Evaluation of Long-term Buprenorphine Plasma Exposure

NCT03752528 | Completed Results

• 1 other identifier: INDV-6000-402
• Study Type: observational
• Target: 53
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Opioid-use Disorder

Outcome Measures

Primary Outcomes (4)

• 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 (SUBLOCADE™) 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 (SUBLOCADE™) 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 (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.

  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 (SUBLOCADE™) was 22 - 38 months prior during previous phase III studies.

  Days 1, 30, 60

Study Arms (2)

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.

Diagnostic Test: Blood sample collection; Diagnostic Test: Urine sample collection

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.

Diagnostic Test: Blood sample collection; Diagnostic Test: Urine sample collection

Interventions

Blood sample collection DIAGNOSTIC_TEST

Determination of buprenorphine and norbuprenorphine plasma concentrations

Part A Cohort; Part B Cohort

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

Part A Cohort; Part B Cohort

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Indivior Inc.: lead

Study Sites (11)

Pathway Healthcare

Hamilton, Alabama, 35570, United States

Location

Meridian Research

Tampa, Florida, 33606, United States

Location

Phoenix Medical Research

Prairie Village, Kansas, 66208, United States

Location

Adams Clinical

Watertown, Massachusetts, 02472, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Neurobehavioral Clinical Research

North Canton, Ohio, 44720, United States

Location

Pahl Research

Oklahoma City, Oklahoma, 73112, United States

Location

SP Research

Oklahoma City, Oklahoma, 73112, United States

Location

CODA

Portland, Oregon, 97232, United States

Location

Clinical Research Associates of Central PA, LLC

Altoona, Pennsylvania, 16602, United States

Location

Pillar Research

Richardson, Texas, 75080, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

PK plasma samples to assess buprenorphine concentrations

MeSH Terms

Conditions

Opioid-Related Disorders

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: Global Director, Clinical Development
• Organization: Indivior, Inc.

Robert.Dobbins@Indivior.com

804-379-1090

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2018
• First Posted: November 26, 2018
• Study Start: February 19, 2019
• Primary Completion: July 18, 2019
• Study Completion: July 18, 2019
• Last Updated: August 21, 2020
• Results First Posted: August 3, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)