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Evaluation of Long-term Buprenorphine Plasma Exposure

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ClinicalTrials.gov Identifier: NCT03752528
Recruitment Status : Completed
First Posted : November 26, 2018
Results First Posted : August 3, 2020
Last Update Posted : August 21, 2020
Sponsor:
Information provided by (Responsible Party):
Indivior Inc.

Study Description
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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.


Condition or disease Intervention/treatment
Opioid-use Disorder Diagnostic Test: Blood sample collection Diagnostic Test: Urine sample collection

Detailed Description:
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.
Study Design
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Study Type : Observational
Actual Enrollment : 53 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Evaluation of Long-term Buprenorphine Plasma Exposure in Subjects Who Received at Least 2 Subcutaneous (SC) Injections of Extended-release Buprenorphine (SUBLOCADE™) in Phase III Studies
Actual Study Start Date : February 19, 2019
Actual Primary Completion Date : July 18, 2019
Actual Study Completion Date : July 18, 2019

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
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
Determination of buprenorphine and norbuprenorphine plasma concentrations

Diagnostic Test: Urine sample collection
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 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
Determination of buprenorphine and norbuprenorphine plasma concentrations

Diagnostic Test: Urine sample collection
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


Outcome Measures
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Primary Outcome Measures :
  1. Qualitative Urinary Drug Screen (UDS) for Buprenorphine in Parts A + B [ Time Frame: 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.


  2. Quantitative Urine Drug Screen (UDS) for Buprenorphine and Norbuprenorphine in Parts A + B [ Time Frame: 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.


  3. Urine Free Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B [ Time Frame: 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.


  4. Plasma Drug Test for Buprenorphine and Norbuprenorphine in Parts A + B [ Time Frame: 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.



Biospecimen Retention:   Samples Without DNA
PK plasma samples to assess buprenorphine concentrations

Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03752528


Locations
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United States, Alabama
Pathway Healthcare
Hamilton, Alabama, United States, 35570
United States, Florida
Meridian Research
Tampa, Florida, United States, 33606
United States, Kansas
Phoenix Medical Research
Prairie Village, Kansas, United States, 66208
United States, Massachusetts
Adams Clinical
Watertown, Massachusetts, United States, 02472
United States, New Jersey
Hassman Research Institute
Berlin, New Jersey, United States, 08009
United States, Ohio
Neurobehavioral Clinical Research
North Canton, Ohio, United States, 44720
United States, Oklahoma
Pahl Research
Oklahoma City, Oklahoma, United States, 73112
SP Research
Oklahoma City, Oklahoma, United States, 73112
United States, Oregon
CODA
Portland, Oregon, United States, 97232
United States, Pennsylvania
Clinical Research Associates of Central PA, LLC
Altoona, Pennsylvania, United States, 16602
United States, Texas
Pillar Research
Richardson, Texas, United States, 75080
Sponsors and Collaborators
Indivior Inc.
  Study Documents (Full-Text)

Documents provided by Indivior Inc.:
Study Protocol  [PDF] April 22, 2019
Statistical Analysis Plan  [PDF] May 22, 2019

More Information
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Responsible Party: Indivior Inc.
ClinicalTrials.gov Identifier: NCT03752528    
Other Study ID Numbers: INDV-6000-402
First Posted: November 26, 2018    Key Record Dates
Results First Posted: August 3, 2020
Last Update Posted: August 21, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Opioid-Related Disorders
Narcotic-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders