Trial Outcomes & Findings for Evaluation of Long-term Buprenorphine Plasma Exposure (NCT NCT03752528)
NCT ID: NCT03752528
Last Updated: 2020-08-21
Results Overview
The qualitative UDS (immunoassay) is the primary test used for the initial screening for opioids in patients in clinical practice. It provides only a qualitative assessment of buprenorphine exposure (i.e., positive or negative) with a low limit of quantification (LLOQ) of 5 ng/mL. The qualitative UDS is reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3). Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.
COMPLETED
53 participants
Days 1, 30, 60
2020-08-21
Participant Flow
All investigators sites were in the U.S.
54 subjects were screened. One did not meet eligibility criteria.
Participant milestones
| Measure |
All Study Participants
All study participants who enrolled into the Part A Cohort. These participants previously participated in study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 and who received at least 2 doses of SUBLOCADE 12-36 months prior. Some of the participants continued into study Part B after completing Part A.
|
|---|---|
|
Part A
STARTED
|
53
|
|
Part A
COMPLETED
|
51
|
|
Part A
NOT COMPLETED
|
2
|
|
Part B
STARTED
|
24
|
|
Part B
COMPLETED
|
20
|
|
Part B
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
All Study Participants
All study participants who enrolled into the Part A Cohort. These participants previously participated in study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 and who received at least 2 doses of SUBLOCADE 12-36 months prior. Some of the participants continued into study Part B after completing Part A.
|
|---|---|
|
Part A
Lost to Follow-up
|
1
|
|
Part A
Protocol Violation
|
1
|
|
Part B
Protocol Violation
|
1
|
|
Part B
Study terminated by sponsor
|
3
|
Baseline Characteristics
Evaluation of Long-term Buprenorphine Plasma Exposure
Baseline characteristics by cohort
| Measure |
All Study Participants
n=53 Participants
All study participants who enrolled into the Part A Cohort. These participants previously participated in study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 and who received at least 2 doses of SUBLOCADE 12-36 months prior. Some of the participants continued into study Part B after completing Part A.
|
|---|---|
|
Age, Continuous
|
43.0 years
STANDARD_DEVIATION 11.46 • n=99 Participants
|
|
Age, Customized
18 - 44 years
|
32 Participants
n=99 Participants
|
|
Age, Customized
45 - 64 years
|
19 Participants
n=99 Participants
|
|
Age, Customized
.>= 65 years
|
2 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
50 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
16 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
37 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
53 participants
n=99 Participants
|
|
Weight
|
79.7 kg
STANDARD_DEVIATION 18.51 • n=99 Participants
|
|
Body Mass Index
|
26.5 kg/m^2
STANDARD_DEVIATION 5.58 • n=99 Participants
|
|
Body Mass Index Group
< 18.5 kg/m^2
|
1 Participants
n=99 Participants
|
|
Body Mass Index Group
>= 18.5 and < 25 kg/m^2
|
24 Participants
n=99 Participants
|
|
Body Mass Index Group
>= 25 and < 30 kg/m^2
|
15 Participants
n=99 Participants
|
|
Body Mass Index Group
>= 30 kg/m^2
|
13 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Days 1, 30, 60Population: Full analysis set includes participants who have at least one measure of buprenorphine or norbuprenorphine concentration in plasma or in urine in Part A. Four participants who tested positive for naloxone in urine were excluded from summary results. One participant was terminated from the study prior to Part B, Visit 2.
The qualitative UDS (immunoassay) is the primary test used for the initial screening for opioids in patients in clinical practice. It provides only a qualitative assessment of buprenorphine exposure (i.e., positive or negative) with a low limit of quantification (LLOQ) of 5 ng/mL. The qualitative UDS is reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3). Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.
Outcome measures
| Measure |
Part A Cohort: Visit 1
n=49 Participants
Representative data set of participants from study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 who received at least 2 doses of SUBLOCADE 12-36 months prior. Part A consists of a single visit (Visit 1) for both screening and collection of blood and urine samples.
|
Part B Cohort: Visit 1
n=24 Participants
Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 1 results for those participants who continued into Part B of the study.
|
Part B Cohort: Visit 2
n=23 Participants
Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 2 (Day 30) results for those participants who continued into Part B of the study.
|
Part B Cohort: Visit 3
n=20 Participants
Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 3 (Day 60) results for those participants who continued into Part B of the study.
|
|---|---|---|---|---|
|
Qualitative Urinary Drug Screen (UDS) for Buprenorphine in Parts A + B
Positive
|
27 Participants
|
19 Participants
|
16 Participants
|
15 Participants
|
|
Qualitative Urinary Drug Screen (UDS) for Buprenorphine in Parts A + B
Negative
|
22 Participants
|
5 Participants
|
7 Participants
|
5 Participants
|
PRIMARY outcome
Timeframe: Days 1, 30, 60Population: Full analysis set includes participants who have at least one measure of buprenorphine or norbuprenorphine concentration in plasma or in urine in Part A. Four participants who tested positive for naloxone in urine were excluded from summary results. One participant was terminated from the study prior to Part B, Visit 2.
The quantitative UDS measures both buprenorphine and its glucuronide, or both norbuprenorphine and its glucuronide, with an LLOQ of 2 ng/mL. It is typically used by physicians for the confirmation of a positive result on the qualitative UDS. Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3). For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is "Not Available" Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.
Outcome measures
| Measure |
Part A Cohort: Visit 1
n=49 Participants
Representative data set of participants from study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 who received at least 2 doses of SUBLOCADE 12-36 months prior. Part A consists of a single visit (Visit 1) for both screening and collection of blood and urine samples.
|
Part B Cohort: Visit 1
n=24 Participants
Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 1 results for those participants who continued into Part B of the study.
|
Part B Cohort: Visit 2
n=23 Participants
Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 2 (Day 30) results for those participants who continued into Part B of the study.
|
Part B Cohort: Visit 3
n=20 Participants
Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 3 (Day 60) results for those participants who continued into Part B of the study.
|
|---|---|---|---|---|
|
Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B
Buprenorphine - Positive
|
31 Participants
|
23 Participants
|
19 Participants
|
17 Participants
|
|
Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B
Buprenorphine - Negative
|
18 Participants
|
1 Participants
|
4 Participants
|
3 Participants
|
|
Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B
Norbuprenorphine- Not Available
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B
Bup + Nor - Positive
|
32 Participants
|
24 Participants
|
20 Participants
|
18 Participants
|
|
Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B
Buprenorphine - Not Available
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B
Norbuprenorphine - Positive
|
29 Participants
|
21 Participants
|
19 Participants
|
17 Participants
|
|
Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B
Norbuprenorphine - Negative
|
19 Participants
|
2 Participants
|
4 Participants
|
3 Participants
|
|
Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B
Bup + Nor - Negative
|
17 Participants
|
0 Participants
|
3 Participants
|
2 Participants
|
|
Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B
Bup + Nor - Not Available
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Days 1, 30, 60Population: Full analysis set includes participants who have at least one measure of buprenorphine or norbuprenorphine concentration in plasma or in urine in Part A. Four participants who tested positive for naloxone in urine were excluded from summary results. One participant was terminated from the study prior to Part B, Visit 2.
The urine free drug test only measures the "free" buprenorphine and "free" norbuprenorphine (without their glucuronides) with an LLOQ of 0.02 ng/mL. Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3). For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is "Not Available" Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.
Outcome measures
| Measure |
Part A Cohort: Visit 1
n=49 Participants
Representative data set of participants from study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 who received at least 2 doses of SUBLOCADE 12-36 months prior. Part A consists of a single visit (Visit 1) for both screening and collection of blood and urine samples.
|
Part B Cohort: Visit 1
n=24 Participants
Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 1 results for those participants who continued into Part B of the study.
|
Part B Cohort: Visit 2
n=23 Participants
Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 2 (Day 30) results for those participants who continued into Part B of the study.
|
Part B Cohort: Visit 3
n=20 Participants
Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 3 (Day 60) results for those participants who continued into Part B of the study.
|
|---|---|---|---|---|
|
Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Buprenorphine - Negative
|
19 Participants
|
5 Participants
|
5 Participants
|
3 Participants
|
|
Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Norbuprenorphine - Positive
|
46 Participants
|
24 Participants
|
21 Participants
|
20 Participants
|
|
Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Bup + Nor - Positive
|
46 Participants
|
24 Participants
|
21 Participants
|
20 Participants
|
|
Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Bup + Nor - Not Available
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Buprenorphine - Positive
|
30 Participants
|
19 Participants
|
17 Participants
|
17 Participants
|
|
Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Buprenorphine - Not Available
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Norbuprenorphine - Negative
|
3 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Norbuprenorphine- Not Available
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Bup + Nor - Negative
|
3 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Days 1, 30, 60Population: Full analysis set includes participants who have at least one measure of buprenorphine or norbuprenorphine concentration in plasma or in urine in Part A. Four participants who tested positive for naloxone in urine were excluded from summary results. One participant was terminated from the study prior to Part B, Visit 2.
A sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was used to assess the plasma exposure to buprenorphine and norbuprenorphine, its major metabolite. The LLOQ was 0.02 ng/mL for both analytes, which is much lower than the LLOQ of plasma/serum assays conducted by diagnostic laboratories. Data are reported for Part A Cohort (Visit 1) and Part B Cohort (Visits 1, 2 and 3). For Bup+Nor (abbreviation for Buprenorphine + Norbuprenorphine), the result is negative if results for both are negative, the result is positive if either result is positive. If both are missing/not available, or one is negative and the other is missing/not evaluable, the result is "Not Available" Participants' last subcutaneous injections of extended release buprenorphine (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.
Outcome measures
| Measure |
Part A Cohort: Visit 1
n=49 Participants
Representative data set of participants from study RB-US-13-0003 or both studies RB-US-13-0003 and INDV-6000-301 who received at least 2 doses of SUBLOCADE 12-36 months prior. Part A consists of a single visit (Visit 1) for both screening and collection of blood and urine samples.
|
Part B Cohort: Visit 1
n=24 Participants
Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 1 results for those participants who continued into Part B of the study.
|
Part B Cohort: Visit 2
n=23 Participants
Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 2 (Day 30) results for those participants who continued into Part B of the study.
|
Part B Cohort: Visit 3
n=20 Participants
Part A participants with a quantifiable (i.e. positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e. negative) result for naloxone continue in the study for two additional visits (Part B, Visits 2 and 3). This cohort reports Visit 3 (Day 60) results for those participants who continued into Part B of the study.
|
|---|---|---|---|---|
|
Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Norbuprenorphine - Negative
|
27 Participants
|
11 Participants
|
11 Participants
|
8 Participants
|
|
Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Bup + Nor - Positive
|
32 Participants
|
20 Participants
|
18 Participants
|
16 Participants
|
|
Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Bup + Nor - Negative
|
15 Participants
|
3 Participants
|
4 Participants
|
3 Participants
|
|
Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Buprenorphine - Positive
|
32 Participants
|
20 Participants
|
18 Participants
|
16 Participants
|
|
Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Buprenorphine - Negative
|
15 Participants
|
3 Participants
|
4 Participants
|
3 Participants
|
|
Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Buprenorphine - Not Available
|
2 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Norbuprenorphine - Positive
|
20 Participants
|
12 Participants
|
11 Participants
|
11 Participants
|
|
Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Norbuprenorphine- Not Available
|
2 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B
Bup + Nor - Not Available
|
2 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
Adverse Events
All Study Participants
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Proposed publications shall be submitted to Sponsor 30 days prior to submission for publication, and may be withheld for an additional period, up to 90 days, to allow Sponsor to file patent applications. If a multi-center publication isn't submitted for publication within 12 months of the conclusion of the Study at all sites, or is published in a shorter period, the results from the institution's site may be published individually.
- Publication restrictions are in place
Restriction type: OTHER