
27.2 percentage of participants
|
21.3 percentage of participants
|
18.3 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
8 Hours - A lot of relief
|
10.1 percentage of participants
|
23.5 percentage of participants
|
12.5 percentage of participants
|
12.2 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
8 Hours - Complete relief
|
1.3 percentage of participants
|
12.3 percentage of participants
|
8.8 percentage of participants
|
3.7 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
24 Hours - No relief
|
20.3 percentage of participants
|
6.2 percentage of participants
|
7.5 percentage of participants
|
11.0 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
24 Hours - A little relief
|
19.0 percentage of participants
|
2.5 percentage of participants
|
21.3 percentage of participants
|
12.2 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
24 Hours - Some relief
|
29.1 percentage of participants
|
23.5 percentage of participants
|
25.0 percentage of participants
|
19.5 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
24 Hours - A lot of relief
|
17.7 percentage of participants
|
38.3 percentage of participants
|
26.3 percentage of participants
|
39.0 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
24 Hours - Complete relief
|
8.9 percentage of participants
|
19.8 percentage of participants
|
15.0 percentage of participants
|
12.2 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
48 Hours - No relief
|
17.7 percentage of participants
|
2.5 percentage of participants
|
8.8 percentage of participants
|
4.9 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
48 Hours - A little relief
|
13.9 percentage of participants
|
8.6 percentage of participants
|
11.3 percentage of participants
|
6.1 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
48 Hours - Some relief
|
20.3 percentage of participants
|
12.3 percentage of participants
|
20.0 percentage of participants
|
20.7 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
48 Hours - A lot of relief
|
27.8 percentage of participants
|
38.3 percentage of participants
|
32.5 percentage of participants
|
35.4 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
48 Hours - Complete relief
|
15.2 percentage of participants
|
27.2 percentage of participants
|
21.3 percentage of participants
|
26.8 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
4 Hours - A little relief
|
21.5 percentage of participants
|
16.0 percentage of participants
|
22.5 percentage of participants
|
23.2 percentage of participants
|
|
Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
4 Hours - Some relief
|
13.9 percentage of participants
|
21.0 percentage of participants
|
13.8 percentage of participants
|
11.0 percentage of participants
|
SECONDARY outcome
Timeframe: From Time 0 (first dose of study drug) up to 48 hoursPopulation: All randomized participants from the ITT Population
Peak pain relief is the highest value of pain relief experienced during the study. Pain relief was assessed by the participant using a 5-point NRS (0=no relief, 1=a little, 2=some, 3=a lot, 4=complete relief). The percentage of participants with peak scores in each pain relief category are reported.
Outcome measures
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Percentage of Participants With Peak Scores in Each Pain Relief Category
No relief
|
6.3 percentage of participants
|
0 percentage of participants
|
1.3 percentage of participants
|
3.7 percentage of participants
|
|
Percentage of Participants With Peak Scores in Each Pain Relief Category
A little relief
|
11.4 percentage of participants
|
2.5 percentage of participants
|
3.8 percentage of participants
|
1.2 percentage of participants
|
|
Percentage of Participants With Peak Scores in Each Pain Relief Category
Some relief
|
19.0 percentage of participants
|
9.9 percentage of participants
|
12.5 percentage of participants
|
13.4 percentage of participants
|
|
Percentage of Participants With Peak Scores in Each Pain Relief Category
A lot of relief
|
36.7 percentage of participants
|
42.0 percentage of participants
|
46.3 percentage of participants
|
40.2 percentage of participants
|
|
Percentage of Participants With Peak Scores in Each Pain Relief Category
Complete relief
|
26.6 percentage of participants
|
45.7 percentage of participants
|
36.3 percentage of participants
|
41.5 percentage of participants
|
|
Percentage of Participants With Peak Scores in Each Pain Relief Category
A lot of relief + Complete relief
|
63.3 percentage of participants
|
87.7 percentage of participants
|
82.6 percentage of participants
|
81.7 percentage of participants
|
SECONDARY outcome
Timeframe: From Time 0 (first dose of study drug) to time of peak pain relief (up to 1437 minutes)Population: All randomized participants from the ITT Population
Time to peak pain relief is the time to the highest value of pain relief experienced during the study. Pain relief was assessed by the participant using a 5-point NRS (0=no relief, 1=a little, 2=some, 3=a lot, 4=complete relief). If no pain relief was observed, then the time was censored at the time of the last pain assessment.
Outcome measures
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Time to Peak Pain Relief
|
1200.0 minutes
Interval 720.0 to 1200.0
|
360.0 minutes
Interval 181.0 to 719.0
|
720.0 minutes
Interval 420.0 to 960.0
|
1200.0 minutes
Interval 720.0 to 1437.0
|
SECONDARY outcome
Timeframe: From Time 0 (first dose of study drug) to time of first perceptible pain relief (up to 83 minutes)Population: All randomized participants from the ITT Population.
Time to first perceptible pain relief was evaluated using the 2 stopwatch method and is defined as the time when the participant stops the first stopwatch. If it was not stopped time was censored at the time that the second stopwatch was stopped or the time of the second dose or the time that rescue medication was used whichever came first.
Outcome measures
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Time to First Perceptible Pain Relief
|
29.0 minutes
Interval 6.0 to 83.0
|
23.0 minutes
Interval 10.0 to 43.0
|
15.0 minutes
Interval 11.0 to 42.0
|
27.0 minutes
Interval 14.0 to 74.0
|
SECONDARY outcome
Timeframe: From Time 0 (first dose of study drug) to time of meaningful pain relief (up to 227 minutes)Population: All randomized participants from the ITT Population.
Time to meaningful pain relief was evaluated using the 2 stopwatch method and is defined as the time when the participant stops the second stopwatch. If it was not stopped time was censored at the time that the second stopwatch was stopped or the time of the second dose or the time that rescue medication was used whichever came first.
Outcome measures
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Time to Meaningful Pain Relief
|
238.0 minutes
Interval 121.0 to
Not estimable because less than 50% of participants achieved meaningful pain relief
|
92.0 minutes
Interval 79.0 to 120.0
|
122.0 minutes
Interval 90.0 to 227.0
|
166.0 minutes
Interval 87.0 to 240.0
|
SECONDARY outcome
Timeframe: From Time 0 (first dose of study drug) up to 48 hoursPopulation: All randomized participants from the ITT Population.
The percentage of participants who needed to take an alternate medication for pain relief during the treatment period.
Outcome measures
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Percentage of Participants Using Rescue Medication for Pain
|
97.5 percentage of participants
|
55.6 percentage of participants
|
87.5 percentage of participants
|
87.8 percentage of participants
|
SECONDARY outcome
Timeframe: From Time 0 to time of first use of rescue medication (up to 280 minutes)Population: All randomized participants from the ITT Population.
Time to first use of rescue medication is the time from Time 0 (time of administration of the first dose of study drug) to the first use of rescue medication. If rescue medication was not taken the time was censored at the time of the last pain assessment.
Outcome measures
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Time to First Use of Rescue Medication for Pain
|
107.0 minutes
Interval 77.0 to 125.0
|
937.0 minutes
Interval 349.0 to
Not estimable because too few participants used rescue medication
|
219.5 minutes
Interval 105.0 to 260.0
|
193.0 minutes
Interval 92.0 to 280.0
|
SECONDARY outcome
Timeframe: Over 24 and 48 hours after Time 0 (first dose of study drug)Population: All randomized participants from the ITT Population who used rescue medication during the specified time intervals.
Total use of rescue medication is defined as the number of times a participant took rescue medication.
Outcome measures
| Measure |
Placebo
n=77 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=45 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=70 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=72 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Total Use of Rescue Medication Over 0 to 24 Hours and 0 to 48 Hours
0-24 Hours
|
3.8 number of uses
Standard Deviation 1.98
|
2.2 number of uses
Standard Deviation 1.69
|
2.6 number of uses
Standard Deviation 1.62
|
2.9 number of uses
Standard Deviation 1.67
|
|
Total Use of Rescue Medication Over 0 to 24 Hours and 0 to 48 Hours
0-48 Hours
|
5.6 number of uses
Standard Deviation 3.60
|
2.9 number of uses
Standard Deviation 2.81
|
3.7 number of uses
Standard Deviation 2.68
|
3.9 number of uses
Standard Deviation 2.69
|
SECONDARY outcome
Timeframe: End of treatment (Day 3) or early terminationPopulation: All randomized participants from the ITT Population.
Global evaluation of study drug was completed at the end of treatment (Day 3) or before early termination if a participant discontinued early. Participants were asked to provide an overall rating of their study medication in controlling pain on a 5-point NRS, where 0=poor, 1=fair, 2=good, 3=very good, and 4=excellent. The percentage of participants with scores in each pain relief category are reported.
Outcome measures
| Measure |
Placebo
n=79 Participants
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 Participants
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 Participants
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 Participants
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Participant's Global Evaluation of Study Drug
Poor
|
25.3 percentage of participants
|
2.5 percentage of participants
|
5.0 percentage of participants
|
14.6 percentage of participants
|
|
Participant's Global Evaluation of Study Drug
Fair
|
25.3 percentage of participants
|
7.4 percentage of participants
|
16.3 percentage of participants
|
15.9 percentage of participants
|
|
Participant's Global Evaluation of Study Drug
Good
|
19.0 percentage of participants
|
16.0 percentage of participants
|
26.3 percentage of participants
|
14.6 percentage of participants
|
|
Participant's Global Evaluation of Study Drug
Very Good
|
19.0 percentage of participants
|
32.1 percentage of participants
|
30.0 percentage of participants
|
24.4 percentage of participants
|
|
Participant's Global Evaluation of Study Drug
Excellent
|
10.1 percentage of participants
|
38.3 percentage of participants
|
18.8 percentage of participants
|
28.0 percentage of participants
|
Adverse Events
Placebo
Buprenorphine 0.5 mg TID
Buprenorphine 0.25 mg TID
Buprenorphine 0.125 mg TID
Serious adverse events
| Measure |
Placebo
n=79 participants at risk
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 participants at risk
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 participants at risk
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 participants at risk
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/79 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
1.2%
1/81 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
0.00%
0/80 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
0.00%
0/82 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
Other adverse events
| Measure |
Placebo
n=79 participants at risk
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
|
Buprenorphine 0.5 mg TID
n=81 participants at risk
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
|
Buprenorphine 0.25 mg TID
n=80 participants at risk
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
|
Buprenorphine 0.125 mg TID
n=82 participants at risk
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
16.5%
13/79 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
84.0%
68/81 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
58.8%
47/80 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
43.9%
36/82 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
|
Gastrointestinal disorders
Vomiting
|
5.1%
4/79 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
72.8%
59/81 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
41.2%
33/80 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
29.3%
24/82 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
|
Gastrointestinal disorders
Constipation
|
1.3%
1/79 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
9.9%
8/81 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
7.5%
6/80 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
11.0%
9/82 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
|
Nervous system disorders
Dizziness
|
8.9%
7/79 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
54.3%
44/81 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
32.5%
26/80 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
22.0%
18/82 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
|
Nervous system disorders
Headache
|
11.4%
9/79 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
16.0%
13/81 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
28.7%
23/80 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
18.3%
15/82 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
|
Nervous system disorders
Somnolence
|
0.00%
0/79 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
13.6%
11/81 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
7.5%
6/80 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
7.3%
6/82 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.3%
1/79 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
13.6%
11/81 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
2.5%
2/80 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
2.4%
2/82 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/79 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
9.9%
8/81 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
1.2%
1/80 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
2.4%
2/82 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
|
Investigations
Oxygen saturation decreased
|
5.1%
4/79 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
8.6%
7/81 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
10.0%
8/80 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
7.3%
6/82 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/79 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
8.6%
7/81 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
0.00%
0/80 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
0.00%
0/82 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
|
Vascular disorders
Hot flush
|
1.3%
1/79 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
6.2%
5/81 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
2.5%
2/80 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
2.4%
2/82 • From the first dose of study drug to the Follow-up visit (up to 9 days).
|
Additional Information
Director, Clinical Development
Insys Therapeutics, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place