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Trial record 13 of 56 for:    insys

Study of Buprenorphine Sublingual Spray for the Treatment of Moderate to Severe Pain

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ClinicalTrials.gov Identifier: NCT02634788
Recruitment Status : Completed
First Posted : December 18, 2015
Results First Posted : August 14, 2017
Last Update Posted : August 14, 2017
Sponsor:
Information provided by (Responsible Party):
INSYS Therapeutics Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pain
Interventions Drug: Buprenorphine
Drug: Placebo
Enrollment 322
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days. Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days. Participants received buprenorphine 0.25 mg sublingual spray TID for two days. Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Period Title: Overall Study
Started 79 81 80 82
Completed 75 71 75 77
Not Completed 4 10 5 5
Reason Not Completed
Adverse Event             0             8             3             1
Lack of Efficacy             4             0             1             4
Lost to Follow-up             0             1             0             0
Withdrawal by Subject             0             1             1             0
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID Total
Hide Arm/Group Description Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days. Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days. Participants received buprenorphine 0.25 mg sublingual spray TID for two days. Participants received buprenorphine 0.125 mg sublingual spray TID for two days. Total of all reporting groups
Overall Number of Baseline Participants 79 81 80 82 322
Hide Baseline Analysis Population Description
Safety Population included all participants who were treated with the study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 79 participants 81 participants 80 participants 82 participants 322 participants
45.3  (14.55) 43.7  (14.17) 45.6  (11.78) 48.4  (11.75) 45.7  (13.17)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 81 participants 80 participants 82 participants 322 participants
Female
63
  79.7%
64
  79.0%
64
  80.0%
63
  76.8%
254
  78.9%
Male
16
  20.3%
17
  21.0%
16
  20.0%
19
  23.2%
68
  21.1%
1.Primary Outcome
Title Numeric Rating Scale (NRS) Summed Pain Intensity Difference (SPID) Over 0 to 48 Hours After Time 0 (NRS SPID-48)
Hide Description 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.
Time Frame Baseline and 0 to 48 hours after Time 0
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 75 72 75 77
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
89.40  (10.109) 171.33  (10.316) 125.58  (10.101) 124.85  (9.944)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Buprenorphine 0.5 mg TID
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments The analysis included treatment and site as main effects and Baseline pain intensity as the covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 81.93
Confidence Interval (2-Sided) 95%
53.82 to 110.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 14.283
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Buprenorphine 0.25 mg TID
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0108
Comments [Not Specified]
Method ANCOVA
Comments The analysis included treatment and site as main effects and Baseline pain intensity as the covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 36.18
Confidence Interval (2-Sided) 95%
8.43 to 63.93
Parameter Dispersion
Type: Standard Error of the Mean
Value: 14.099
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Buprenorphine 0.125 mg TID
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0120
Comments [Not Specified]
Method ANCOVA
Comments The analysis included treatment and site as main effects and Baseline pain intensity as the covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 35.46
Confidence Interval (2-Sided) 95%
7.86 to 63.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 14.020
Estimation Comments [Not Specified]
2.Secondary Outcome
Title NRS Mean Pain Intensity Difference (PID) at 4, 8, 24 and 48 Hours After Time 0
Hide Description 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.
Time Frame Baseline and 4, 8, 24 and 48 hours after Time 0
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population with data available at each timepoint.
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 79 81 80 82
Mean (Standard Deviation)
Unit of Measure: units on a scale
4 Hours Number Analyzed 78 participants 81 participants 80 participants 80 participants
-0.1  (2.13) 2.6  (3.26) 0.9  (3.14) 1.1  (3.21)
8 Hours Number Analyzed 77 participants 78 participants 78 participants 78 participants
0.5  (2.10) 2.5  (3.06) 1.2  (2.78) 0.7  (2.73)
24 Hours Number Analyzed 75 participants 73 participants 76 participants 77 participants
2.2  (2.59) 4.0  (2.64) 3.0  (2.72) 3.2  (2.98)
48 Hours Number Analyzed 75 participants 72 participants 75 participants 77 participants
3.5  (2.60) 4.9  (2.33) 3.5  (3.00) 4.1  (2.89)
3.Secondary Outcome
Title NRS Mean Pain Intensity Score at 4, 8, 24 and 48 Hours After Time 0
Hide Description 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.
Time Frame 4, 8, 24 and 48 hours after Time 0
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population with data available at each timepoint.
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 79 81 80 82
Mean (Standard Deviation)
Unit of Measure: units on a scale
4 Hours Number Analyzed 78 participants 81 participants 80 participants 80 participants
6.5  (2.45) 4.1  (3.46) 5.5  (3.24) 5.6  (3.24)
8 Hours Number Analyzed 77 participants 78 participants 78 participants 78 participants
5.9  (2.51) 4.2  (2.76) 5.1  (2.75) 5.9  (2.57)
24 Hours Number Analyzed 75 participants 73 participants 76 participants 77 participants
4.2  (2.67) 2.7  (2.39) 3.4  (2.55) 3.4  (2.68)
48 Hours Number Analyzed 75 participants 72 participants 75 participants 77 participants
2.9  (2.60) 1.9  (1.95) 2.8  (2.65) 2.6  (2.56)
4.Secondary Outcome
Title NRS SPID Over 4 Hours (SPID-4), 8 Hours (SPID-8) and 24 Hours (SPID-24) After Time 0
Hide Description 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.
Time Frame Baseline and 0 to 4, 0 to 8 and 0 to 24 hours after Time 0
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the Intent-to-Treat (ITT) Population who did not have missing SPID values.
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 78 81 80 82
Least Squares Mean (Standard Deviation)
Unit of Measure: units on a scale
SPID-4 Number Analyzed 78 participants 81 participants 80 participants 80 participants
0.67  (1.036) 7.70  (1.013) 3.67  (1.023) 3.74  (1.020)
SPID-8 Number Analyzed 77 participants 78 participants 78 participants 78 participants
1.32  (1.851) 17.57  (1.835) 8.26  (1.843) 7.08  (1.837)
SPID-24 Number Analyzed 75 participants 73 participants 76 participants 77 participants
24.16  (5.001) 75.67  (5.066) 48.85  (4.962) 44.17  (4.920)
5.Secondary Outcome
Title Total Pain Relief (TOTPAR) Over 4, 8, 24 and 48 Hours After Time 0
Hide Description 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.
Time Frame 4, 8, 24 and 48 hours after Time 0
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population with data available at each timepoint.
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 79 81 80 82
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
TOTPAR-4 Number Analyzed 78 participants 81 participants 80 participants 80 participants
2.50  (0.467) 6.23  (0.457) 4.07  (0.461) 4.38  (0.460)
TOTPAR-8 Number Analyzed 77 participants 78 participants 78 participants 78 participants
5.48  (0.848) 13.85  (0.841) 9.22  (0.845) 8.95  (0.842)
TOTPAR-24 Number Analyzed 75 participants 73 participants 76 participants 77 participants
27.33  (2.304) 53.30  (2.334) 40.50  (2.286) 40.45  (2.267)
TOTPAR-48 Number Analyzed 75 participants 72 participants 75 participants 77 participants
73.88  (4.684) 118.12  (4.780) 95.73  (4.680) 100.15  (4.607)
6.Secondary Outcome
Title Time to Onset of Analgesia
Hide Description 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.
Time Frame From Time 0 (first dose of study drug) to time of confirmed meaningful pain relief (up to 64 minutes)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population.
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 79 81 80 82
Median (95% Confidence Interval)
Unit of Measure: minutes
NA [1] 
(NA to NA)
43.0
(21.0 to 64.0)
NA [1] 
(43.0 to NA)
NA [1] 
(41.0 to NA)
[1]
Not estimable because less than 50% of participants achieved onset
7.Secondary Outcome
Title Percentage of Participants With Scores in Each Pain Relief Category at 4, 8, 24 and 48 Hours After Time 0
Hide Description 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.
Time Frame 4, 8, 24 and 48 hours after Time 0 (first dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 79 81 80 82
Measure Type: Number
Unit of Measure: percentage of participants
4 Hours - No relief 60.8 24.7 43.8 41.5
4 Hours - A little relief 21.5 16.0 22.5 23.2
4 Hours - Some relief 13.9 21.0 13.8 11.0
4 Hours - A lot of relief 1.3 19.8 13.8 13.4
4 Hours - Complete relief 1.3 18.5 6.3 8.5
8 Hours - No relief 43.0 18.5 32.5 32.9
8 Hours - A little relief 35.4 14.8 22.5 28.0
8 Hours - Some relief 7.6 27.2 21.3 18.3
8 Hours - A lot of relief 10.1 23.5 12.5 12.2
8 Hours - Complete relief 1.3 12.3 8.8 3.7
24 Hours - No relief 20.3 6.2 7.5 11.0
24 Hours - A little relief 19.0 2.5 21.3 12.2
24 Hours - Some relief 29.1 23.5 25.0 19.5
24 Hours - A lot of relief 17.7 38.3 26.3 39.0
24 Hours - Complete relief 8.9 19.8 15.0 12.2
48 Hours - No relief 17.7 2.5 8.8 4.9
48 Hours - A little relief 13.9 8.6 11.3 6.1
48 Hours - Some relief 20.3 12.3 20.0 20.7
48 Hours - A lot of relief 27.8 38.3 32.5 35.4
48 Hours - Complete relief 15.2 27.2 21.3 26.8
8.Secondary Outcome
Title Percentage of Participants With Peak Scores in Each Pain Relief Category
Hide Description 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.
Time Frame From Time 0 (first dose of study drug) up to 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 79 81 80 82
Measure Type: Number
Unit of Measure: percentage of participants
No relief 6.3 0 1.3 3.7
A little relief 11.4 2.5 3.8 1.2
Some relief 19.0 9.9 12.5 13.4
A lot of relief 36.7 42.0 46.3 40.2
Complete relief 26.6 45.7 36.3 41.5
A lot of relief + Complete relief 63.3 87.7 82.6 81.7
9.Secondary Outcome
Title Time to Peak Pain Relief
Hide Description 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.
Time Frame From Time 0 (first dose of study drug) to time of peak pain relief (up to 1437 minutes)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 79 81 80 82
Median (95% Confidence Interval)
Unit of Measure: minutes
1200.0
(720.0 to 1200.0)
360.0
(181.0 to 719.0)
720.0
(420.0 to 960.0)
1200.0
(720.0 to 1437.0)
10.Secondary Outcome
Title Time to First Perceptible Pain Relief
Hide Description 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.
Time Frame From Time 0 (first dose of study drug) to time of first perceptible pain relief (up to 83 minutes)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population.
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 79 81 80 82
Median (95% Confidence Interval)
Unit of Measure: minutes
29.0
(6.0 to 83.0)
23.0
(10.0 to 43.0)
15.0
(11.0 to 42.0)
27.0
(14.0 to 74.0)
11.Secondary Outcome
Title Time to Meaningful Pain Relief
Hide Description 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.
Time Frame From Time 0 (first dose of study drug) to time of meaningful pain relief (up to 227 minutes)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population.
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 79 81 80 82
Median (95% Confidence Interval)
Unit of Measure: minutes
238.0 [1] 
(121.0 to NA)
92.0
(79.0 to 120.0)
122.0
(90.0 to 227.0)
166.0
(87.0 to 240.0)
[1]
Not estimable because less than 50% of participants achieved meaningful pain relief
12.Secondary Outcome
Title Percentage of Participants Using Rescue Medication for Pain
Hide Description The percentage of participants who needed to take an alternate medication for pain relief during the treatment period.
Time Frame From Time 0 (first dose of study drug) up to 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population.
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 79 81 80 82
Measure Type: Number
Unit of Measure: percentage of participants
97.5 55.6 87.5 87.8
13.Secondary Outcome
Title Time to First Use of Rescue Medication for Pain
Hide Description 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.
Time Frame From Time 0 to time of first use of rescue medication (up to 280 minutes)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population.
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 79 81 80 82
Median (95% Confidence Interval)
Unit of Measure: minutes
107.0
(77.0 to 125.0)
937.0 [1] 
(349.0 to NA)
219.5
(105.0 to 260.0)
193.0
(92.0 to 280.0)
[1]
Not estimable because too few participants used rescue medication
14.Secondary Outcome
Title Total Use of Rescue Medication Over 0 to 24 Hours and 0 to 48 Hours
Hide Description Total use of rescue medication is defined as the number of times a participant took rescue medication.
Time Frame Over 24 and 48 hours after Time 0 (first dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population who used rescue medication during the specified time intervals.
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 77 45 70 72
Mean (Standard Deviation)
Unit of Measure: number of uses
0-24 Hours Number Analyzed 77 participants 41 participants 68 participants 71 participants
3.8  (1.98) 2.2  (1.69) 2.6  (1.62) 2.9  (1.67)
0-48 Hours Number Analyzed 77 participants 45 participants 70 participants 72 participants
5.6  (3.60) 2.9  (2.81) 3.7  (2.68) 3.9  (2.69)
15.Secondary Outcome
Title Participant's Global Evaluation of Study Drug
Hide Description 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.
Time Frame End of treatment (Day 3) or early termination
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from the ITT Population.
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description:
Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days.
Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days.
Participants received buprenorphine 0.25 mg sublingual spray TID for two days.
Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
Overall Number of Participants Analyzed 79 81 80 82
Measure Type: Number
Unit of Measure: percentage of participants
Poor 25.3 2.5 5.0 14.6
Fair 25.3 7.4 16.3 15.9
Good 19.0 16.0 26.3 14.6
Very Good 19.0 32.1 30.0 24.4
Excellent 10.1 38.3 18.8 28.0
Time Frame From the first dose of study drug to the Follow-up visit (up to 9 days).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Hide Arm/Group Description Participants received placebo-matching buprenorphine sublingual (under the tongue) spray TID for two days. Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) for two days. Participants received buprenorphine 0.25 mg sublingual spray TID for two days. Participants received buprenorphine 0.125 mg sublingual spray TID for two days.
All-Cause Mortality
Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/79 (0.00%)   1/81 (1.23%)   0/80 (0.00%)   0/82 (0.00%) 
Skin and subcutaneous tissue disorders         
Angioedema  1  0/79 (0.00%)  1/81 (1.23%)  0/80 (0.00%)  0/82 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Buprenorphine 0.5 mg TID Buprenorphine 0.25 mg TID Buprenorphine 0.125 mg TID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   38/79 (48.10%)   76/81 (93.83%)   67/80 (83.75%)   57/82 (69.51%) 
Gastrointestinal disorders         
Nausea  1  13/79 (16.46%)  68/81 (83.95%)  47/80 (58.75%)  36/82 (43.90%) 
Vomiting  1  4/79 (5.06%)  59/81 (72.84%)  33/80 (41.25%)  24/82 (29.27%) 
Constipation  1  1/79 (1.27%)  8/81 (9.88%)  6/80 (7.50%)  9/82 (10.98%) 
Investigations         
Oxygen saturation decreased  1  4/79 (5.06%)  7/81 (8.64%)  8/80 (10.00%)  6/82 (7.32%) 
Metabolism and nutrition disorders         
Dehydration  1  0/79 (0.00%)  7/81 (8.64%)  0/80 (0.00%)  0/82 (0.00%) 
Nervous system disorders         
Dizziness  1  7/79 (8.86%)  44/81 (54.32%)  26/80 (32.50%)  18/82 (21.95%) 
Headache  1  9/79 (11.39%)  13/81 (16.05%)  23/80 (28.75%)  15/82 (18.29%) 
Somnolence  1  0/79 (0.00%)  11/81 (13.58%)  6/80 (7.50%)  6/82 (7.32%) 
Skin and subcutaneous tissue disorders         
Pruritus  1  1/79 (1.27%)  11/81 (13.58%)  2/80 (2.50%)  2/82 (2.44%) 
Hyperhidrosis  1  0/79 (0.00%)  8/81 (9.88%)  1/80 (1.25%)  2/82 (2.44%) 
Vascular disorders         
Hot flush  1  1/79 (1.27%)  5/81 (6.17%)  2/80 (2.50%)  2/82 (2.44%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Director, Clinical Development
Organization: Insys Therapeutics, Inc.
Phone: 480-500-3105
Responsible Party: INSYS Therapeutics Inc
ClinicalTrials.gov Identifier: NCT02634788     History of Changes
Other Study ID Numbers: INS005-15-062
First Submitted: December 16, 2015
First Posted: December 18, 2015
Results First Submitted: June 1, 2017
Results First Posted: August 14, 2017
Last Update Posted: August 14, 2017