Monthly Versus Daily Buprenorphine Formulations for Treatment of Opiate Use Disorder

NCT05594121 | Unknown Phase 4

• 1 other identifier: R22-004
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 5

Brief Summary

Opioid use disorder and opioid-related deaths are increasing across Canada. The mainstay of medical treatment includes either full (methadone) or partial (buprenorphine) opioid agonist therapy. In Canada, there are 2 buprenorphine formulations, an immediate-release (Suboxone) and extended-release(Sublocade). These treatments have been shown to be equivalent for medication adherence and treatment retention. However, Sublocade costs 8-times more, and 50% of patients must pay out-of-pocket if they prefer this treatment option. This study is needed to demonstrate the superior benefits of Sublocade on important clinical outcomes to demonstrate its cost-effectiveness and justify expanded insured access across Canada.

Conditions

Moderate to Severe Opioid Use Disorder

Outcome Measures

Primary Outcomes (2)

• Opioid positivity

  Difference in proportions of relapse-free weeks (RFWs) at 12-months from the date of randomization, where relapse-free weeks are defined by the cumulative number of weeks alive during the study period in which there was a negative urine drug screen and negative self-report for non-prescribed opioids. The potential number of RFWs for each patient is the cumulative number of weeks that the patient is alive during the 12-month study period, with a maximum of 48 weeks. A week is defined as a consecutive 7-day period starting on the day of the week that randomization occurred.

  every 7 days for 12 months

• Healthcare utilization

  Difference in incidence rates of healthcare days at 12-months from the date of randomization, where healthcare days represent the number of days alive and registered for an emergency room visit or admitted to an acute care or mental health facility for opioid-related harms or poisonings. For each group, the incidence rate is calculated by dividing the total number of healthcare days by the total person days exposure over the study period. The potential number of healthcare days for each patient is the number of days alive during the 12-month study period, with the maximum being 365 days. Any day in which a patient is documented to have had an emergency room visit or is admitted to an acute care or mental health facility for any opioid-related harm or poisoning will be counted as a healthcare day. Only those healthcare days in which opioid use was considered to be influential to the ER visit or hospitalization will be included in the final analysis.

  12 months

Secondary Outcomes (4)

• Medication Satisfaction

  Every 6 weeks starting on week 6 after randomization for 12 months

• Quality of Life Score

  At time of randomization (baseline), then week 12, week 24 and week 36

• Clinic Retention

  12 months

• Mortality

  12 months

Study Arms (2)

Extended-release subcutaneous buprenorphine (SC-BPN-XR)

EXPERIMENTAL

For eligible patients randomly allocated to SC-BPN-XR, the first dose will be administered at the time of randomization (Day 0). SC-BPN-XR comes in two formulations, 100 mg and 300 mg buprenorphine doses in a pre-filled syringe. SC-BPN-XR administration is by subcutaneous injection in the abdomen. SC-BPN-XR is administered at intervals ≥26 days. For patients randomly allocated to SC-BPN-XR, they will receive the 300 mg dose for the first 2 months, followed by the 100 mg dose every month until the end of the 12-month period. All SC-BPN-XR doses will be administered in clinics by trained personnel. All patients receiving SC-BPN-XR will have their vital signs monitored every 5 minutes for 15 minutes after the injection before leaving the clinic.

Drug: Extended Release Subcutaneous Buprenorphine

Immediate-release sublingual buprenorphine/naloxone (SL-BPN/NX)

ACTIVE COMPARATOR

For eligible patients randomly allocated to SL-BPN/NX, the first study dose will be administered at the time of randomization (Day 0) and will match the SL-BPN/NX type (tablet versus film), route (sublingual versus buccal) and dose used for stabilization prior to study enrollment. For the first 2 weeks of the study period, all SL-BPN/NX administration will be directly observed at community pharmacies by trained personnel according to the usual standard of care. Subsequent to this period, healthcare providers and participants will develop a care plan for ongoing directly observed therapy vs unsupervised take-home dosing according to usual standard of care.

Drug: Immediate Release Sublingual Buprenorphine

Interventions

Extended Release Subcutaneous Buprenorphine DRUG

Monthly subcutaneous injections of long-acting buprenorphine

Also known as: Sublocade

Extended-release subcutaneous buprenorphine (SC-BPN-XR)

Immediate Release Sublingual Buprenorphine DRUG

Daily sublingual fast-acting buprenorphine

Also known as: Suboxone

Immediate-release sublingual buprenorphine/naloxone (SL-BPN/NX)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18 to 65 years old
• OAT indicated for moderate- to severe-OUD
• Attend a RAAM clinic in the North Simcoe Muskoka Local Health Integrated Network for opiate substitution treatment
• Successfully completed induction and stabilization OAT with Suboxone® tablet or film defined as receiving 8mg/2mg to 24mg/6mg of Suboxone® for ≥7 days with no evidence of allergic reaction to Suboxone®, Clinical Opiate Withdrawal Scale (COWS) score ≤12 (scale:0-48) for ≥24 hours, and Opiate Craving Visual Analog Scale (VAS) score ≤20 (scale:0-100)) for ≥24 hours
• Must have an active Ontario Health Insurance Plan number
• Must have a telephone that can receive calls, text messages or emails
• Must have drug insurance coverage for either medication for duration of study or demonstrate ability to pay for the drug out-of-pocket

You may not qualify if:

• Receiving any investigational drug for OUD in previous 4 weeks
• Congenital long QTc syndrome or QTc prolongation at baseline by electrocardiogram (QTc ≥450 milliseconds in men and QTc ≥470 milliseconds in women)
• Pregnant or lactating women
• Women of childbearing potential who are not using an effective and reliable method of contraception

Sponsors & Collaborators

• Royal Victoria Hospital, Canada: lead

Study Sites (5)

Royal Victoria Regional Health Centre

Barrie, Ontario, L4M6M2, Canada

Location

RAAM Clinic (Barrie)

Barrie, Ontario, L4N1K4, Canada

Location

RAAM Clinic (Midland0

Midland, Ontario, L4R0B7, Canada

Location

RAAM Clinic (Orillia)

Orillia, Ontario, L3V4S8, Canada

Location

RAAM Clinic (Wasaga Beach)

Wasaga Beach, Ontario, L9Z0C4, Canada

Location

Related Publications (32)

• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (5th ed.). (American Psychiatric Publishing, Inc., 2013).

  BACKGROUND

• Ontario Agency for Health Protection and Promotion. Opioid mortality surveillance report: analysis of opioid-related deaths in Ontario July 2017-June 2018. (2019).

  BACKGROUND

• Special Advisory Committee on the Epidemic of Opioid Overdoses. Opioid and Stimulant-related Harms in Canada. https://health-infobase.canada.ca/substance-related-harms/opioids-stimulants/ (2021).

  BACKGROUND

• Public Health Ontario. Opioid-related Morbidity and Mortality in Ontario. https://www.publichealthontario.ca/en/data-and-analysis/substance-use/interactive-opioid-tool#/trends (2021).

  BACKGROUND

• Nielsen S, Larance B, Degenhardt L, Gowing L, Kehler C, Lintzeris N. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database Syst Rev. 2016 May 9;(5):CD011117. doi: 10.1002/14651858.CD011117.pub2.

  PMID: 27157143 BACKGROUND

• Bruneau J, Ahamad K, Goyer ME, Poulin G, Selby P, Fischer B, Wild TC, Wood E; CIHR Canadian Research Initiative in Substance Misuse. Management of opioid use disorders: a national clinical practice guideline. CMAJ. 2018 Mar 5;190(9):E247-E257. doi: 10.1503/cmaj.170958. No abstract available.

  PMID: 29507156 BACKGROUND

• Sordo L, Barrio G, Bravo MJ, Indave BI, Degenhardt L, Wiessing L, Ferri M, Pastor-Barriuso R. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017 Apr 26;357:j1550. doi: 10.1136/bmj.j1550.

  PMID: 28446428 BACKGROUND

• Bahji A, Cheng B, Gray S, Stuart H. Reduction in mortality risk with opioid agonist therapy: a systematic review and meta-analysis. Acta Psychiatr Scand. 2019 Oct;140(4):313-339. doi: 10.1111/acps.13088.

  PMID: 31419306 BACKGROUND

• Galanter M, Femino J, Hunter B, Hauser M. Buprenorphine Treatment for Opioid Use Disorder in Community-Based Settings: Outcome Related to Intensity of Services and Urine Drug Test Results. Am J Addict. 2020 Jul;29(4):271-278. doi: 10.1111/ajad.13001. Epub 2020 Mar 11.

  PMID: 32162434 BACKGROUND

• Wiercigroch D, Sheikh H, Hulme J. A rapid access to addiction medicine clinic facilitates treatment of substance use disorder and reduces substance use. Subst Abuse Treat Prev Policy. 2020 Jan 13;15(1):4. doi: 10.1186/s13011-019-0250-1.

  PMID: 31931831 BACKGROUND

• Koehl JL, Zimmerman DE, Bridgeman PJ. Medications for management of opioid use disorder. Am J Health Syst Pharm. 2019 Jul 18;76(15):1097-1103. doi: 10.1093/ajhp/zxz105.

  PMID: 31361869 BACKGROUND

• Lofwall MR, Walsh SL, Nunes EV, Bailey GL, Sigmon SC, Kampman KM, Frost M, Tiberg F, Linden M, Sheldon B, Oosman S, Peterson S, Chen M, Kim S. Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial. JAMA Intern Med. 2018 Jun 1;178(6):764-773. doi: 10.1001/jamainternmed.2018.1052.

  PMID: 29799968 BACKGROUND

• Rosenthal RN, Ling W, Casadonte P, Vocci F, Bailey GL, Kampman K, Patkar A, Chavoustie S, Blasey C, Sigmon S, Beebe KL. Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone. Addiction. 2013 Dec;108(12):2141-9. doi: 10.1111/add.12315. Epub 2013 Sep 18.

  PMID: 23919595 BACKGROUND

• Rosenthal RN, Lofwall MR, Kim S, Chen M, Beebe KL, Vocci FJ; PRO-814 Study Group. Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial. JAMA. 2016 Jul 19;316(3):282-90. doi: 10.1001/jama.2016.9382.

  PMID: 27434441 BACKGROUND

• Ontario Drug Policy Research Network. Ontario Opioid Prescription Tool. https://odprn.ca/ontario-opioid-drug-observatory/ontario-prescription-opioid-tool/ (2018).

  BACKGROUND

• Pharmacoeconomic Review Report: Buprenorphine extended-release injection (Sublocade): (Indivior Canada, Ltd.): Indication: For the management of moderate-to-severe opioid use disorder in adult patients who have been inducted and clinically stabilized on a transmucosal buprenorphine-containing product [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Jul. Available from http://www.ncbi.nlm.nih.gov/books/NBK546358/

  PMID: 31532597 BACKGROUND

• Addictions & Mental Health Ontario. Ontario Provincial Standards for Withdrawal Management Services: 2021 Standards Manual. https://amho.ca/wp-content/uploads/AMHO-Final-WMS-Ontario-Provincial-Standards-for-Withdrawal-Management-Services-September-2021-AMHO-FINAL.pdf (2021)

  BACKGROUND

• Brens, C., Swoboda-Geen, C. & Gill, S. Simcoe Muskoka Opioid Strategy: An Action Plan for Our Communities. http://preventod.ca/Shared Documents/SMOS/SMOS Final Report - An Action Plan for Our Communities.pdf (2018)

  BACKGROUND

• Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003 Apr-Jun;35(2):253-9. doi: 10.1080/02791072.2003.10400007.

  PMID: 12924748 BACKGROUND

• McMillan DE, Gilmore-Thomas K. Stability of opioid craving over time as measured by visual analog scales. Drug Alcohol Depend. 1996 Mar;40(3):235-9. doi: 10.1016/0376-8716(96)01218-5.

  PMID: 8861402 BACKGROUND

• Fals-Stewart W, O'Farrell TJ, Freitas TT, McFarlin SK, Rutigliano P. The timeline followback reports of psychoactive substance use by drug-abusing patients: psychometric properties. J Consult Clin Psychol. 2000 Feb;68(1):134-44. doi: 10.1037//0022-006x.68.1.134.

  PMID: 10710848 BACKGROUND

• Reith FC, Van den Brande R, Synnot A, Gruen R, Maas AI. The reliability of the Glasgow Coma Scale: a systematic review. Intensive Care Med. 2016 Jan;42(1):3-15. doi: 10.1007/s00134-015-4124-3. Epub 2015 Nov 12.

  PMID: 26564211 BACKGROUND

• Institute for Clinical Evaluative Sciences. Data Dictionary. ICES Data Holdings Obligations for ICES Projects https://datadictionary.ices.on.ca/Applications/DataDictionary/Default.aspx?viewmode=DataAccess (2021)

  BACKGROUND

• Appropriate Use of Drug Testing in Clinical Addiction Medicine. J Addict Med. 2017 May/Jun;11 Suppl 3:1-56. doi: 10.1097/ADM.0000000000000322. No abstract available.

  PMID: 28557842 BACKGROUND

• Dennis BB, Sanger N, Bawor M, Naji L, Plater C, Worster A, Woo J, Bhalerao A, Baptist-Mohseni N, Hillmer A, Rice D, Corace K, Hutton B, Tugwell P, Thabane L, Samaan Z. A call for consensus in defining efficacy in clinical trials for opioid addiction: combined results from a systematic review and qualitative study in patients receiving pharmacological assisted therapy for opioid use disorder. Trials. 2020 Jan 6;21(1):30. doi: 10.1186/s13063-019-3995-y.

  PMID: 31907000 BACKGROUND

• Vernon MK, Revicki DA, Awad AG, Dirani R, Panish J, Canuso CM, Grinspan A, Mannix S, Kalali AH. Psychometric evaluation of the Medication Satisfaction Questionnaire (MSQ) to assess satisfaction with antipsychotic medication among schizophrenia patients. Schizophr Res. 2010 May;118(1-3):271-8. doi: 10.1016/j.schres.2010.01.021. Epub 2010 Feb 20.

  PMID: 20172695 BACKGROUND

• Ling W, Nadipelli VR, Solem CT, Ronquest NA, Yeh YC, Learned SM, Mehra V, Heidbreder C. Patient-centered Outcomes in Participants of a Buprenorphine Monthly Depot (BUP-XR) Double-blind, Placebo-controlled, Multicenter, Phase 3 Study. J Addict Med. 2019 Nov/Dec;13(6):442-449. doi: 10.1097/ADM.0000000000000517.

  PMID: 30844878 BACKGROUND

• World Health Organization. The World Health Organization Quality of Life (WHOQOL). WHOQOL BREF (2012)

  BACKGROUND

• Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, McLeod L, Delacqua G, Delacqua F, Kirby J, Duda SN; REDCap Consortium. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019 Jul;95:103208. doi: 10.1016/j.jbi.2019.103208. Epub 2019 May 9.

  PMID: 31078660 BACKGROUND

• Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30.

  PMID: 18929686 BACKGROUND

• Ministry of Health & Long-Term Care. Personal Health Information Protection Act. https://www.ontario.ca/laws/statute/04p03 (2004)

  BACKGROUND

• Dal-Re R, Avendano-Sola C, Bloechl-Daum B, de Boer A, Eriksson S, Fuhr U, Holm S, James SK, Mentz RJ, Perucca E, Rosendaal FR, Treweek S. Low risk pragmatic trials do not always require participants' informed consent. BMJ. 2019 Mar 27;364:l1092. doi: 10.1136/bmj.l1092. No abstract available.

  PMID: 30917969 BACKGROUND

MeSH Terms

Interventions

Sublocade; Buprenorphine, Naloxone Drug Combination

Intervention Hierarchy (Ancestors)

Buprenorphine; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Philip Wong, MN

  Royal Victoria Regional Health Centre

  PRINCIPAL INVESTIGATOR

• Giulio DiDiodato, PhD

  Royal Victoria Regional Health Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelly Cruise, BHSc

CONTACT

7057289090; cruisek@rvh.on.ca

Christine DiMarco

CONTACT

7057289090; dimarcoc@rvh.on.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Assessor blinded to intervention code.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Research Scientist

Model Details: Pragmatic, multi-centre, randomised, controlled, open-label, superiority study with two parallel groups and primary endpoints of opioid positivity and healthcare utilization at 12 months after enrollment. Randomization will be performed with a 1:1 allocation ratio using a stratified, permuted-block group schema according to the following strata (no fixed ratio): 1. RAAM clinic site (Barrie, Orillia, Midland, Wasaga Beach) 2. Severity of OUD according to DSM-V criteria (moderate vs severe)

Study Record Dates

• First Submitted: October 17, 2022
• First Posted: October 26, 2022
• Study Start: December 1, 2022
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: October 26, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5)