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The study objective is to characterise the long-term plasma exposure to buprenorphine after stopping SUBLOCADE treatment. There are no interventions planned.
This multicentre investigation will enroll participants from Study RB-US-13-0003 (NCT02510014) or both Studies RB-US-13-0003 and INDV-6000-301 (NCT02896296) and who received at least 2 subcutaneous (SC) injections of SUBLOCADE.
There are two parts to the study:
Part A consists of a single visit during which urine samples are collected to measure free buprenorphine and free norbuprenorphine concentrations; qualitative urine drug samples (UDS) for opioids, including buprenorphine; quantitative UDS for buprenorphine, norbuprenorphine and naloxone; and determination of creatinine concentration. Blood samples are collected for the determination of buprenorphine and norbuprenorphine plasma concentrations.
Results on the quantitative UDS performed in Part A determine enrollment in Part B: participants who provide a quantifiable (i.e., positive) result for buprenorphine and/or norbuprenorphine and a non-quantifiable (i.e., negative) result for naloxone meet continuation criteria to move on to Part B if Part B is still open to enrolment. Part B consists of two visits 30 days apart in which the same tests are run as were done in Part A.
Data indicate that after discontinuing SUBLOCADE patients may have detectable concentrations of buprenorphine in plasma and urine for 12 months or longer. Previous Phase II/III studies did not evaluate the pharmacokinetics (PK) of buprenorphine beyond 2 months after the last injection; this study will characterize the long-term plasma exposure starting at least 12 months after the last injection. The study will also assess relationships between plasma drug concentrations, free drug concentrations in urine and urine drug screen (UDS) results in order to provide refined guidance to patients and physicians with respect to long-term exposure to buprenorphine after stopping SUBLOCADE treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A Cohort | 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 | 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 (Visits 2 and 3) which are conducted approximately 30 days apart during which blood and urine samples are collected. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood sample collection | Diagnostic Test | Determination of buprenorphine and norbuprenorphine plasma concentrations |
|
| Measure | Description | Time Frame |
|---|---|---|
| Qualitative Urinary Drug Screen (UDS) for Buprenorphine in Parts A + B | 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 (SUBLOCADEâ„¢) was 22 - 38 months prior during previous phase III studies. | Days 1, 30, 60 |
| Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B | 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 (SUBLOCADEâ„¢) was 22 - 38 months prior during previous phase III studies. | Days 1, 30, 60 |
| Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B | 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 (SUBLOCADEâ„¢) was 22 - 38 months prior during previous phase III studies. |
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Inclusion Criteria:
Exclusion Criteria:
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Subjects who participated in either of the studies listed above and who received their last SUBLOCADE injection within 12 to 30 months of the Screening visit. A maximum of 30 subjects may continue to Part B and will return for 2 additional visits 30 days apart.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pathway Healthcare | Hamilton | Alabama | 35570 | United States | ||
| Meridian Research |
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54 subjects were screened. One did not meet eligibility criteria.
All investigators sites were in the U.S.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A |
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| Part B |
|
Safety Analysis Set
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Qualitative Urinary Drug Screen (UDS) for Buprenorphine in Parts A + B | 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 (SUBLOCADEâ„¢) was 22 - 38 months prior during previous phase III studies. | 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. | Posted | Count of Participants | Participants | Days 1, 30, 60 |
|
Day 1 to Day 60
Only adverse events (AEs) associated with study assessments and/or study conduct were collected.
Since there is no study drug for this study, no treatment emergent AE is defined for this study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Director, Clinical Development | Indivior, Inc. | 804-379-1090 | Robert.Dobbins@Indivior.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 22, 2019 | Jul 13, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 22, 2019 | Jul 13, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009293 | Opioid-Related Disorders |
| ID | Term |
|---|---|
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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PK plasma samples to assess buprenorphine concentrations
| Urine sample collection | Diagnostic Test | Urine sample for determination of free buprenorphine and free norbuprenorphine concentrations, qualitative UDS for opioids, quantitative UDS for buprenorphine, norbuprenorphine and naloxone, and determination of creatinine concentration |
|
| Days 1, 30, 60 |
| Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B | 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 (SUBLOCADEâ„¢) was 22 - 38 months prior during previous phase III studies. | Days 1, 30, 60 |
| Tampa |
| Florida |
| 33606 |
| United States |
| Phoenix Medical Research | Prairie Village | Kansas | 66208 | United States |
| Adams Clinical | Watertown | Massachusetts | 02472 | United States |
| Hassman Research Institute | Berlin | New Jersey | 08009 | United States |
| Neurobehavioral Clinical Research | North Canton | Ohio | 44720 | United States |
| Pahl Research | Oklahoma City | Oklahoma | 73112 | United States |
| SP Research | Oklahoma City | Oklahoma | 73112 | United States |
| CODA | Portland | Oregon | 97232 | United States |
| Clinical Research Associates of Central PA, LLC | Altoona | Pennsylvania | 16602 | United States |
| Pillar Research | Richardson | Texas | 75080 | United States |
|
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Body Mass Index Group | Count of Participants | Participants |
|
| Part A Cohort: Visit 1 |
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. |
| OG001 | Part B Cohort: Visit 1 | 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. |
| OG002 | Part B Cohort: Visit 2 | 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. |
| OG003 | Part B Cohort: Visit 3 | 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. |
|
|
| Primary | Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B | 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 (SUBLOCADEâ„¢) was 22 - 38 months prior during previous phase III studies. | 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. | Posted | Count of Participants | Participants | Days 1, 30, 60 |
|
|
|
| Primary | Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B | 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 (SUBLOCADEâ„¢) was 22 - 38 months prior during previous phase III studies. | 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. | Posted | Count of Participants | Participants | Days 1, 30, 60 |
|
|
|
| Primary | Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B | 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 (SUBLOCADEâ„¢) was 22 - 38 months prior during previous phase III studies. | 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. | Posted | Count of Participants | Participants | Days 1, 30, 60 |
|
|
|
| 0 |
| 53 |
| 0 |
| 53 |
| 0 |
| 53 |
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.
| Buprenorphine - Negative |
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| Buprenorphine - Not Available |
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| Norbuprenorphine - Positive |
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| Norbuprenorphine - Negative |
|
| Norbuprenorphine- Not Available |
|
| Bup + Nor - Positive |
|
| Bup + Nor - Negative |
|
| Bup + Nor - Not Available |
|
| Buprenorphine - Negative |
|
| Buprenorphine - Not Available |
|
| Norbuprenorphine - Positive |
|
| Norbuprenorphine - Negative |
|
| Norbuprenorphine- Not Available |
|
| Bup + Nor - Positive |
|
| Bup + Nor - Negative |
|
| Bup + Nor - Not Available |
|
| Buprenorphine - Negative |
|
| Buprenorphine - Not Available |
|
| Norbuprenorphine - Positive |
|
| Norbuprenorphine - Negative |
|
| Norbuprenorphine- Not Available |
|
| Bup + Nor - Positive |
|
| Bup + Nor - Negative |
|
| Bup + Nor - Not Available |
|