Long Acting Buprenorphine Injection Compared to Sublingual Buprenorphine/Naloxone Films

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Opioid Use

Intervention / Treatment
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* Drug: Suboxone® SL
* Drug: Sublocade®


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Suboxone® SL<br>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<br>* 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.<br>* Other names: buprenorphine naloxone;|
| Experimental: Sublocade®<br>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®<br>* 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.<br>* Other names: buprenorphine extended-release;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid, Opioid Agonist Treatment, buprenorphine, substance abuse, drug, abstinence