Evaluation of Long-term Buprenorphine Plasma Exposure

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.

• Blood sample collection (Diagnostic test): Determination of buprenorphine and norbuprenorphine plasma 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

Primary outcomes

• Qualitative Urinary Drug Screen (UDS) for Buprenorphine in Parts A + B [Days 1, 30, 60]: 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.
• Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B [Days 1, 30, 60]: 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.
• Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B [Days 1, 30, 60]: 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.
• Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B [Days 1, 30, 60]: 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.

Sex: All

Inclusion Criteria:

* Participated in Study RB-US-13-0003 or both Studies RB-US-13-0003 and INDV-6000-301 and received at least 2 subcutaneous (SC) injections of SUBLOCADE
* Within 12 to 36 months post his or her last SUBLOCADE injection at the time of the Screening Visit
* Female individuals of childbearing potential must agree to have a pregnancy test administered prior to enrollment and throughout the study. Pregnancy does not prohibit participation
* Willing to adhere to study procedures and provide written informed consent prior to the start of any study procedures.

Exclusion Criteria:

* Received SUBLOCADE or any other long-acting buprenorphine product at any time after ending their participation in Study RB-US-13-0003 or Study INDV-6000-301
* Taken any buprenorphine (prescribed or illicit) within 3 weeks prior to the Screening visit (study Part A, Visit 1)

Participant flow

Outcome results

• Qualitative Urinary Drug Screen (UDS) for Buprenorphine in Parts A + B (Primary), Count of participants, Participants: Part A Cohort: Visit 1 27; Part B Cohort: Visit 1 19; Part B Cohort: Visit 2 16; Part B Cohort: Visit 3 15
• Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B (Primary), Count of participants, Participants: Part A Cohort: Visit 1 31; Part B Cohort: Visit 1 23; Part B Cohort: Visit 2 19; Part B Cohort: Visit 3 17
• Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B (Primary), Count of participants, Participants: Part A Cohort: Visit 1 30; Part B Cohort: Visit 1 19; Part B Cohort: Visit 2 17; Part B Cohort: Visit 3 17
• Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B (Primary), Count of participants, Participants: Part A Cohort: Visit 1 32; Part B Cohort: Visit 1 20; Part B Cohort: Visit 2 18; Part B Cohort: Visit 3 16

Adverse events

Time frame: Day 1 to Day 60

• Study Protocol (PDF, 2019-04-22)
• Statistical Analysis Plan (PDF, 2019-05-22)