Trial Outcomes & Findings for Discontinuation From Chronic Opioid Therapy For Pain Using a Buprenorphine Taper (NCT NCT02737826)

NCT ID: NCT02737826

Last Updated: 2022-12-01

Results Overview

For Phase I, the primary outcome measure is the percentage of patients who tolerate buprenorphine initiation within an 8-hour initiation period, as evidenced by a total score of 3 points when summing the following measures (1) moderate-good level of pain control (same or improved rating on a 0-10 visual analogue scale for pain) = 1 point, (2) mild to no withdrawal symptoms (≤10 on the Subjective Opioid Withdrawal Scale) = 1 point, and (3) willingness to continue to the stabilization and tapering phase of the study; "yes" = 1 point.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 32 participants
• Primary outcome timeframe: 8 hours post dose
• Results posted on: 2022-12-01

Participant Flow

Participant milestones

Measure	Phase II - Gabapentin + Buprenorphine Taper Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, 2 week stabilization period where buprenorphine will be titrated up as tolerated/needed to a maximum of 24 mg/day and gabapentin will be titrated up to 1600mg/day in 3 daily doses as tolerated. After the 2 week stabilization period, buprenorphine tapering will begin according to a tapering schedule that will last up to 8 weeks based on stabilizing buprenorphine dose. After the buprenorphine taper is complete, a 1 week taper of gabapentin will be provided.	Phase II - Placebo + Buprenorphine Taper Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, 2 week stabilization period where buprenorphine will be titrated up as tolerated/needed to a maximum of 24 mg/day and placebo will be titrated up to 1600mg/day in 3 daily doses as tolerated. After the 2 week stabilization period, buprenorphine tapering will begin according to a tapering schedule that will last up to 8 weeks based on stabilizing buprenorphine dose. After the buprenorphine taper is complete, a 1 week taper of placebo will be provided.	Phase I - Buprenorphine Initiation In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol using up to 16mg of buprenoprhine over an up to 8 hour induction window. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.
Phase I - Buprenorphine Initiation STARTED	0	0	27
Phase I - Buprenorphine Initiation COMPLETED	0	0	27
Phase I - Buprenorphine Initiation NOT COMPLETED	0	0	0
Phase II - Randomization + Taper STARTED	13	14	0
Phase II - Randomization + Taper COMPLETED	1	0	0
Phase II - Randomization + Taper NOT COMPLETED	12	14	0

Reasons for withdrawal

Measure	Phase II - Gabapentin + Buprenorphine Taper Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, 2 week stabilization period where buprenorphine will be titrated up as tolerated/needed to a maximum of 24 mg/day and gabapentin will be titrated up to 1600mg/day in 3 daily doses as tolerated. After the 2 week stabilization period, buprenorphine tapering will begin according to a tapering schedule that will last up to 8 weeks based on stabilizing buprenorphine dose. After the buprenorphine taper is complete, a 1 week taper of gabapentin will be provided.	Phase II - Placebo + Buprenorphine Taper Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, 2 week stabilization period where buprenorphine will be titrated up as tolerated/needed to a maximum of 24 mg/day and placebo will be titrated up to 1600mg/day in 3 daily doses as tolerated. After the 2 week stabilization period, buprenorphine tapering will begin according to a tapering schedule that will last up to 8 weeks based on stabilizing buprenorphine dose. After the buprenorphine taper is complete, a 1 week taper of placebo will be provided.	Phase I - Buprenorphine Initiation In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol using up to 16mg of buprenoprhine over an up to 8 hour induction window. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.
Phase II - Randomization + Taper Withdrawal by Subject	12	14	0

Baseline Characteristics

Discontinuation From Chronic Opioid Therapy For Pain Using a Buprenorphine Taper

Baseline characteristics by cohort

Measure	All Study Participants n=27 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.
Age, Continuous	54.48 years STANDARD_DEVIATION 11.11 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	27 participants n=5 Participants

PRIMARY outcome

Timeframe: 8 hours post dose

For Phase I, the primary outcome measure is the percentage of patients who tolerate buprenorphine initiation within an 8-hour initiation period, as evidenced by a total score of 3 points when summing the following measures (1) moderate-good level of pain control (same or improved rating on a 0-10 visual analogue scale for pain) = 1 point, (2) mild to no withdrawal symptoms (≤10 on the Subjective Opioid Withdrawal Scale) = 1 point, and (3) willingness to continue to the stabilization and tapering phase of the study; "yes" = 1 point.

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=27 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Percentage of Patients Who Tolerate Buprenorphine Initiation	27 Participants	—

PRIMARY outcome

Timeframe: 8 weeks after stabilization at Week 10

For Phase II, the primary outcome measure will be number of participants opioid who achieve cessation 8 weeks after stabilization at Week 10, evidenced as a score of 3 points when summing the following measures: self-report of no opioid use = 1 point; prescription drug monitoring data showing no opioid prescriptions filled in past 30 days = 1 point; and confirmatory negative urine toxicology for a full panel of opioids = 1 point.

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=13 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper n=14 Participants Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Number of Participants Who Achieve Opioid Cessation	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 1 month post-taper

Population: Only one person in the Gabapentin + Buprenorphine Taper Arm completed the 8 week study buprenorphine taper, making them eligible for analysis for this secondary outcome measure. Zero people in the Placebo + Buprenorphne Taper Arm completed the study buprenorphine taper.

Opioid cessation post taper: 1 month with opioid cessation measured through self-report, prescription drug monitoring data, and confirmatory UDS for a full panel of opioids.

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=1 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Number of Participants Who Achieve Opioid Cessation Post-taper: 1 Month	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline

Population: One consented and randomized participant in the Placebo + Buprenorphine Taper Arm was erroneously randomized prior to buprenorphine induction, and dropped out of the study on the day of induction prior to receiving first buprenorphine dose (prior to eligibility for randomization). This participant is not included in this analysis.

The Self Reporting Pain Catastrophizing scale consists of 13 items scored from 0 to 4. The total possible score is 52. A higher score indicates more catastrophizing thoughts are present. A lower score indicates less catastrophizing thoughts.

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=13 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper n=13 Participants Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Pain Self-report: Pain Catastrophizing Scale - Baseline	21.9 units on a scale Interval 3.0 to 39.0	21.2 units on a scale Interval 0.0 to 48.0

SECONDARY outcome

Timeframe: Baseline

Population: One person was erroneously randomized to placebo before they were eligible for randomization and dropped out prior to induction, so they are not considered in this analysis.

Mechanical (Pressure) Pain Threshold Assessment (PPTh): A digital anesthesiometer (IITC Life Sciences ElectroVonFrey) will be used to assess mechanical pain perception. Pain threshold to static mechanical stimuli will be determined by applying the rigid monofilament to the dorsum of each subject's right hand with increasing pressure (10 grams per second) until the participant indicates verbally that the pain threshold has been reached.

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=13 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper n=13 Participants Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Pain Laboratory Testing: Mechanical - Baseline	284.2 grams per second Interval 113.7 to 482.7	289.1 grams per second Interval 163.6 to 627.3

SECONDARY outcome

Timeframe: Baseline

Population: One person erroneously randomized to placebo before eligible for induction and who never completed buprenorphine induction not considered in this analysis.

COMM is a 17 item questionnaire that is used to examine concurrent misuse. The score range is from 0-28. A lower score represents participant showing less aberrant behaviors associates with misuse of option medications, and a higher score represents more aberrant behaviors associated with opioid medical misuse.

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=13 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper n=13 Participants Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Mean Score of Current Opioid Measure (COMM)	16 units on a scale Interval 1.0 to 41.0	15 units on a scale Interval 5.0 to 49.0

SECONDARY outcome

Timeframe: baseline

Population: This form was introduced after the first 2 participants had been randomized, so we only have this data for the 24 who were randomized after buprenorphine induction (vs n=26 for other outcome measures). One person was erroneously randomized prior to eligibility for randomization and was not included in calculations for these secondary outcomes.

The Mean score of Physical Function on PROMIS short form. The global physical health score is a sum of responses to 4 questions. The range is from 4-20. A lower score represents lower physical function.

The following questions will be asked: In general, how would you rate your physical health? (range is 1-5; 1 represents poor rating in health, 5 represents excellent rating of physical health) To what extent are you able to carry out your everyday physical activities such as walking, climbing stairs, carrying groceries, or moving a chair? (range is 1-5; 1 represents score of not at all, 5 represents score of completely) How would you rate your fatigue on average? (range is 1-5; 1 represents very severe fatigue, and 5 represents no fatigue) How would you rate your pain on average (range is 0-10; 0 represents no pain, 10 represents worst pain imaginable). The pain score is then recoded: 0, no pain = 5; 1, 2, or 3 = 4; 4, 5, or 6 =3; 7, 8, 9 =2;10 =1

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=12 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper n=12 Participants Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Mean Score of PROMIS Physical Function Short Form (PROMIS SF 10) - RAW SCORE PH	10.3 units on a scale Interval 8.0 to 14.0	11 units on a scale Interval 7.0 to 14.0

SECONDARY outcome

Timeframe: baseline

Population: One person erroneously randomized not included

The PSQI is a 19 item self-report questionnaire that assesses sleep quality over a 1-month time interval. The measure consists of 19 individual items, creating 7 components (time gone to bed, how long it takes to go to sleep, wake up time, hours slept, issues sleeping, total hours slept etc.) that produce one global score. Each item is weighted on a 0-3 interval scale. The global score is calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, A lower scale is indicative of better sleep quality and higher score represents poor sleep quality.

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=13 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper n=13 Participants Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Mean Score Pittsburgh Sleep Quality Index	12.5 units on a scale Interval 4.0 to 19.0	10.6 units on a scale Interval 4.0 to 16.0

SECONDARY outcome

Timeframe: baseline

The Subjective Opiate Withdrawal Scale (SOWS) consist of 16 symptoms rated in intensity by patients on a 5-point scale of intensity as follows: 0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely. The total score is a sum of item ratings, and ranges from 0 to 64.

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=13 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper n=13 Participants Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Mean Score of Subjective Opioid Withdrawal Scale (SOWS)	17.3 units on a scale Interval 0.0 to 58.0	11.9 units on a scale Interval 0.0 to 49.0

SECONDARY outcome

Timeframe: Post-taper - 3 months

Population: One person in the Gabapentin + Buprenorphine Taper Arm completed the study buprenorphine taper and were eligible for analysis. Zero persons in the Placebo + Buprenorphine Taper Arm completed the study buprenoprhine taper and were eligible for analysis.

Opioid cessation is evidenced as a score of 3 points when summing the following measures: self-report of no opioid use = 1 point; prescription drug monitoring data showing no opioid prescriptions filled in past 30 days = 1 point; and confirmatory negative urine toxicology for a full panel of opioids = 1 point.

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=1 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Number of Participants Who Achieved Opioid Cessation Post-taper - 3 Months	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Post-taper - 6 months

Population: One person in the Gabapentin + Buprenorphine Taper Arm completed the study buprenorphine taper, and zero persons in the Placebo + Buprenorphine Taper Arm completed the study buprenorphine taper.

Opioid cessation is evidenced as a score of 3 points when summing the following measures: self-report of no opioid use = 1 point; prescription drug monitoring data showing no opioid prescriptions filled in past 30 days = 1 point; and confirmatory negative urine toxicology for a full panel of opioids = 1 point.

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=1 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Number of Participants Who Achieved Opioid Cessation Post-taper - 6 Months	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Post-taper - 12 months

Population: One person in the Gabapentin + Buprenorphine Taper Arm and Zero people in the Placebo + Buprenorphine Taper Arm completed the study buprenorphine taper.

Opioid cessation is evidenced as a score of 3 points when summing the following measures: self-report of no opioid use = 1 point; prescription drug monitoring data showing no opioid prescriptions filled in past 30 days = 1 point; and confirmatory negative urine toxicology for a full panel of opioids = 1 point.

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=1 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Number of Participants Who Achieved Opioid Cessation Post-taper - 12 Months	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline

Population: One person was erroneously randomized to placebo before eligible for randomization, and never completed buprenorphine induction, so they are not considered in this analysis.

DNIC will be measured as the percent change in PPTh during the cold pressor tasks relative to baseline. A percent increase represents normal functioning of pain inhibitory processes.

Outcome measures

Measure	Phase I - Buprenorphine Initiation n=13 Participants In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. "Buprenorphine tolerability" will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol.	Phase II - Placebo + Buprenorphine Taper n=13 Participants Subjects who tolerate buprenorphine initiation in Phase I (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Buprenorphine - Phase I: In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol. Gabapentin - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering. Placebo - Phase II: Subjects who tolerate buprenorphine initiation (determined by pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper) will proceed to Phase II, which will involve randomization to gabapentin or placebo, buprenorphine stabilization, and buprenorphine tapering.
Pain Laboratory Measures - Descending Noxious Inhibitory Control (DNIC) - Average, Baseline	312.5 percentage of change Interval 139.5 to 538.7	326.4 percentage of change Interval 178.8 to 631.3

Adverse Events

Phase I - Buprenorphine Initiation

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Phase II - Gabapentin + Buprenorphine

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Phase II - Gabapentin + Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Phase II - Buprenorphine Taper

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Phase I - Buprenorphine Initiation n=27 participants at risk In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol up to 16mg sublingually over an 8 hour induction window.	Phase II - Gabapentin + Buprenorphine n=13 participants at risk Subjects who tolerate sublingual buprenorphine initiation in Phase I will proceed to Phase II, which will involve randomization to oral gabapentin or placebo, 2 week stabilization period, and up to 8 week buprenorphine tapering period. Those randomized to gabapentin will receive up to 1600mg gabapentin (double blinded) divided three times daily, titrated over the 2 week stabilization period and continued during the buprenorphine tapering period. During the 2 week stabilization period, buprenorphine will also be titrated up to 24mg as needed/tolerated.	Phase II - Gabapentin + Placebo n=14 participants at risk Subjects who tolerate sublingual buprenorphine initiation in Phase I will proceed to Phase II, which will involve randomization to oral gabapentin or placebo, 2 week stabilization period, and up to 8 week buprenorphine tapering period. Those randomized to placebo will receive up to 1600mg placebo (double blinded) divided three times daily, titrated over the 2 week stabilization period and continued during the buprenorphine tapering period. During the 2 week stabilization period, buprenorphine will also be titrated up to 24mg as needed/tolerated.	Phase II - Buprenorphine Taper n=27 participants at risk After a 2 week stabilization period where sublingual buprenorphine is titrated up to 24 mg/day and oral gabapentin/placebo is titrated up to 1600mg/day, subjects will enter a buprenorphine tapering period lasting up to 8 weeks. The suggested buprenorphine taper will be determined by stabilizing dose, but able to be altered by prescriber or participant based on symptoms.
Musculoskeletal and connective tissue disorders Increased Pain	0.00% 0/27 • 12 months	30.8% 4/13 • Number of events 7 • 12 months	35.7% 5/14 • Number of events 9 • 12 months	0.00% 0/27 • 12 months
Gastrointestinal disorders Nausea	7.4% 2/27 • Number of events 2 • 12 months	30.8% 4/13 • Number of events 8 • 12 months	28.6% 4/14 • Number of events 7 • 12 months	0.00% 0/27 • 12 months
General disorders Dry Mouth	0.00% 0/27 • 12 months	23.1% 3/13 • Number of events 5 • 12 months	28.6% 4/14 • Number of events 6 • 12 months	0.00% 0/27 • 12 months
Blood and lymphatic system disorders Lower extremity swelling	0.00% 0/27 • 12 months	15.4% 2/13 • Number of events 4 • 12 months	42.9% 6/14 • Number of events 7 • 12 months	0.00% 0/27 • 12 months
General disorders Insomnia	0.00% 0/27 • 12 months	23.1% 3/13 • Number of events 5 • 12 months	28.6% 4/14 • Number of events 8 • 12 months	0.00% 0/27 • 12 months
Gastrointestinal disorders Vomiting	0.00% 0/27 • 12 months	30.8% 4/13 • Number of events 7 • 12 months	14.3% 2/14 • Number of events 4 • 12 months	0.00% 0/27 • 12 months
Nervous system disorders Muscle twitching/spasm	0.00% 0/27 • 12 months	23.1% 3/13 • Number of events 3 • 12 months	21.4% 3/14 • Number of events 3 • 12 months	0.00% 0/27 • 12 months
Gastrointestinal disorders Constipation	0.00% 0/27 • 12 months	15.4% 2/13 • Number of events 2 • 12 months	21.4% 3/14 • Number of events 5 • 12 months	0.00% 0/27 • 12 months
General disorders Sedation/sleepiness	7.4% 2/27 • Number of events 2 • 12 months	30.8% 4/13 • Number of events 6 • 12 months	14.3% 2/14 • Number of events 4 • 12 months	0.00% 0/27 • 12 months

Additional Information

Dr. Kelly Barth

Medical University of South Carolina

Phone: 843-792-0686

Email: stephen@musc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place