Trial Outcomes & Findings for Buprenorphine's Dose Response Curve (NCT NCT00460239)
NCT ID: NCT00460239
Last Updated: 2017-03-03
Results Overview
Opioid agonist effects measured by peak change from baseline drug effect visual analog scale. Scores range from 0 (not all all) to 100 (extremely); higher scores indicate a stronger drug effect.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Results posted on
2017-03-03
Participant Flow
Participant milestones
| Measure |
Condition 1
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): B8, B16, B32, B48, B60, M15, M30, P.
|
Condition 2
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): B8, B16, B32, M15, B48, P, B60, M30.
|
Condition 3
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): B8, B16, B32, B48, M30, B60, P, M15.
|
Condition 4
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): B8, M15, B16, P, B32, M30, B48, B60.
|
Condition 5
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): B8, B16, M30, B32, P, B48, M15, B60.
|
Condition 6
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): M15, P, B8, M30, B16, B32, P, B48, B60.
|
Condition 7
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): M30, B8, P, B16, M15, B32, B48, B60.
|
Condition 8
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): P, M30, M15, B8, B16, B32, B48, B60.
|
Condition 9
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): M15, B8, B16, B32, M30, P, B48, B60.
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|---|---|---|---|---|---|---|---|---|---|
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Overall Study
STARTED
|
0
|
3
|
1
|
0
|
1
|
4
|
1
|
1
|
1
|
|
Overall Study
COMPLETED
|
0
|
2
|
1
|
0
|
1
|
1
|
1
|
1
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
3
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Condition 1
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): B8, B16, B32, B48, B60, M15, M30, P.
|
Condition 2
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): B8, B16, B32, M15, B48, P, B60, M30.
|
Condition 3
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): B8, B16, B32, B48, M30, B60, P, M15.
|
Condition 4
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): B8, M15, B16, P, B32, M30, B48, B60.
|
Condition 5
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): B8, B16, M30, B32, P, B48, M15, B60.
|
Condition 6
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): M15, P, B8, M30, B16, B32, P, B48, B60.
|
Condition 7
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): M30, B8, P, B16, M15, B32, B48, B60.
|
Condition 8
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): P, M30, M15, B8, B16, B32, B48, B60.
|
Condition 9
Participants receive single doses of intramuscular (IM) test drugs; there were 9 possible test drugs (placebo \[P\], 2 doses of morphine \[M\], 5 doses of buprenorphine \[B\]), with at least 3 days between IM injections. For this condition, the order of dosing was (numbers represent doses in mg): M15, B8, B16, B32, M30, P, B48, B60.
|
|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
Physician Decision
|
0
|
1
|
0
|
0
|
0
|
2
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Buprenorphine's Dose Response Curve
Baseline characteristics by cohort
| Measure |
All Study Participants
n=12 Participants
All Study Participants
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
39.2 years
STANDARD_DEVIATION 6.48 • n=5 Participants
|
|
Gender
Female
|
0 Participants
n=5 Participants
|
|
Gender
Male
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)Population: Subjects who completed all test conditions.
Opioid agonist effects measured by peak change from baseline drug effect visual analog scale. Scores range from 0 (not all all) to 100 (extremely); higher scores indicate a stronger drug effect.
Outcome measures
| Measure |
Placebo 0 mg
n=8 Participants
|
Morphine 15 mg
n=8 Participants
|
Morphine 30 mg
n=8 Participants
|
Buprenorphine 8 mg
n=8 Participants
|
Buprenorphine 16 mg
n=8 Participants
|
Buprenorphine 32 mg
n=8 Participants
|
Buprenorphine 48 mg
n=8 Participants
|
Buprenorphine 60 mg
n=8 Participants
|
|---|---|---|---|---|---|---|---|---|
|
Peak Change From Baseline in Drug Effect Assessed by Visual Analog Scale (VAS)
|
17.75 units on a scale
Standard Error 22.41
|
27.25 units on a scale
Standard Error 33.50
|
29.63 units on a scale
Standard Error 43.29
|
58.25 units on a scale
Standard Error 32.58
|
48.50 units on a scale
Standard Error 41.19
|
40.25 units on a scale
Standard Error 35.07
|
57.63 units on a scale
Standard Error 40.41
|
41.63 units on a scale
Standard Error 36.56
|
PRIMARY outcome
Timeframe: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)Digit Symbol Substitution Test (DSST) is a sub-test within the Wechsler Adult Intelligence Scale and is frequently used to assess psychomotor performance changes associated with drug effects. The higher the percent correct on this measure the better the performance.
Outcome measures
| Measure |
Placebo 0 mg
n=8 Participants
|
Morphine 15 mg
n=8 Participants
|
Morphine 30 mg
n=8 Participants
|
Buprenorphine 8 mg
n=8 Participants
|
Buprenorphine 16 mg
n=8 Participants
|
Buprenorphine 32 mg
n=8 Participants
|
Buprenorphine 48 mg
n=8 Participants
|
Buprenorphine 60 mg
n=8 Participants
|
|---|---|---|---|---|---|---|---|---|
|
Psychomotor/Cognitive Performance Effects Assessed by Digit Symbol Substitution Test (DSST)
|
94.03 percentage of correct answers
Standard Deviation 10.21
|
91.60 percentage of correct answers
Standard Deviation 16.55
|
89.44 percentage of correct answers
Standard Deviation 18.33
|
90.91 percentage of correct answers
Standard Deviation 10.35
|
86.60 percentage of correct answers
Standard Deviation 19.98
|
83.17 percentage of correct answers
Standard Deviation 24.80
|
85.86 percentage of correct answers
Standard Deviation 19.21
|
77.99 percentage of correct answers
Standard Deviation 27.57
|
PRIMARY outcome
Timeframe: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)Population: Subjects who completed all test conditions.
The Trails B task specifically measures set shifting and executive functioning within the Trail-Making Test. Part B consists of 25 circles distributed over a sheet of paper. Participants are asked to connect the circles in an ascending pattern, alternating between numbers and letters (i.e., 1-A-2-B-3-C, etc.). Results are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment.
Outcome measures
| Measure |
Placebo 0 mg
n=8 Participants
|
Morphine 15 mg
n=8 Participants
|
Morphine 30 mg
n=8 Participants
|
Buprenorphine 8 mg
n=8 Participants
|
Buprenorphine 16 mg
n=8 Participants
|
Buprenorphine 32 mg
n=8 Participants
|
Buprenorphine 48 mg
n=8 Participants
|
Buprenorphine 60 mg
n=8 Participants
|
|---|---|---|---|---|---|---|---|---|
|
Psychomotor/Cognitive Performance Effects Assessed by Trails B
|
1.58 minutes
Standard Deviation 0.84
|
1.51 minutes
Standard Deviation 0.82
|
1.68 minutes
Standard Deviation 1.15
|
1.57 minutes
Standard Deviation 0.66
|
1.85 minutes
Standard Deviation 1.39
|
1.42 minutes
Standard Deviation 0.39
|
1.49 minutes
Standard Deviation 0.53
|
1.46 minutes
Standard Deviation 0.50
|
PRIMARY outcome
Timeframe: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)Population: Subjects who completed all test conditions.
Outcome measures
| Measure |
Placebo 0 mg
n=8 Participants
|
Morphine 15 mg
n=8 Participants
|
Morphine 30 mg
n=8 Participants
|
Buprenorphine 8 mg
n=8 Participants
|
Buprenorphine 16 mg
n=8 Participants
|
Buprenorphine 32 mg
n=8 Participants
|
Buprenorphine 48 mg
n=8 Participants
|
Buprenorphine 60 mg
n=8 Participants
|
|---|---|---|---|---|---|---|---|---|
|
Physiologic Effects as Assessed by Blood Pressure
Systolic Blood Pressure
|
114.11 mmHg
Standard Deviation 8.82
|
114.71 mmHg
Standard Deviation 10.34
|
119.21 mmHg
Standard Deviation 10.85
|
118.59 mmHg
Standard Deviation 15.15
|
111.42 mmHg
Standard Deviation 9.43
|
114.11 mmHg
Standard Deviation 14.84
|
119.18 mmHg
Standard Deviation 12.48
|
116.77 mmHg
Standard Deviation 11.90
|
|
Physiologic Effects as Assessed by Blood Pressure
Diastolic Blood Pressure
|
63.85 mmHg
Standard Deviation 7.13
|
64.92 mmHg
Standard Deviation 8.18
|
66.72 mmHg
Standard Deviation 8.08
|
67.35 mmHg
Standard Deviation 7.62
|
61.82 mmHg
Standard Deviation 6.96
|
62.60 mmHg
Standard Deviation 9.33
|
65.73 mmHg
Standard Deviation 7.29
|
64.39 mmHg
Standard Deviation 7.02
|
PRIMARY outcome
Timeframe: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)Population: Subjects who completed all test conditions.
Outcome measures
| Measure |
Placebo 0 mg
n=8 Participants
|
Morphine 15 mg
n=8 Participants
|
Morphine 30 mg
n=8 Participants
|
Buprenorphine 8 mg
n=8 Participants
|
Buprenorphine 16 mg
n=8 Participants
|
Buprenorphine 32 mg
n=8 Participants
|
Buprenorphine 48 mg
n=8 Participants
|
Buprenorphine 60 mg
n=8 Participants
|
|---|---|---|---|---|---|---|---|---|
|
Physiologic Effects as Assessed by Heart Rate
|
70.44 beats/min
Standard Deviation 7.56
|
70.56 beats/min
Standard Deviation 6.04
|
69.80 beats/min
Standard Deviation 8.19
|
71.22 beats/min
Standard Deviation 9.61
|
69.41 beats/min
Standard Deviation 8.19
|
66.44 beats/min
Standard Deviation 10.20
|
69.06 beats/min
Standard Deviation 6.86
|
67.51 beats/min
Standard Deviation 8.24
|
PRIMARY outcome
Timeframe: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)Population: Subjects who completed all test conditions.
Outcome measures
| Measure |
Placebo 0 mg
n=8 Participants
|
Morphine 15 mg
n=8 Participants
|
Morphine 30 mg
n=8 Participants
|
Buprenorphine 8 mg
n=8 Participants
|
Buprenorphine 16 mg
n=8 Participants
|
Buprenorphine 32 mg
n=8 Participants
|
Buprenorphine 48 mg
n=8 Participants
|
Buprenorphine 60 mg
n=8 Participants
|
|---|---|---|---|---|---|---|---|---|
|
Physiologic Effects as Assessed by Body Temperature
|
85.99 Degrees Fahrenheit
Standard Deviation 5.41
|
87.43 Degrees Fahrenheit
Standard Deviation 4.82
|
89.20 Degrees Fahrenheit
Standard Deviation 3.91
|
89.76 Degrees Fahrenheit
Standard Deviation 4.30
|
90.33 Degrees Fahrenheit
Standard Deviation 3.84
|
89.11 Degrees Fahrenheit
Standard Deviation 4.12
|
90.22 Degrees Fahrenheit
Standard Deviation 4.25
|
90.62 Degrees Fahrenheit
Standard Deviation 4.44
|
PRIMARY outcome
Timeframe: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)Population: Subjects who completed all test conditions.
Outcome measures
| Measure |
Placebo 0 mg
n=8 Participants
|
Morphine 15 mg
n=8 Participants
|
Morphine 30 mg
n=8 Participants
|
Buprenorphine 8 mg
n=8 Participants
|
Buprenorphine 16 mg
n=8 Participants
|
Buprenorphine 32 mg
n=8 Participants
|
Buprenorphine 48 mg
n=8 Participants
|
Buprenorphine 60 mg
n=8 Participants
|
|---|---|---|---|---|---|---|---|---|
|
Physiologic Effects as Assessed by Oxygen Saturation
|
97.81 percentage of saturated hemoglobin
Standard Deviation 0.77
|
97.57 percentage of saturated hemoglobin
Standard Deviation .80
|
97.15 percentage of saturated hemoglobin
Standard Deviation 0.84
|
96.94 percentage of saturated hemoglobin
Standard Deviation 0.96
|
96.73 percentage of saturated hemoglobin
Standard Deviation 1.07
|
96.37 percentage of saturated hemoglobin
Standard Deviation 1.61
|
96.75 percentage of saturated hemoglobin
Standard Deviation 1.30
|
96.49 percentage of saturated hemoglobin
Standard Deviation 1.62
|
PRIMARY outcome
Timeframe: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)Population: Subjects who completed all test conditions.
Outcome measures
| Measure |
Placebo 0 mg
n=8 Participants
|
Morphine 15 mg
n=8 Participants
|
Morphine 30 mg
n=8 Participants
|
Buprenorphine 8 mg
n=8 Participants
|
Buprenorphine 16 mg
n=8 Participants
|
Buprenorphine 32 mg
n=8 Participants
|
Buprenorphine 48 mg
n=8 Participants
|
Buprenorphine 60 mg
n=8 Participants
|
|---|---|---|---|---|---|---|---|---|
|
Physiologic Effects as Assessed by Pupil Diameter
|
4.00 millimeters
Standard Deviation 1.31
|
3.33 millimeters
Standard Deviation 0.87
|
2.74 millimeters
Standard Deviation 0.83
|
2.87 millimeters
Standard Deviation 1.19
|
2.73 millimeters
Standard Deviation 0.84
|
2.63 millimeters
Standard Deviation 0.79
|
2.61 millimeters
Standard Deviation 1.02
|
2.64 millimeters
Standard Deviation 0.99
|
Adverse Events
Placebo Intervention
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Morphine Intervention
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Buprenorphine Intervention
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Eric C. Strain, M.D.
Johns Hopkins University School of Medicine
Phone: 410-550-1191
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place