Long Acting Buprenorphine Injection Compared to Sublingual Buprenorphine/Naloxone Films

Opioid Use Clinical Trial

Official title:

A Randomized Pilot Study of Long Acting Buprenorphine Injection Compared to Sublingual Buprenorphine/Naloxone Films

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03744663
• Other study ID #: IRB00054516
• Status: Withdrawn
• Phase: Phase 2
• Start date: June 2022
• Est. completion date: December 2022

Study information

• Verified date: June 2022
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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. Fortunately, the FDA has recently approved a long acting subcutaneous injectable formulation of buprenorphine. While this drug has proven effective in retaining patients in care and decreasing drug cravings as compared to placebo, this drug has not been tested in a real world clinic setting and no studies exist comparing it to the current formulations of buprenorphine. The objective of this study is to perform a randomized pilot study directly comparing sublingual buprenorphine/naloxone to long acting buprenorphine subdermal injection in a standard Office-Based Opioid Agonist Treatment (OBOT) clinic. The study team will compare patient retention, percentage of negative urinary drug screens, and withdrawal scores between the two groups. The findings will provide insight for US providers seeking more effective and efficient ways to treat Opioid use disorder (OUD) in the outpatient setting.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Opioid Use

Intervention

Drug:
• Suboxone® SL
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.
• Sublocade®
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

References & Publications (20)

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Jones CM, Campopiano M, Baldwin G, McCance-Katz E. National and State Treatment Need and Capacity for Opioid Agonist Medication-Assisted Treatment. Am J Public Health. 2015 Aug;105(8):e55-63. doi: 10.2105/AJPH.2015.302664. Epub 2015 Jun 11. — View Citation

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. — View Citation

Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014 Feb 6;(2):CD002207. doi: 10.1002/14651858.CD002207.pub4. Review. — View Citation

McLellan AT, Lewis DC, O'Brien CP, Kleber HD. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA. 2000 Oct 4;284(13):1689-95. Review. — View Citation

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. In: CBHSQ Data Review. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); September 2017:1-35.

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. — View Citation

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.

Public policy statement on Office-Based Opioid Agonist Treatment (OBOT). J Addict Dis. 2005;24(3):153-61. — View Citation

Rosenblatt RA, Andrilla CH, Catlin M, Larson EH. Geographic and specialty distribution of US physicians trained to treat opioid use disorder. Ann Fam Med. 2015 Jan-Feb;13(1):23-6. doi: 10.1370/afm.1735. — View Citation

Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Increases in Drug and Opioid Overdose Deaths--United States, 2000-2014. MMWR Morb Mortal Wkly Rep. 2016 Jan 1;64(50-51):1378-82. doi: 10.15585/mmwr.mm6450a3. — View Citation

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. — View Citation

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.

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

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. Review. — View Citation

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. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Weeks patients continued in treatment during trial period	Retention in weeks	26 weeks
Primary	Number of Participants that Dropout during the first 28 days of Treatment	Number of participants that leave the study	first 28 days
Primary	Number of participants that complete of the treatment phase	Number of participants that complete the study	26 weeks
Primary	Number of participants who did not complete the trial in their assigned group	Total number of participants that changed arms	26 weeks
Primary	Percentage of negative urinary drug screens	percentage of participants that have a negative drug screen	26 weeks
Primary	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
Primary	Liver enzyme values- Total Bilirubin	Values of liver enzymes will be measured: Total Bilirubin. Values will be reported in mg/dL	26 weeks
Primary	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
Primary	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
Primary	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
Primary	Number of participants death	Number of Participants deaths 6 months after initial participant consent is given.as measured by Vital Statistics database	6 months