Long Acting Buprenorphine Injection Compared to Sublingual Buprenorphine/Naloxone Films

NCT03744663 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: IRB00054516
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

While substance use disorders have been found to have relapse rates on part with other chronic illnesses such as hypertension and asthma long term abstinence remains elusive for many. The FDA has recently approve a long acting subcutaneous injectable formulation of buprenorphine. This study aims to determine the feasibility of enrolling and randomizing patients seeking treatment at an outpatient substance abuse clinic to buprenorphine/naloxone films which dissolve under the tongue vs. long acting buprenorphine injection with all other treatment aspects held constant. The study also aims to determine the effectiveness of monthly injections of Sublocade® compared to daily oral Suboxone® SL therapy in the treatment of moderate to severe opioid use disorder after twenty-four weeks of treatment.

Conditions

Opioid Use

Keywords

opioid; Opioid Agonist Treatment; buprenorphine; substance abuse; drug; abstinence

Outcome Measures

Primary Outcomes (11)

• Number of Weeks patients continued in treatment during trial period

  Retention in weeks

  26 weeks

• Number of Participants that Dropout during the first 28 days of Treatment

  Number of participants that leave the study

  first 28 days

• Number of participants that complete of the treatment phase

  Number of participants that complete the study

  26 weeks

• Number of participants who did not complete the trial in their assigned group

  Total number of participants that changed arms

  26 weeks

• Percentage of negative urinary drug screens

  percentage of participants that have a negative drug screen

  26 weeks

• Liver enzyme values - ALP, AST, ALT

  Values of liver enzymes will be measured: Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT). Values will be reported in IU/L

  26 weeks

• Liver enzyme values- Total Bilirubin

  Values of liver enzymes will be measured: Total Bilirubin. Values will be reported in mg/dL

  26 weeks

• Clinical Opiate Withdrawal Scale (COWS) scores trends

  Withdrawal symptoms scale- total score 0-48 with a lower score denoting no symptoms (better Outcomes) and higher score denoting more withdrawal symptoms

  26 weeks

• Subjective Opiate Withdrawal Scale (SOWS) score trends

  Participant survey for how they are feeling during withdrawal period, score range from 0 to 64. Low score denotes no/less perceived symptoms (better outcomes) and higher score denotes high/ more personal perceived symptoms.

  26 weeks

• Number or patients still in medication assisted therapy (MAT) clinic 6 months after trial period ends.

  Number of patients still in MAT clinics at 6 months

  6 months

• Number of participants death

  Number of Participants deaths 6 months after initial participant consent is given.as measured by Vital Statistics database

  6 months

Study Arms (2)

Suboxone® SL

ACTIVE COMPARATOR

Patients assigned to this group will continue with their already established dose of Suboxone ® SL films for 24 weeks along with weekly therapy.

Drug: Suboxone® SL

Sublocade®

EXPERIMENTAL

Patients assigned to the Sublocade® group will receive the study drug (300 mg subcutaneously) every 4 weeks for a total of 6 doses along with weekly therapy.

Drug: Sublocade®

Interventions

Suboxone® SL DRUG

Subjects will be started and titrated to optimal Suboxone® SL dose for 14 days. After the 14 day induction phase, the subject will be started on the treatment to which they were randomized to two groups one of which will be Suboxone® SL.

Also known as: Suboxone® SL films, buprenorphine naloxone

Suboxone® SL

Sublocade® DRUG

Subjects will be started and titrated to optimal Suboxone® SL dose for 14 days. After the 14 day induction phase, the subject will be started on the treatment to which they were randomized, either Suboxone® SL or Sublocade®. Subjects with significant opioid craving (\> 20 mm on the Opioid Craving Visual Analog Scale) or withdrawal (a score of \> 12 on the Clinical Opiate Withdrawal Scale) after 14 days of treatment will be started on Sublocade® only at the consensus of the research team. Otherwise they will undergo an additional 7 day titration period. Study drug with Sublocade® group: Patients assigned to this group will receive the study drug (300 mg subcutaneously) every 4 weeks for a total of 6 doses along with weekly therapy. The location and specifications of its application will follow the recommendations by the FDA previously published.

Also known as: buprenorphine extended-release

Sublocade®

Eligibility Criteria

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

You may qualify if:

• Subjects who present to the WFBMC Medication-Assisted-Therapy (MAT) clinic seeking OBOT.

You may not qualify if:

• Those patients who have:
• history of cirrhosis, \>= CKD stage 3
• congenital long QT syndrome
• those on antiarrhythmic medications
• liver enzymes more than 2 times the upper normal value at baseline assessment
• elevated bilirubin
• chronic pulmonary condition
• current unstable and untreated psychiatry comorbid disorder
• pregnant
• use of benzodiazepines/other CNS depressant medications

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Related Publications (20)

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• Prevention CfDCa. Heroin Overdose Data. US Department of Health and Human Services. https://www.cdc.gov/drugoverdose/data/heroin.html. Published Jan 2017. Updated 2018-08-31T12:47:34Z. Accessed September 3 2018.

  BACKGROUND

• Rudd RA, Seth P, David F, Scholl L. Increases in Drug and Opioid-Involved Overdose Deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016 Dec 30;65(50-51):1445-1452. doi: 10.15585/mmwr.mm655051e1.

  PMID: 28033313 BACKGROUND

• Fleischauer AT, Ruhl L, Rhea S, Barnes E. Hospitalizations for Endocarditis and Associated Health Care Costs Among Persons with Diagnosed Drug Dependence - North Carolina, 2010-2015. MMWR Morb Mortal Wkly Rep. 2017 Jun 9;66(22):569-573. doi: 10.15585/mmwr.mm6622a1.

  PMID: 28594786 BACKGROUND

• Zibbell JE, Iqbal K, Patel RC, Suryaprasad A, Sanders KJ, Moore-Moravian L, Serrecchia J, Blankenship S, Ward JW, Holtzman D; Centers for Disease Control and Prevention (CDC). Increases in hepatitis C virus infection related to injection drug use among persons aged </=30 years - Kentucky, Tennessee, Virginia, and West Virginia, 2006-2012. MMWR Morb Mortal Wkly Rep. 2015 May 8;64(17):453-8.

  PMID: 25950251 BACKGROUND

• Peters PJ, Pontones P, Hoover KW, Patel MR, Galang RR, Shields J, Blosser SJ, Spiller MW, Combs B, Switzer WM, Conrad C, Gentry J, Khudyakov Y, Waterhouse D, Owen SM, Chapman E, Roseberry JC, McCants V, Weidle PJ, Broz D, Samandari T, Mermin J, Walthall J, Brooks JT, Duwve JM; Indiana HIV Outbreak Investigation Team. HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014-2015. N Engl J Med. 2016 Jul 21;375(3):229-39. doi: 10.1056/NEJMoa1515195.

  PMID: 27468059 BACKGROUND

• Drug Enforcement Administration, Department of Justice.. Implementation of the Provision of the Comprehensive Addiction and Recovery Act of 2016 Relating to the Dispensing of Narcotic Drugs for Opioid Use Disorder. Final rule. Fed Regist. 2018 Jan 23;83(15):3071-5.

  PMID: 29359892 BACKGROUND

• Public policy statement on Office-Based Opioid Agonist Treatment (OBOT). J Addict Dis. 2005;24(3):153-61. doi: 10.1300/J069v24n03_12. No abstract available.

  PMID: 16186090 BACKGROUND

• Hser YI, Saxon AJ, Huang D, Hasson A, Thomas C, Hillhouse M, Jacobs P, Teruya C, McLaughlin P, Wiest K, Cohen A, Ling W. Treatment retention among patients randomized to buprenorphine/naloxone compared to methadone in a multi-site trial. Addiction. 2014 Jan;109(1):79-87. doi: 10.1111/add.12333. Epub 2013 Oct 9.

  PMID: 23961726 BACKGROUND

• Kakko J, Svanborg KD, Kreek MJ, Heilig M. 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. Lancet. 2003 Feb 22;361(9358):662-8. doi: 10.1016/S0140-6736(03)12600-1.

  PMID: 12606177 BACKGROUND

• Yokell MA, Zaller ND, Green TC, Rich JD. Buprenorphine and buprenorphine/naloxone diversion, misuse, and illicit use: an international review. Curr Drug Abuse Rev. 2011 Mar;4(1):28-41. doi: 10.2174/1874473711104010028.

  PMID: 21466501 BACKGROUND

• Winchell C. Cross-Discipline Team Leader Review and Summary Basis for Approval. In: Administration FD, ed: Federal Drug Administration; 2017.

  BACKGROUND

• (2017) USFDA. Press Announcements - FDA approves first once-monthly buprenorphine injection, a medication-assisted treatment option for opioid use disorder. 2018.

  BACKGROUND

• Johnson RE, Chutuape MA, Strain EC, Walsh SL, Stitzer ML, Bigelow GE. A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med. 2000 Nov 2;343(18):1290-7. doi: 10.1056/NEJM200011023431802.

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• Surgeon General's Report: Facing Addiction in America. In: Services USDoHaH, ed. 200 Independence Avenue SW Washington DC 20201: U.S. Department of Health and Human Services; 2017.

  BACKGROUND

• Park-Lee E, Lipari RN, Hedden SL, Kroutil LA, Porter JD. Receipt of Services for Substance Use and Mental Health Issues Among Adults: Results from the 2016 National Survey on Drug Use and Health. 2017 Sep. In: CBHSQ Data Review. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK481724/

  PMID: 29431966 BACKGROUND

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  PMID: 25583888 BACKGROUND

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

Buprenorphine, Naloxone Drug Combination; Sublocade

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

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

• Erin Barnes, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients admitted to the WFBMC Medication-Assisted-Therapy (MAT) clinic with a diagnosis of moderate/severe Opioid-Use Disorders (OUD) who are more than 18 years old will be approached for enrollment in this study. Because of the nature of a pilot study, it's proposed a total of 30 patients, 15 in each group. Subjects will be started and titrated to optimal Suboxone® SL dose for 14 days. After the 14 day, the subject will be started on the treatment to which they are randomized, either Suboxone® SL or Sublocade®. Control group -Suboxone®SL: Patients assigned to this group will continue with their already established dose of Suboxone ®SL films for 24 weeks along with weekly therapy. Study drug-Sublocade® group: Patients assigned to this group will receive the study drug (subcutaneously) every 4 weeks for a total of 6 doses along with weekly therapy. At the end of the 24-weeks subjects will continue the medication of their choice within the constraints of their insurance provider.

Study Record Dates

• First Submitted: November 9, 2018
• First Posted: November 16, 2018
• Study Start: June 1, 2022
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: June 6, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share