Clinical trial NCT03604159
Conditions: Opioid Dependence
Keywords: Opioid dependence Buprenorphine primary care treatment extended-release buprenorphine
Sponsor: NYU Langone Health
Start date: 2019-06-24; Completion date: 2020-05-04
Enrollment: 52 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a pilot proof-of-concept randomized controlled trial, open-label and unblinded, examining the feasibility and acceptability of Buprenorphine extended-release vs. daily sublingual buprenorphine-naloxone for the treatment of opioid use disorder in jail and at community re-entry.

Detailed description:

Arms: arm 1: XRB is a 300mg pre-mixed subcutaneous injectable formulation to be administered monthly. XRB is for abdominal subcutaneous injection only. Participants in the XRB treatment arm will be given 1 or more XRB injections prior to release from jail and one more at week 5 post-release, depending on their release date. arm 2: SLB (SUBOXONE, Zubsolv, or generic tablets) is a daily sublingual film or tablet ranging from 8-24mg/day or equivalent (Zubsolv is dosed 5.7-17.1 mg/day). The film or tablet is placed under the tongue for 5 to 10 minutes until dissolved completely. Participants in the SLB treatment arm will be provided SLB daily by observed dosing in-jail (controlled substances are not self-administered in-jail) and and encouraged to continue SLB treatment in weekly, bi-weekly, or monthly quantities for unobserved, daily, self-administration through week 5. Patients may also elect to obtain SLB care free-of-charge from the Bellevue Hospital Center Addiction Medicine clinic or from non-NYU/Bellevue providers and pharmacies per usual care standards. SLB will not be provided via the study.
Interventions: intervention 1: Buprenorphine Extended Release intervention 2: Sublingual Buprenorphine (SUBOXONE, Zubsolv, or generic tablets)
Intervention descriptions: intervention 1: XRB is available in dosage strengths of 100 mg/0.5 mL and 300 mg/1.5 mL buprenorphine. Each dose is provided in a prefilled syringe with a 19 gauge 5/8-inch needle. intervention 2: SLB is administered sublingually or buccally as a single daily dose. Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not advised in early treatment or without appropriate follow-up visits. After treatment induction and stabilization, the maintenance dose of SLB is generally in the range of 4mg/1mg buprenorphine/naloxone to 24mg/6mg buprenorphine/naloxone per day depending on the individual patient and clinical response.

Protocol documents:
Prot_SAP_000.pdf: 
CLINICAL STUDY PROTOCOL 
 
 
 
 
Buprenorphine extended-release in jail 
and at re-entry: pilot proof-of-concept 
open-label randomized controlled trial 
vs. daily sublingual buprenorphine-
naloxone 
Clinical Phase 
Phase IV 
 
 
Sponsor 
National Institute on Drug Abuse 
Protocol Version 
December 11, 2019 
version 10 
 
 
 
Study Number: 18-00823 
NCT: NCT03604159 
 
Confidentiality Statement: 
This study will be conducted in accordance with the Code of Federal Regulations on the 
Protection of Human Subjects (45 CFR Part 46), any other applicable US government 
research regulations, and institutional research policies and procedures. The Principal 
Investigator will assure that no deviation from, or changes to the protocol will take place 
without prior agreement from the sponsor and documented approval from the Institutional 
Review Board (IRB), except where necessary to eliminate an immediate hazard(s) to the 
trial participants. All personnel involved in the conduct of this study have completed Human 
Subjects Protection Training. 


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Study Personnel 
Principal Investigator 
Joshua D Lee 
New York University 
Email: Joshua.Lee@nyulangone.org 
 
 
Co-Investigators 
Jonathan Giftos, MD 
NYC Health+Hospitals 
Email: giftosj@nychhc.org 
 
Ross MacDonald, MD 
NYC Health+Hospitals 
Email: rmacdonald@nychhc.org 
 
Key Study Personnel: 
Ryan Mcdonald 
New York University 
Email: Ryan.Mcdonald@nyulangone.org 
 
Monica Malone 
New York University 
Email: Mia.Malone@nyulangone.org 
 
Nadina Santana-Correa 
New York University 
Email: Nadina.Santana-Correa@nyulangone.org 
Wanda Bonilla 
New York University 
Email: Wanda.Bonilla@nyulangone.org 
 
 


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Synopsis 
 
Primary Objective 
Feasibility and Implementation: Estimate the feasibility and ease of use of XRB vs. SLB 
as measured by initial patient preference and acceptability, in-treatment patient 
satisfaction, patient qualitative interviews, jail visit frequency and program cost 
estimates, and rates of medication diversion. 
Secondary Objectives 
Treatment Retention: Estimate the effectiveness of XRB vs. SLB in improving rates of 
community treatment initiation/continuation post-release. 
Clinical Effectiveness: Estimate the effectiveness of XRB vs. SLB in decreasing illicit 
opioid (e.g. heroin) use post-release. 
Naturalistic Comparative Effectiveness: Evaluate outcomes of XRB vs. SLB in the context 
of the XRNTX, ETAU, and Methadone outcomes accrued in the larger SOMATICS-XOR 
RCT. 
Primary Outcome Variables 
1. Initial patient preference and acceptability measured via baseline, initial patient 
interviews 
2. In-treatment patient satisfaction measured using follow-up surveys, qualitative 
interviewing, and clinical research forms 
3. Jail visit frequency and program cost estimates 
4. Rates of medication diversion. 
Secondary and Exploratory Outcome Variables 
1. XRB vs. SLB in improving rates of community treatment initiation/continuation post- 
release. 
2. Estimate the effectiveness of XRB vs. SLB in decreasing illicit opioid (e.g. heroin) use 
post-release. 
3. Evaluate outcomes of XRB vs. SLB in the context of the XRNTX, ETAU, and 
Methadone outcomes accrued in the larger SOMATICS-XOR RCT 
Study Duration 
June 28, 2019 — June 27, 2020 


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Study Design 
This Administrative Supplement proposal takes advantage of the existing SOMATICS- 
XOR U01 (NIDA) trial design and infrastructure to conduct a new pilot, N=50, proof-of- 
concept, open-label, non-blinded randomized controlled trial of XRB vs. SLB. 
Study Population 
Adult jail inmates with upcoming release date, current opioid dependence and currently 
maintained on sublingual buprenorphine-naloxone. N=50. 
Number of Participants 
N=50 


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Study Flowchart 
 
Prior to  
Enrollment 
Visit 0 
Screening 
 
 
Visit 0 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   Visit 1-4 
Follow-Up 
Treatment 
 
 
Visit 5 
Final Study 
Visit 
     
 
 
 
 
    Visit 6-10 
Extension 
Study 
Treatment 
Visits 
 
 
    Visit 11 
Extension 
Study Final 
Visit Total
 N: 50 Obtain informed consent 
and HIPAA Authorization.
 Screen
 potential subjects
 by 
inclusion and 
exclusion criteria;
 obtain
 medical history,
 document informed consent and confirmation
of 
eligibility in source
 records.
 Follow-Up
 Treatment Visits 
Administrative data
for SLB medication refills and post-release XRB injections, Timeline Followback,
 Urine
 specimen collection &  testing, adverse event and serious adverse even reporting,
 NYS prescription
 monitoring data for community
 SLB refill reporting, open 
ended-interview, treatment
 retention.
 At
 Visit
 3,
 week
 4  second
 XRB
 administered
 
Perform Baseline Assessments ASILite, 
Timeline Followback,
 Demographics,
 MOUD Preference Form, Electronic
 Medical Records
 medical and psychiatric
 history
 Randomization
 
Buprenorphine 
Extended-Release 
Sublingual 
Buprenorphine 
Final Study Visit 
Medication is not dispensed. Timeline Followback, treatment retention, Urine specimen collection 
& testing, adverse event and serious adverse event reporting, NYS prescription monitoring data 
for community SLB refill reporting, open- ended interviews with participants concerning XRB vs. 
SLB treatment satisfaction and ease-of-use 
XRB Extension Treatment Visits 
Administrative data for initial and/or additional XRB injections, Timeline Followback, Urine specimen 
collection & testing, adverse event and serious adverse even reporting. At Visit 7 and 10, pregnancy 
test, qualitative interviews for eligible XRB participants 
XRB Extension Final Safety Visit 
Adverse event and serious adverse even reporting. Timeline Followback, Treatment Satisfaction, 
Qualitative Interviews if applicable. 


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Table of Contents 
1 - Introduction ........................................................................................................................ 9 
1.1 Introductory Statement .................................................................................................. 9 
2 - Background ...................................................................................................................... 10 
2.1.1 Preclinical Experience ........................................................................................... 10 
2.1.2 Clinical Experience ................................................................................................ 10 
2.2 Background/prevalence of research topic .................................................................... 10 
3 - Rationale/Significance ..................................................................................................... 11 
3.1 Problem Statement ...................................................................................................... 11 
3.2 Purpose of Study/Potential Impact .............................................................................. 11 
3.3.1 Potential Benefits................................................................................................... 13 
3.3.2 Potential Risks ....................................................................................................... 14 
4 - Study Objectives ................................................................................................................ 15 
4.1 Hypothesis ................................................................................................................... 15 
4.2 Primary Objective......................................................................................................... 15 
4.3 Secondary Objectives .................................................................................................. 15 
5 - Study Design .................................................................................................................... 16 
5.1 General Design ............................................................................................................ 16 
5.1.1 Study Duration ....................................................................................................... 16 
5.1.2 Number of Study Sites .......................................................................................... 16 
5.2.1 Primary Outcome Variables .................................................................................. 16 
5.2.2 Secondary and Exploratory Outcome Variables ................................................... 17 
5.3 Study Population .......................................................................................................... 17 
5.3.1 Number of Participants .......................................................................................... 17 
5.3.2 Eligibility Criteria/Vulnerable Populations ............................................................. 17 
6 - Methods ............................................................................................................................. 19 
6.1.1 Identity of Investigational Product/New Drug ........................................................ 19 
6.1.2 Dosage, Admin, Schedule ..................................................................................... 19 
6.1.3 Method of Assignment/Randomization ................................................................. 19 
6.1.4 Blinding and Procedures for Unblinding ............................................................... 19 
6.1.5 Packaging/Labelling .............................................................................................. 20 


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6.1.6 Storage Conditions ................................................................................................ 20 
6.1.7 Concomitant therapy ............................................................................................. 20 
6.1.8 Restrictions ............................................................................................................ 20 
6.2 Assessments ................................................................................................................ 21 
6.2.1 Efficacy .................................................................................................................. 21 
6.2.2 Safety/Pregnancy-related policy ........................................................................... 21 
6.2.2.1 Adverse Events Definition and Reporting ............................................................ 21 
6.2.3 Pharmacokinetics .................................................................................................. 23 
6.2.4 Biomarkers............................................................................................................. 23 
6.3 Study Procedures .......................................................................................................... 23 
6.3.1 Study Schedule ..................................................................................................... 23 
6.3.2 Informed Consent .................................................................................................. 27 
6.3.3 Screening............................................................................................................... 27 
6.3.4 Recruitment, Enrollment and Retention ................................................................ 27 
6.3.5 On Study Visits ...................................................................................................... 28 
6.3.6 End of Study and Follow-up .................................................................................. 30 
6.3.7 Removal of subjects .............................................................................................. 30 
6.4.1 Statistical Design ................................................................................................... 30 
6.4.2 Sample Size Considerations ................................................................................. 31 
6.4.3 Handling of Missing Data ...................................................................................... 31 
7 - Trial Administration ............................................................................................................ 32 
7.1 Ethical Considerations ................................................................................................... 32 
7.2 Institutional Review Board (IRB) Review .................................................................... 32 
7.3 Subject Confidentiality ................................................................................................. 32 
7.4 Deviations/Unanticipated Problems ............................................................................ 33 
7.5 Data Quality Assurance ............................................................................................... 34 
7.5.1 Data Collection ...................................................................................................... 34 
7.5.1.1 Access to Source ............................................................................................... 34 
7.5.1.2 Data Storage/Security ........................................................................................ 36 
7.6 Study Records ............................................................................................................. 36 
7.6.1 Retention of Records ............................................................................................. 36 
7.7 Study Monitoring .......................................................................................................... 37 


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7.8 Data Safety Monitoring Plan ........................................................................................ 37 
7.9 Study Modification........................................................................................................ 37 
7.10 Study Discontinuation ................................................................................................ 37 
7.11 Study Completion ...................................................................................................... 38 
7.12 Conflict of Interest Policy ........................................................................................... 38 
7.13 Funding Source ......................................................................................................... 38 
Appendices ............................................................................................................................. 39 
List of Tables ........................................................................................................................... 40 
References .............................................................................................................................. 41 


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1 - Introduction 
1.1 Introductory Statement 
This is a pilot proof-of-concept randomized controlled trial, open-label and unblinded, 
examining the feasibility and acceptability of Buprenorphine extended-release vs. daily 
sublingual buprenorphine-naloxone for the treatment of opioid use disorder in jail and at 
community re-entry. 


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2 - Background 
2.1.1 Preclinical Experience 
Buprenorphine, a partial μ-opioid receptor agonist, was approved by the Food and Drug 
Administration in 2002 as office-based pharmacotherapy for opioid dependence. As an 
opioid partial agonist, buprenorphine can produce some opioid-like effects such as euphoria 
or respiratory depression, however, its maximal effects are less than those of full agonists 
like heroin and methadone. At low doses Buprenorphine produces sufficient agonist effect to 
enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing 
withdrawal symptoms. Buprenorphine's opioid effects increase with each dose until at 
moderate doses they level off, even with further dose increases. This "ceiling effect" lowers 
the risk of misuse, dependency, and side effects (1). 
2.1.2 Clinical Experience 
Monthly, injectable, buprenorphine extended-release (XRB, SublocadeTM, Indivior) is the 
most recently approved pharmacotherapy for opioid use disorders in the U.S.(2). XRB is 
available as of March-2018 in a pre-mixed subcutaneous formulation, administered monthly, 
and equivalent to a 16-24mg/day maintenance dose of sublingual buprenorphine-naloxone 
(SLB). In this pilot proposal, Buprenorphine extended-release (XRB) or sublingual 
buprenorphine (SLB) daily maintenance will be provided per usual Opioid Treatment 
Program protocols in-jail and prior to release. Both medications will be available through the 
study and the Bellevue Hospital Addiction Medicine clinic free-of-charge. XRB consists of a 
once monthly abdominal subcutaneous injection using a pre-filled syringe, per usual 
package insert instructions. SLB is a delivered daily by observed dosing in-jail (controlled 
substances are not self-administered in-jail). Post-release, all participants may elect to 
continue SLB maintenance with the Bellevue Primary Care Addiction Medicine clinic, or may 
pursue SLB maintenance from non-NYU/Bellevue community providers. SLB is available 
free of charge to uninsured patients at Bellevue Hospital Center, or participants may fill SLB 
prescriptions at community pharmacies. SLB medication will not be provided by the study 
itself. 
2.2 Background/prevalence of research topic 
In 2016, opioids were involved in 42,249 deaths and opioid overdose deaths were five times 
higher than in 1999 (3). On average, 115 Americans die every day from an opioid overdose 
(4). The opioid and overdose epidemic has intensified efforts to expand and optimize 
effective medication treatment for opioid use disorder (methadone, extended-release 
naltrexone, buprenorphine) in criminal justice and primary care populations. Despite the 
effectiveness of methadone and buprenorphine maintenance as standard of care in NYC 
jails, only about 30% of individuals initiating buprenorphine maintenance in-jail successfully 
link to community treatment post-release. XRB is newly FDA approved and its effectiveness 
in a criminal justice setting is promising but untested. 


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3 - Rationale/Significance 
3.1 Problem Statement 
The opioid epidemic in the United States continues to worsen. New York City currently has a 
robust methadone and buprenorphine maintenance program for adults with opioid use 
disorder (OUD). However, despite these standards-of-care, outcomes for all OUD patients, 
including buprenorphine patients, in NYC following release from jail are in need of 
improvement. Overdose rates in NYC continue to worsen, including among recently 
incarcerated individuals (5). Only about 30% of individuals initiating buprenorphine 
maintenance for opioid use disorders (OUDs) in-jail currently successfully link to community 
treatment post-release (6), which has been a finding in a previous NIDA clinical trial and 
observational studies we have conducted at NYU-Bellevue (7, 8). 
3.2 Purpose of Study/Potential Impact 
Monthly, injectable, buprenorphine extended-release (XRB, SublocadeTM, Indivior) is the 
most recently approved pharmacotherapy for opioid use disorders in the US. XRB is 
available as of March-2018 in a pre-mixed subcutaneous formulation, administered monthly, 
and equivalent to a 16-24mg/day maintenance dose of sublingual buprenorphine-naloxone 
(SLB). 
XRB offers several advantages to other forms of 'medication treatment for opioid use 
disorders’ (MOUD), which currently consist of daily sublingual buprenorphine (Suboxone 
films, Zubsolv, or generic buprenorphine-naloxone tablets), daily oral methadone 
maintenance delivered in Opioid Treatment Programs, or extended-release naltrexone (XR- 
NTX). None of these earlier medications have proven to be 'killer apps', and uptake of 
MOUD in US correctional facilities (jails, prisons) and community-supervised populations 
(drug courts, parole programs) lag the public health need and high overdose risk in these 
settings and populations. Buprenorphine products in particular have been relatively 
shunned in CJS, likely due to staffing constraints required by observed induction and daily 
dosing, concerns regarding diversion and misuse, and common stigmas related to opioid 
agonist (methadone or buprenorphine) maintenance approaches (9). 
NYC jails are an exception to this sub-par US CJS standard, in part due to the current 
leadership of this proposal's Co-Investigators at NYC Health+Hospitals Correctional Health 
Services, Ross MacDonald MD and Jonathan Giftos MD, who are, respectively, Chief 
Medical Officer and Clinical Director of Substance Use Treatment/Medical Director of the 
Opioid Treatment Program for all of NYC jails. NYC has a robust methadone and 
buprenorphine maintenance program for adults with OUD. Despite these standards-of-care, 
outcomes for all OUD patients, including buprenorphine patients, in NYC following release 
from jail are in need of improvement. Overdose rates in NYC continue to worsen, including 
among recently incarcerated individuals (5). Only about 30% of individuals initiating 
buprenorphine maintenance for opioid use disorders (OUDs) in-jail currently successfully 
link to community treatment post-release (6) which has been a finding in a previous NIDA 
clinical trial and observational studies we have conducted at NYU-Bellevue (7, 8) . Major 
obstacles to office-based opioid treatment (OBOT) with  MOUD following re-entry include 
limited mobility and communication due to incarceration, administrative support for bridging 


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to a new clinic, high risks of drug/alcohol relapse, and rigid, impersonal treatment 'systems' 
which are often not customized to or welcoming of the recently incarcerated. 
The new buprenorphine extended-release formulation (XRB) has several potential feasibility 
and effectiveness advantages vs. daily sublingual buprenorphine (SLB), including: 1) fewer 
overall medical, nursing, and pharmacy visits, fewer correctional staff hours, and potentially 
lower program costs vs. daily observed dosing, 2) near zero probability of diversion/misuse 
vs. frequent diversion, 3) an improved, long-acting 'bridge' of medication adherence at 
release, which is crucial as patients struggle to continue daily SLB adherence, avoid 
relapse, and connect to community treatment. The current NYC jail high-volume 
buprenorphine maintenance program provides an ideal setting in which to pilot XRB vs. 
SLB. 
Rikers Island and the New York City Department of Corrections administered jail system in 
NYC is a prominent exception to US norms. NYC Health+Hospitals Division of Correctional 
Health Services, which administers all jail-based health care in NYC,  and has a high- 
volume program for both continuing existing SLB patients through incarceration and 
initiating SLB in new patients prior to release. NYC jails provide an ideal setting in which to 
pilot jail-based use of newer extended-release buprenorphine compounds. Two members of 
NYC Health+Hospitals leadership, are key co-investigators in this proposal. This pilot will be 
a first of its kind evaluation of XRB in a criminal justice, underserved population at high risk 
or relapse and overdose. 
3.3.1 Potential Benefits 
This proposal will likely be the first or among the first high-quality RCT evaluations of XRB in 
a criminal justice setting. Both XRB and SLB standard of care are safe, efficacious 
medications for the treatment of OUDs. The expected benefits in the XRB group are fewer 
medication and nursing visits during incarceration, continuous long-acting medication 
treatment at release and prior to the first community treatment visit, and potentially a lower 
risk of relapse to heroin and other drug/alcohol use vs. SLB.  In addition the XRB is 
delivered free of charge. The SLB treatment-as-usual group will receive the same 
compensation and encouragement to continue care both in custody and following release, 
which will be above and beyond usual care.  Both arms, however, may experience no 
benefit from study participation, if the medications are not effective, acceptable, or if post- 
release follow-up is not pursued or completed. The extra XRB medical treatment, pre- and 
post-release counseling (both arms), and monetary compensation (both arms) is intended 
and unlikely to be coercive – that is, motivate persons to participate in the trial against their 
preferences or wishes. These benefits are on par with other recent and approved NYC jail 
opioid treatment trials which attempt to provide adequate but non-coercive benefits to all 
participants. The XRB medication free of charge or the modest monetary compensation is 
unlikely to sway an individual with other good options including jail-based methadone and 
buprenorphine treatment and no other interest in participating in or following up during the 
trial. 


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3.3.2 Potential Risks 
Any relapse to illicit opioid and other drug and alcohol use among any of the two treatment 
arms after release from jail (or while incarcerated) implies a risk of death and disability, and 
some proportion of participants in all three arms can be expected not to respond to 
treatment and resume opioid and/or other drug and alcohol use. All participants relapsing 
post-release and struggling with on-going drug and alcohol use will be counseled and 
referred by staff to any appropriate treatment modalities, including the immediately available 
addiction services available at Bellevue Hospital (emergency detoxification with referral to 
residential treatment or supportive housing, methadone treatment, buprenorphine, intensive 
outpatient, dual diagnosis). 
Sublingual Buprenorphine-Naloxone Treatment Arm. The risks of SLB are the usual risks 
experienced by any patient as part of standard of care buprenorphine maintenance, which is 
first-line treatment for opioid use disorders in NYC jails and in the community. Persons 
receiving SLB may experience several common side effects such as drowsiness, dizziness, 
constipation, or headaches. The SLB arm will otherwise not be exposed to risks beyond 
those of usual care, which will be provided by existing jail and community partners. Further, 
participants in the SLB arm will have already agreed to these risks and benefits of an SLB 
treatment program prior to recruitment and enrollment, as their choice to engage in jail SLB 
will have been established well before enrollment, which will occur at the end of the 
incarceration period. 
Buprenorphine Extended-Release Treatment Arm. XRB carries the same potential systemic 
buprenorphine-related side effects as SRB. XRB also carries risks from the injection. 
Injection site soreness is possible and usually well tolerated. More severe injection site 
reactions, although rare, include swelling, itching, and pain. All injections sites will be 
inspected and monitored by study clinicians. 
Concomitant use of buprenorphine and benzodiazepine or other CNS depressants 
increases the risk of adverse reactions including overdose, respiratory depression, and 
death. Urine toxicology biometric tests will be used to ensure persons receiving both SLB 
and XRB have not taken any other substances. Participants will be educated regarding the 
risks of concomitant use of benzodiazepines, sedatives, opioid analgesics and alcohol. 
Additionally, if a participant requires opioids for any medical treatment once on 
buprenorphine, they will likely not have adequate pain relief from usual doses of opioid pain 
medications. Participants should tell the treating clinician that they are participating in this 
clinical study and will need non-opioid pain relief or higher doses of opioid pain medications 
for their condition, which they should receive only in a monitored medical setting, such as an 
emergency room. As a result, participants may experience higher level of pain. 
Risk/Benefit Ratio: Most of the risks described are expected adverse events associated with 
XRB and SLB, or those of baseline opioid dependence and jail-to-community ETAU or MTP. 
The risks of the active treatment arms, XRB and SLB are likely small compared to the 
expected benefit of discontinuing opioid use. 


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4 - Study Objectives 
4.1 Hypothesis 
Primary Aim hypothesis: We hypothesize that XRB will be a feasible, effective, and 
preferred/accepted medication assisted therapy for OUDs in jail as compared to SLB. 
Secondary Aim 1 hypothesis: We hypothesize that XRB will be more effective in improving 
rates of community treatment initiation/continuation post-release as compared to SLB. 
Secondary Aim 2 Hypothesis: We hypothesize that XRB will be more effective in decreasing 
illicit opioid use post-release as compared to SLB. 
Secondary Aim 3 Hypothesis: We hypothesize that the use of XRB vs. SLB will lead to 
better outcomes in the context of XRNTX, ETAU, and Methadone outcomes accrued in the 
larger SOMATICS-XOR RCT. 
4.2 Primary Objective 
Feasibility and Implementation: Estimate the feasibility and ease of use of XRB vs. SLB as 
measured by initial patient preference and acceptability, in-treatment patient satisfaction, 
patient qualitative interviews, jail visit frequency and program cost estimates, and rates of 
medication diversion. 
4.3 Secondary Objectives 
Treatment Retention: Estimate the effectiveness of XRB vs. SLB in improving rates of 
community treatment initiation/continuation post-release. 
Clinical Effectiveness: Estimate the effectiveness of XRB vs. SLB in decreasing illicit opioid 
(e.g. heroin) use post-release. 
Naturalistic Comparative Effectiveness: Evaluate outcomes of XRB vs. SLB in the context of 
the XRNTX, ETAU, and Methadone outcomes accrued in the larger SOMATICS-XOR RCT. 


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5 - Study Design 
5.1 General Design 
This is a phase IV, 8 week, pilot proof-of-concept randomized controlled trial, open-label and 
unblinded of XRB vs SLB (N=50) that takes advantage of the existing SOMATICS-XOR U01 
(NIDA) trial design. 
5.1.1 Study Duration 
This is an 8 week pilot RCT. 
The study has received 50 doses of in-kind SublocadeTM study medication from the 
manufacturer, Indivior as of September 13, 2019. With this new stock of medication, we 
would like to offer all participants the option of a therapeutic treatment extension of 24 
weeks post study visit 5 week 8. Active treatment will continue after the Week 8 study visit 
through Week 20 wherein participants will be eligible to receive initial and/or additional XRB 
injections. A safety visit, in which no medication is administered, will be conducted at Week 
24 to document safety reporting and provide post-study treatment referrals. 
This 24 week therapeutic extension will be offered to all interested participants regardless of 
their treatment assignment after the completion of Visit 5 Week 8. Only SublocadeTM 
injections will be offered, no additional forms of compensation will be provided.  
5.1.2 Number of Study Sites 
This is a multi-site pilot, RCT. Participants (N=50) will be recruited from Rikers Island NYC 
Jail and will then complete all follow-up visits at Bellevue Hospital Center in NYC. The NYU 
School of Medicine Institutional Review Board (IRB) is serving as the IRB of record for 
Health+Hospitals involvement in this research study.  
Sites: The NYC jail system houses approximately 8,000-9,000 inmates daily in 11+ inmate 
facilities, 8 of which are located on Rikers Island. Most (90%) are adults detained on  
charges or sentenced to misdemeanor charges and likely to leave jail and return to the 
community following an average pretrial detention of several weeks or after serving a 
misdemeanor sentence of less than one year. The jail Opioid Treatment Program primarily 
operates at three facilities, a male admission facility (Anna M Kross Center), a male 
sentenced-inmate facility (Eric M Taylor Center), and a single female facility (Rose M Singer 
Center), all located on Rikers Island in the Bronx. For the purposes of this pilot, participants 
will be recruited from the Eric M Taylor Center and the Rose M Singer Center. The jail 
Opioid Treatment Program currently treats around 100-200 patients daily with sublingual 
buprenorphine, this pilots target population, and 500-800 daily with methadone maintenance. 
All  follow-up  will  be  conducted  at  the  Bellevue  Hospital  Center's  Adult  Primary                 
Care Clinic and its Addiction Medicine clinic, which is currently a routine aftercare referral for 
jail patients continuing buprenorphine in the community and the site of the current NYU- 
NIDA U01 XOR trial. Patient’s lost-to-follow-up and out-of-contact are tracked by study staff 
in the community whenever possible, including in-person door-knocking by Study Staff 
throughout the 5 boroughs and northern New Jersey. 
5.2.1 Primary Outcome Variables 
The primary outcome of in-jail feasibility and acceptability will be measured by the percent of 
eligible participants who enroll in the study, the mean medical/medication visits per arm and 


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per participant, rates of medication diversion, and open-ended interviews with patients 
regarding treatment satisfaction and ease of use. Additional qualitative interviews will be 
conducted with eligible participants to further examine opioid use disorder treatment with 
extended-release buprenorphine, in-jail and within the community.  
5.2.2 Secondary and Exploratory Outcome Variables 
Secondary Aims 1-3 will be measured utilizing the following assessments: baseline 
demographics, baseline ASI-Lite, baseline MOUD (medication treatment for opioid use 
disorder) exposure/preference, Timeline Followback, urine toxicology results, treatment 
retention, and NYS Prescription Monitoring Data. XRNTX, ETAU, and Methadone outcomes 
will be taken from the SOMATICS-XOR U01 parent study. 
5.3 Study Population 
Adult jail inmates with upcoming release date, current opioid dependence and currently 
maintained on sublingual buprenorphine-naloxone (N=50). 
5.3.1 Number of Participants 
N=50. A total sample size of N=50 would allow for an estimate of an Odds Ratio of 2.0-3.0 
for the rate of persons successfully in community buprenorphine treatment at 4 weeks post- 
release (71% vs. 30% success favoring XRB; two-sided alpha of 0.05; 80+% power). 
5.3.2 Eligibility Criteria/Vulnerable Populations 
Inclusion criteria 
1) Adults >18yo incarcerated in NYC jails with known release dates. 
2) DSM-V criteria for current opioid use disorder (DSM-IV opioid dependence). 
3) Currently maintained on sublingual buprenorphine-naloxone in the NYC jail opioid 
treatment program. 
Exclusion Criteria 
1) Individual not interested in XRB treatment. Current SLB patients are otherwise by 
definition appropriate for XRB. 
2) Pregnant or planning conception. As female participants are incarcerated & active in the 
jail opiate treatment program at the time of baseline assessments and treatment induction, a 
pregnancy test is not required by the study staff. A urine dipstick pregnancy (hCG) test will 
be administered at week 4 visit 3. The test detects human chorionic gonadotropin (hCG) in 
urine with a sensitivity/specificity of: 25 mIU hCG/ml, >99%. Time to result is four minutes. If 
negative, a urine pregnancy test will be administered at the final week 8 visit 5 and final week 
20 visit 8 (if applicable) to ensure that a participant is not pregnant. 
3) No severe or acute medical or psychiatric disability preventing safe study participation or 
making follow-up unlikely. 
Federal Research among Prisoners. Study participants are clearly considered prisoners at 
the time of enrollment.  The NYU SOM IRB will contact DHS/OHRP to address this topic 
and for permission to enroll prisoners in a federally funded research trial. However, we 
believe this study carefully conforms to the Federal guidelines for research among prisoners 
(CFR 46.306) in the following manner: 


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1.) Research on practices, both innovative and accepted, which have the intent and 
reasonable probability of improving the health or well-being of the subject. In cases in which 
those studies require the assignment of prisoners in a manner consistent with protocols 
approved by the IRB to control groups which may not benefit from the research, the study 
may proceed only after the Secretary has consulted with appropriate experts, including 
experts in penology medicine and ethics, and published notice, in the Federal Register, of 
his intent to approve such research. 
2) Any possible advantages accruing to the prisoner through his or her participation in the 
research, when compared to the general living conditions, medical care, quality of food, 
amenities and opportunity for earnings in the prison, are not of such a magnitude that his or 
her ability to weigh the risks of the research against the value of such advantages in the 
limited choice environment of the prison is impaired. Incentives and benefits from 
participation are not coercive and are fair value of participant's time and, following release, 
travel. 
(3) The risks involved in the research are commensurate with risks that would be accepted 
by non-prisoner volunteers. This study's methods and interventions are consistent with good 
clinical practices in community settings. 
(4) Procedures for the selection of subjects within the prison are fair to all prisoners and 
immune from arbitrary intervention by prison authorities or prisoners. Unless the principal 
investigator provides to the Board justification in writing for following some other procedures, 
control subjects must be selected randomly from the group of available prisoners who meet 
the characteristics needed for that particular research project. Jail authorities have no role in 
this study or in treatment assignment, which is random. 
(5) The information is presented in language which is understandable to the subject 
population. The informed consent and consent quiz are intended to be understandable to 
adults in jail. 
(6) Adequate assurance exists that parole boards will not take into account a prisoner's 
participation in the research in making decisions regarding parole, and each prisoner is 
clearly informed in advance that participation in the research will have no effect on his or her 
parole; There is no role for, relationship, or other interaction with parole or probation 
authorities and this study. 
(7) Where the Board finds there may be a need for follow-up examination or care of 
participants after the end of their participation, adequate provision has been made for such 
examination or care, taking into account the varying lengths of individual prisoners' 
sentences, and for informing participants of this fact. The study primarily consists of 
community follow-up of adults released from NYC jails. Follow-up  consists of research 
visits conducted weekly then bi-weekly for both medication arms post-release (week 1 post- 
release, week 2, week 4, week 6, week 8). After the completion of Visit 5 Week 8, all 
participants will be eligible for a 24 week therapeutic extension study wherein they are 
offered initial and/or additional XRB injections. These will occur monthly post study week 8: 
week 12, week 16, week 20, week 24, and week 28. A final safety visit, no medication 
administered, will be conducted at week 32 to document safety reporting and provide post-
study treatment referrals.  


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6 - Methods 
6.1.1 Identity of Investigational Product/New Drug 
Monthly, injectable, buprenorphine extended-release (XRB, SublocadeTM, Indivior) is the 
most recently FDA approved pharmacotherapy for opioid use disorders in the U.S.(2). XRB 
is available as of March-2018 in a pre-mixed subcutaneous formulation, administered 
monthly, and equivalent to a 16-24mg/day maintenance dose of sublingual buprenorphine- 
naloxone (SLB). Sublingual buprenorphine was approved by the FDA in 2002 and is 
delivered daily by placing the medication under the tongue for 5 to 10 minutes and letting it 
dissolve completely. 
6.1.2 Dosage, Admin, Schedule 
Buprenorphine Extended Release: XRB is a 300mg or 100mg pre-mixed subcutaneous 
injectable formulation to be administered monthly. XRB is for abdominal subcutaneous 
injection only. Participants in the XRB treatment arm will be given 1 or more XRB injections 
prior to release from jail and one or more at weeks 4, 8, 12, and 16 post-release, depending 
on their release date. 
Sublingual Buprenorphine: SLB (SUBOXONE, Zubsolv, or generic tablets) is a daily 
sublingual film or tablet ranging from 8-24mg/day or equivalent (Zubsolv is dosed 5.7-17.1 
mg/day). The film or tablet is placed under the tongue for 5 to 10 minutes until dissolved 
completely. Participants in the SLB treatment arm will be provided SLB daily by observed 
dosing in-jail (controlled substances are not self-administered in-jail) and encouraged to 
continue SLB treatment in weekly, bi-weekly, or monthly quantities for unobserved, daily, 
self-administration through week 5. Patients may obtain SLB care free-of-charge from the 
Bellevue Hospital Center Addiction Medicine clinic or from non-NYU/Bellevue providers and 
pharmacies per usual care standards. After the completion of Visit 5 Week 8, SLB 
participants will be offered XRB treatment in the 20 week therapeutic extension. If 
interested, participants would receive one or more XRB injections during the period of 
Weeks 8, 12, 16, 20, 24, and 28 followed by a final safety documentation visit at Week 32. 
6.1.3 Method of Assignment/Randomization 
Screening and Randomization 
This pilot will recruit from within the standard-of-care NYC jail opioid treatment program, led 
by the program director, Jonathan Giftos, MD. Potential participants currently maintained on 
sublingual buprenorphine (currently a NYC jail standard of care) will be offered study 
information and encouraged to enroll. Interested participants will be referred by the Opioid 
Treatment Program staff to Study Staff for further education about the trial and to schedule 
written informed consent and a comprehensive screening visit. Consented and eligible 
participants will be randomized by sealed envelope or a web-based randomizer 1:1 to the 2 
study cells: XRB and SLB. 
6.1.4 Blinding and Procedures for Unblinding 
This is an 8-week, open-label, single site, proof-of-concept randomized controlled trial. 
There is no blinding of treatment assignment or of outcomes assessments. 


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6.1.5 Packaging/Labeling 
Buprenorphine Extended Release (SUBLOCADE): XRB is available in dosage strengths of 
100 mg/0.5 mL and 300 mg/1.5 mL buprenorphine. Each dose is provided in a prefilled 
syringe with a 19 gauge 5/8-inch needle. The recommended dose of XRB following 
induction and dose adjustment with transmuscosal buprenorphine is 300 mg monthly for the 
first two months followed by a maintenance dose of 100 mg or 300mg monthly. We will offer 
both 300mg and 100mg doses pre-release and at week 4 post-release.  Each dose is 
supplied in an individual kit and will be acquired in bulk shipments from the supplier Indivior. 
At the outset of this study and original IRB approval, it was proposed that each participant 
randomized to the XRB (SUBLOCADE) treatment arm would receive up to two injections of 
XRB, each 300mg according to the medication package insert. However, the study has 
since been modified to include a therapeutic treatment extension of 24 additional weeks 
post Visit 5 Week 8 in which initial and/or additional XRB injections would be offered to all 
interested participants (see section 5.1.1). With this therapeutic extension, eligible & 
interested participants could receive 4+ XRB injections in the community. With this in mind, 
the study must expand the planned XRB dosage to include the 100mg formulation of XRB. 
As the XRB package insert states, the recommended dose of XRB following induction is 
300mg monthly for the first two months followed by a maintenance dose of 100mg or 
300mg monthly. The study must have the capability to offer eligible participants receiving a 
third XRB injection the lower, recommended maintenance dose of 100mg in addition to the 
standard 300mg.  
Sublingual Buprenorphine (SUBOXONE, Zubsolv, or generic tablets): SLB is administered 
sublingually or buccally as a single daily dose. Medication should be prescribed in 
consideration of the frequency of visits. Provision of multiple refills is not advised in early 
treatment or without appropriate follow-up visits. After treatment induction and stabilization, 
the maintenance dose of SLB is generally in the range of 4mg/1mg buprenorphine/naloxone 
to 24mg/6mg buprenorphine/naloxone per day depending on the individual patient and 
clinical response, as determined by the clinician. Daily doses will vary by individual. The 
recommended target dose of SLB during maintenance is 16mg/4mg 
buprenorphine/naloxone. SLB will be prescribed and provided via observed dosing in-jail 
(controlled substances are not self-administered in-jail) per usual care protocols. Post- 
release, all participants may elect to continue SLB maintenance with the Bellevue Primary 
Care Addiction Medicine clinic, or may pursue SLB maintenance from non-NYU/Bellevue 
community providers. SLB is available free of charge to uninsured patients at Bellevue 
Hospital Center, or participants may fill SLB prescriptions at community pharmacies. SLB 
medication will not be provided by the study itself. Self-report, BHC EMR records, and NYS 
Prescription Monitoring Plan audits will document SLB post-release community treatment 
retention, daily dose, and refill frequencies. 
6.1.6 Storage Conditions 
XRB Storage Conditions: Store refrigerated at 2 - 8ºC (35.6 - 46.4ºF). Once outside the 
refrigerator XRB may be stored in its original package at room temperature 15-30ºC (59 - 
86ºF), for up to 7 days prior to administration. 
SLB Storage Conditions: Store at room temperature between 20 - 25ºC (68 - 77ºF). 
6.1.7 Concomitant therapy 


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It is advisable for both XRB and SLB treatment arms that patients refrain from use of 
benzodiazepines, sedatives, tranquilizers, antidepressants, stimulants, or alcohol. Urine 
toxicology will be collected at medication dispensation visits in order to ensure no 
contraindications. 
6.1.8 Restrictions 
XRB Restrictions: For abdominal subcutaneous injection only. Do not administer XRB 
intravenously or intramuscularly. Only a healthcare provider should prepare and administer 
XRB. Administer monthly with a minimum of 26 days between doses. 
SLB Restrictions: Take the prescribed dose once a day. SLB must be taken whole. Do not 
cut, chew, or swallow. SLB film should not be moved after placement. Proper administering 
technique should be demonstrated to the patient by a healthcare provider. 


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6.2 Assessments 
Measures and Assessments: 
a) Baseline assessments include a drug and alcohol use history (ASI-Lite), a pre-arrest  
recall of drug and alcohol use (Timeline Followback), a medication treatment for opioid use 
disorder exposure/preference form (MOUD preference), demographic information, and jail 
Electronic Medical Record medical and psychiatric history and laboratory data, including HIV 
and HCV status. 
b) In-jail feasibility assessments of XRB vs. SLB include logging the % eligible enrolling in 
the study; the density of medical/nursing/pharmacy visits per arm and per participant; the 
incidence rates of medication diversion; open-ended interviews with participants surrounding 
XRB vs. SLB and ease-of-use and satisfaction; 
a) Post-release follow-up assessments include administrative data for SLB medication refills 
and post-release XRB injections, self-reported opioid and other drug use (Timeline 
Followback), urine toxicology testing, pregnancy testing, treatment retention (treatment 
retention form), Adverse Event and Serious Adverse Event monitoring (SAFTEE), and NYS 
Prescription Monitoring Data for community SLB pharmacy refill reporting. The I-STOP/PMP 
(prescription monitoring program) registries will be accessed in order to track participant 
data related to respective treatments. Additional qualitative interviews will be conducted with 
eligible XRB participants to further examine opioid use disorder treatment with extended-
release buprenorphine, in-jail and within the community. 
6.2.1 Efficacy 
The primary outcome of in-jail feasibility and acceptability will be measured by the percent of 
eligible participants who enroll in the study, the mean medical/medication visits per arm and 
per participant, the incidence rates of medication diversion, and open-ended interviews with 
patients regarding treatment satisfaction and ease of use. 
Secondary Aims 1-3 will be measured utilizing the following assessments: baseline 
demographics, baseline ASI-Lite, baseline MOUD exposure/preference,  Timeline 
Followback, urine toxicology results, treatment retention, and NYS Prescription Monitoring 
Data. XRNTX, ETAU, and Methadone outcomes will be taken from the SOMATICS-XOR 
U01 parent study. 
6.2.2 Safety/Pregnancy-related policy 
XRB and SLB are both FDA approved, safe, efficacious medications for the treatment of 
opioid use disorder. As with most medications both XRB and SLB carry side effects as 
detailed above. Participants will be monitored throughout this pilot RCT by study physicians, 
all adverse events and/or serious adverse events will be documented and medication will be 
discontinued if necessary. Women who are pregnant or plan to become pregnant will be 
excluded from this pilot RCT. 
6.2.2.1 Adverse Events Definition and Reporting 
For the purposes of this pilot, proof-of-concept, RCT, an adverse event (AE) is any 
symptom, sign, illness or experience that develops or worsens in severity during the course 
of the study. Intercurrent illnesses or injuries should be regarded as adverse events. 


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Abnormal results of diagnostic procedures are considered to be adverse events if the 
abnormality: 
• 
results in study withdrawal 
• 
is associated with a serious adverse event 
• 
is associated with clinical signs or symptoms 
• 
leads to additional treatment or to further diagnostic tests 
• 
is considered by the investigator to be of clinical significance (i.e. medication side 
effects) 
All adverse events will be documented in the attached clinical research form and reported to 
the IRB where necessary. 
A serious adverse event (SAE) is any AE that is: 
• 
fatal 
• 
life-threatening 
• 
requires or prolongs hospital stay 
• 
results in persistent or significant disability or incapacity 
• 
a congenital anomaly or birth defect 
• 
an important medical event 
Important medical events are those that may not be immediately life threatening, but are 
clearly of major clinical significance. They may jeopardize the subject, and may require 
intervention to prevent one of the other serious outcomes noted above. For example, drug 
overdose or abuse, a seizure that did not result in in-patient hospitalization, or intensive 
treatment of bronchospasm in an emergency department would typically be considered 
serious. 
All serious adverse events will be documented in the attached clinical research form and 
reported to the IRB where necessary. 
Classification of an Adverse Event: for AEs in this pilot RCT the following guidelines will be 
used to describe severity. 
• 
Mild — Events require minimal or no treatment and do not interfere with the 
participant's daily activities. 
• 
Moderate — Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
functioning. 
• 
Severe — Events interrupt a participant's usual daily activity and may require 
systemic drug therapy or other treatment. Severe events are usually potentially life- 
threatening or incapacitating. 


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Relationship to Study Medication: To assess whether an AE may be associated with the 
study medication (XRB vs. SLB) the following guidelines will be used: 
 
 
• 
Definitely Related — There is clear evidence to suggest a causal relationship, and 
other possible contributing factors can be ruled out. The clinical event, including an 
abnormal laboratory test result, occurs in a plausible time relationship to drug 
administration and cannot be explained by concurrent disease or other drugs or 
chemicals. The response to withdrawal of the drug (dechallenge) should be clinically 
plausible. The event must be pharmacologically or phenomenologically definitive, 
with use of a satisfactory rechallenge procedure if necessary 
• 
Probably Related — There is evidence to suggest a causal relationship, and the 
influence of other factors is unlikely. The clinical event, including an abnormal 
laboratory test result, occurs within a reasonable time after administration of the 
drug, is unlikely to be attributed to concurrent disease or other drugs or chemicals, 
and follows a clinically reasonable response on withdrawal (dechallenge). 
Rechallenge information is not required to fulfill this definition. 
• 
Possibly Related — There is some evidence to suggest a causal relationship (e.g., 
the event occurred within a reasonable time after administration of the trial 
medication). However, other factors may have contributed to the event (e.g., the 
participant's clinical condition, other concomitant events). Although an AE may rate 
only as "possibly related" soon after discovery, it can be flagged as requiring more 
information and later be upgraded to "probably related" or "definitely related," as 
appropriate. 
• 
Unlikely to be related — A clinical event, including an abnormal laboratory test result, 
whose temporal relationship to drug administration makes a causal relationship 
improbable (e.g., the event did not occur within a reasonable time after  
administration of the trial medication) and in which other drugs or chemicals or 
underlying disease provides plausible explanations (e.g., the participant's clinical 
condition, other concomitant treatments). 
• 
Not Related — The AE is completely independent of study drug administration, 
and/or evidence exists that the event is definitely related to another etiology. There 
must be an alternative, definitive etiology documented by the clinician. 
Study clinicians will be responsible for determining whether an AE is expected or 
unexpected. An AE will be considered unexpected if the nature, severity, or frequency of the 
event is not consistent with the risk information previously described for the study agent. 
The pilot study team will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the 
last day of study participation. At each study visit, the investigator will inquire about the 
occurrence of AE/SAEs since the last visit. Events will be followed for outcome information 
until resolution or stabilization. 


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6.2.3 Pharmacokinetics 
Not applicable. 
6.2.4 Biomarkers 
Not applicable. 
6.3 Study Procedures 
The study procedures are detailed below. 
6.3.1 Study Schedule 
The total number of expected visits per participant is 6 visits. All participants will be given 
the option to participate in a 24 week therapeutic extension study of XRB treatment 
following completion of Visit 5 Week 8. If a participant elects to continue and/or initiate XRB 
treatment, there will be 12 total visits per participant. The average time needed to complete 
each visit will be approximately one hour. The initial week 0 screening and randomization 
visit will be conducted in a Rikers Island jail facility in the Opioid Treatment Program. Once 
consented, enrolled, and randomized, buprenorphine extended-release (XRB) or sublingual 
buprenorphine (SLB) daily maintenance will provided per usual Opioid Treatment Program 
protocols in-jail and prior to release. The timing between randomization and release will 
vary. Typical misdemeanor sentences in NYC are 30-60 days, and participants may 
randomize at any time during this incarceration period, begin XRB vs. SLB treatment, and 
then leave jail after weeks-to-months. This variable, naturalistic, in-custody study period 
remains Study Week 0.  Study Week 1 commences with the day of release from jail. Post-
release, all study visits will be conducted at Bellevue Hospital Center's (BHC) Addiction 
Medicine clinic. Medical and research visits will be conducted weekly and then bi- weekly for 
both medication arms post-release (week 1 post-release, week 2, week 4, week 6, week 8). 
The medication schedule for both arms is as follows: 
Buprenorphine Extended-Release: Participants randomized to this arm will receive at least 
two doses of XRB. The first will be administered at study week 0 in-jail, at least one week 
prior to release. Participants incarcerated for greater than 4 weeks following randomization 
will receive 2+ XRB doses prior to release. Post-release, XRB injections will be administered 
at study week 1-16 in the BHC Addiction Medicine clinic depending on the timing of the 
previous pre-release/community  injections. 
Sublingual Buprenorphine: Participants randomized to this arm will be provided SLB daily 
maintenance per usual Opioid Treatment Programs protocols in-jail. Post-release, SLB arm 
participants will receive follow-up care at Bellevue Hospital’s Addiction Medicine or at non- 
BHC/NYU community providers, per their preference. We expect and will encourage most 
participants to follow-up at Bellevue, though this is not mandated. Typically an initial week's 
supply of SLB is prescribed within one week of release. At visit 2, week 2, SLB participants 
typically refill a two week's supply of daily maintenance SLB. SLB participants will continue 
to receive 2-4 week refill prescriptions for SLB from visit 2, week 2 through visit 6, week 8. 
Regardless of SLB prescribing patterns, they are encouraged to attend study follow-up visits 
at BHC per the same study schedule (Weeks 1,2,4,6,8). After the completion of Visit 5 
Week 8, SLB participants will be offered XRB treatment in the 24 week therapeutic 
extension. If interested, participants would receive one or more XRB injections during the 


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period of Weeks 8, 12, 16, 20, 24, and 28 followed by a final safety documentation visit at 
Week 32. 
For both treatment arms, urine toxicology tests will be conducted at all follow-up visits at the 
BHC Addiction Medicine Clinic in order to detect any illicit substance use as well as 
buprenorphine adherence. 


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STUDY SCHEDULE 
Test/Procedures 
Screening/ 
Randomization 
Treatment Period & Follow-Up 
XRB 20 Week Treatment & Follow-Up 
Study Visit Number 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Week 
0 
1 
2 
4 
6 
8 
12 
16 
20 
24 
28 
32 
Informed Consent 1 
X 
HIPAA 2 
X 
Locator Form 
X 
Medical History 
X 
Psychological History 
X 
Physician Progress Note 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Confirm Eligibility 
X 
Randomization 
X 
 
Adverse Event Forms 
(AE, SAE, BUP 
specific AE) 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
Clinical Assessment 
of Intervention 3 
 
X 
 
 
 
 
 
X 
Urine Toxicology 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Test 
 
 
 
X 
 
X 
 
X 
 
 
X 
 
Demographics 
X 
MOUD 
History/Preference 
X 
ASI-Modified 
Lifetime/CJS-Baseline 
X 
Timeline Followback 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Inmate Lookup Form4 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
New Arrests and Days 
Incarcerated Form4 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Overdose Form 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
XR-B Administration 
Form 
X 
 
 
X 
 
 
X 
X 
X 
X 
X 
 


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NYS Prescription 
Monitoring Data 
(SLB- Only) 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
Dispense 
Study 
Medications5 
X, # 
X, # 
X, # 
X, # 
X, # 
X 
X 
X 
Treatment Retention 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Open-
Ended 
Interviews6 
X 
 
 
 
X 
 
 
 
 
 
 
Qualitative 
Interviews7 
 
 
 
 
X 
 
X 
X 
 
X 
 
Treatment 
Satisfaction 
Form 
 
X 
 
 
 
 
 
X 
Annotations: 
1. 
All patients must sign an informed consent consistent with ICH-GCP guidelines prior to 
participation in this trial, which includes performing any screening procedures, medication 
washout and any restrictions. 
2. 
HIPAA authorization must be obtained on all patients participating in the study at Visit1. 
3. 
Clinical Assessment must be completed per protocol instructions and by the treating 
investigator for that specific patient. 
4. 
These instruments will be available for each visit, however they may/may not be filled out   
       depending on participant’s interaction with CJS 
5.    X = XRB, # = SLB; dispensation schedule varies depending on release date 
6.    Open-Ended interview should occur at participant’s first & final community visit 
7.    For eligible XRB participants only, occurs at week 8 and final community visit.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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6.3.2 Informed Consent 
Potential participants interested in buprenorphine maintenance (currently a NYC jail 
standard of care) will be offered study information and encouraged to enroll. The study 
team will receive IRB-approval for all study documents, informational handouts, informed 
consent forms, informed consent quizzes, and all CRFs prior to screening and 
randomizing participants. Consent forms describing in detail the study agent, study 
procedures, and risks are given to the participant and written documentation of informed 
consent is required prior to starting intervention/administering study product. Written 
informed consent including a consent quiz adapted from the parent grant protocol will be 
used to document informed consent. Participants will have the opportunity to carefully 
review the written consent form and ask questions prior to signing. The participants may 
withdraw consent at any time throughout the course of the trial. A copy of the signed 
informed consent document will be given to the participants for their records. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality 
of their medical care will not be adversely affected if they decline to participate in this 
study. 
A copy of the signed informed consent document will be stored in the subject's research 
record. The consent process, including the name of the individual obtaining consent, will be 
thoroughly documented in the subject's research record. Any alteration to the standard 
consent process (e.g. use of a translator, consent from a legally authorized representative, 
consent document presented orally, etc.) and the justification for such alteration will likewise 
be documented. 
6.3.3 Screening 
Potential participants will meet with study staff to learn about study procedures, 
buprenorphine (XRB and SLB) treatment, and follow-up protocols. A pre-screen checklist 
will evaluate eligibility. All adult jail inmates with an upcoming release date, current opioid 
use disorder diagnosis, and currently maintained on sublingual buprenorphine-naloxone will 
be potential participants. If interested and eligible, participants will complete the informed 
consent process (ICF and ICF quiz). Once informed consent is obtained, baseline 
assessments will be administered prior to randomization. The baseline assessments include 
a drug and alcohol use history (ASI-Lite), demographics, a pre-arrest recall of drug and 
alcohol use (Timeline Followback), prior medication treatment for opioid use disorder 
exposure and preferences (MOUD Preference form), and jail Electronic Medical Record 
medical and psychiatric history and laboratory data, including HIV and HCV status. 
6.3.4 Recruitment, Enrollment and Retention 
Recruitment: Adult inmates with known Department of Corrections release dates and recent 
or on-going opioid treatment are housed in two NYC jail facilities, both on Rikers Island; the 
Eric M. Taylor Center (male) and the Rose M Singer Center (female). Approximately 150 
persons a month leave this facility with an opioid use disorder diagnosis and on active OUD 
treatment (e.g. buprenorphine, methadone, naltrexone, or counseling). NYULMC study staff 
with NYC Health+Hospitals clinical credentials and HHC-approved access to Rikers 
electronic medical record database (EMR) will search for opioid dependent diagnoses, in-jail 
opioid treatment program participation and pending release dates of potential participants 


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located in this housing unit. Potential participants interested in buprenorphine maintenance 
(currently a NYC jail standard of care) will be offered study information and encouraged to 
enroll. As current daily maintenance of sublingual buprenorphine is required in order to be 
eligible for this pilot, participants will be already be affiliate with the in-jail Opioid Treatment 
Program and will be referred by the Opioid Treatment Program staff to Study Staff for further 
education about the trial and to schedule written informed consent and a comprehensive 
screening visit. Monetary compensation for time and travel are intended to facilitate and 
encourage follow-up visit attendance; transportation services for follow-up visits are 
otherwise not provided.  
 
Informed Consent and Enrollment/Randomization: Study staff will obtain informed consent 
via the completion of the informed consent form and informed consent quiz. Consented and 
eligible participants will be randomized by sealed envelope or a web-based randomizer 1:1, 
XRB vs. SLB. Medications will be dispensed at the screening/randomization visit in-jail (visit 
1, week 0) for both arms. All follow-up visits (visit 1-6) will take place at Bellevue Hospital 
Center's Addiction Medicine clinic and medication (XRB) will be provided free-of-charge. 
6.3.5 On Study Visits 
Screening and Randomization (~1.5 hours): 
 
• 
Informed Consent & Informed Consent Quiz 
• 
Baseline assessments: 
o Drug and alcohol use history (ASI-Lite) 
o Pre-arrest recall of drug and alcohol use (Timeline Followback) 
o Prior Medication Treatment for Opioid Use Disorder exposure & preferences 
(MOUD Preference form) 
o Jail Electronic Medical Record medical and psychiatric history & laboratory 
data, including HIV and HCV status 
• 
Randomization envelope opened & completed by study staff and participant 
o Medication dispensed (XRB or SLB) 
o Additional in-jail injections of XRB may occur if participant is incarcerated for 
over 4 weeks. 
Follow-Up Visits (v1-4, ~1 hour) 
 
• 
Administrative data for SLB medication refills and post-release XRB injections 
• 
Self-reported opioid and other drug use (Timeline Followback) 
• 
Urine specimen collection and toxicology testing 
• 
Adverse Event and Serious Adverse Event monitoring (SAFTEE) 
• 
NYS Prescription Monitoring Data for community SLB pharmacy refill reporting 
o I-STOP/PMP Registry 
• 
Treatment Retention Form completed  
• 
At visit 1 week 1, open-ended interview will be administered. 


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• 
At visit 3 week 4, second XRB administered, depending on prior injection date. 
• 
At visit 3 week 4, pregnancy test will be administered.. 
Research Visit 5 Week 8 (Final Visit, ~1 hour): 
 
• 
Medication is not dispensed 
• 
For participants electing to continue in the 24 week extension, initial and/or additional 
XRB injection could be administered at this time point 
• 
Self-reported opioid and other drug use (Timeline Followback) 
• 
Urine specimen collection and toxicology testing 
• 
Pregnancy testing 
• 
Treatment Retention completed 
• 
Treatment Satisfaction completed 
• 
Adverse Event and Serious Adverse Event monitoring (SAFTEE) 
 
• 
NYS Prescription Monitoring Data for community SLB pharmacy refill reporting 
o I-STOP/PMP Registry 
• 
Open-ended interview with participants concerning XRB vs. SLB treatment 
satisfaction and ease-of-use 
Treatment Visit 6-10 Week 12,16, 20, 24, 28 (~1 hour): 
• 
24 Week Extension Participants Only: 
o Self-reported opioid and other drug use (Timeline Followback) 
o Urine specimen collection and toxicology testing 
o Adverse Event and Serious Adverse Event monitoring (SAFTEE) 
o XRB administered, depending on prior injection date. 
o At visit 7 week 16 and visit 10 week 28, pregnancy test will be 
administered 
o Qualitative Interviews (randomized to XRB treatment arm only) will 
be conducted at XRB injection treatment visits depending on 
participants’ medication schedules. 
Safety Visit 11 Week 32 (~1 hour, final visit): 
o Self-reported opioid and other drug use (Timeline Followback) 
o Adverse Event and Serious Adverse Event monitoring (SAFTEE) 
o Qualitative Interviews if applicable 
o Treatment Satisfaction form 
In-Jail Feasibility: 
 


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• 
Assessments of XRB vs. SLB 
o Logging the % eligible enrolling in the study 
o The density of medical/nursing/pharmacy visits per arm and per participant 
o Rates of medication diversion. 
6.3.6 End of Study and Follow-up 
After completion of the final visit (Visit 5, Week 8), study participation is complete for all 
participants who do not elect to continue and/or initiate treatment in the 24 week 
therapeutic extension of XRB treatment. All participants will be provided information on XRB 
and SLB and will be encouraged to continue treatment with the community opioid treatment 
provider of their choice. All participants will have the option of accessing services at 
Bellevue, including buprenorphine and methadone maintenance treatment. It is likely that 
the majority of participants in both arms will continue on SLB maintenance with the BHC 
Addiction Medicine clinic. XRB may become a usual care option at BHC during the course 
of this trial, depending on NYS Medicaid policies and H+H formulary updates. 
For participants who continue in the 24 week therapeutic extension, after completion of the 
final safety visit (Visit 11, Week 32), study participation is complete. All participants will be 
provided the same information as highlighted above. It is likely that the majority of 
participants in this arm will continue on SLB maintenance with the BHC Addiction Medicine 
clinic. 
In-jail feasibility will be assessed during and post study completion as the data is made 
available. All adverse event and serious adverse event monitoring (SAFTEE) will take place 
throughout the study and will be documented/reported as necessary. 
6.3.7 Removal of subjects 
Participation in this pilot, proof-of-concept, RCT is entirely voluntary and participants are free 
to withdraw at any time. In the event of early study termination, study staff will complete the 
study termination form, modeled from a CRF of the parent XOR study. Any participant 
withdrawing from the study prior to full study completion, regardless of study group, stands a 
risk of relapsing to illicit opioid or other drug/alcohol misuse. The study will assist with 
treatment referrals for detox services at Bellevue Hospital Center, but will not otherwise 
directly provide such services or medications. Otherwise any XRB or SLB patient who has 
relapsed and is not interested in continuing their baseline study condition (i.e., an XRB 
participant does not wish to continue injections due to side effects or for any other reason) 
will be encouraged to pursue other appropriate community treatment, the menu of which 
includes the robust addiction service offerings at Bellevue Hospital Center (BHC). BHC's 
services are available to all persons, regardless of insurance status or an ability to pay, and 
include emergency detox inpatient services, methadone treatment, office-based 
buprenorphine, and intensive outpatient and dual diagnosis programs. These services will 
consist of usual care occurring outside of the study and will not be directly provided by or 
paid for by the study. 
6.4.1 Statistical Design 


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This pilot study is exploratory, and Aim 1 is a qualitative estimation of the feasibility and 
acceptability of this new form of buprenorphine in a large urban jail setting.  The study will  
be moderately well-powered using a superiority contrast (A>>B) of XRB vs. SLB 
surrounding Aim 2, retention in treatment post-release. Current rates of successful retention 
in community buprenorphine treatment immediately at one month post-release are 30% or 
lower (6). This current administrative data reflects closely results seen in an original BUP vs. 
methadone NYC jail RCT conducted in 2006-2008 (7). If XRB retention at one month post- 
release (Week 4) is 70% or greater, the study would be powered to detect a significant 
difference between arms. Analysis of treatment retention among XRB vs. SLB will consist of 
simple 2x2 tables for counts and proportions of weeks retained in treatment by arm. We are 
unlikely to extensively model and control for confounders or interaction terms. 
6.4.2 Sample Size Considerations 
A total sample size of N=50 would allow for an estimate of an Odds Ratio of 2.0-3.0 for the 
rate of persons successfully in community buprenorphine treatment at 4 weeks post-release 
(71% vs. 30% success favoring XRB; two-sided alpha of 0.05; 80+% power). The proposed 
sample size will not provide a definitive test of intervention efficacy, but is sized for feasibility 
testing. 
6.4.3 Handling of Missing Data 
Follow-up among individual participants at Bellevue Hospital is encouraged with XOR's 
monetary incentives and tracking protocols. Participants in either arm choosing 
buprenorphine f/u at Bellevue will be particularly likely to complete follow-up. Administrative 
and program data covering community pharmacy fills of buprenorphine products and 
community provider reporting will be used to supplement treatment retention outcomes (Aim 
2). Missing opioid urine toxicology data is considered MissingAsPositive. 


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7 - Trial Administration 
7.1 Ethical Considerations 
Federal Research among Prisoners. See section 5.3.2. 
Emotional Discomfort: There is a small chance that participants may become upset when 
discussing their history of addiction problems, criminal justice involvement, family conflict, 
prior trauma, or role failure, etc. We will discontinue administration of research instruments 
if a subject shows great discomfort or asks to terminate an interview. Such events have not 
been observed in our preliminary studies. 
7.2 Institutional Review Board (IRB) Review 
The protocol, informed consent form(s), recruitment materials, and all participant materials 
will be submitted to the appropriate IRB and institutional research committees for review and 
approval. Approval of both the protocol and the consent form must be obtained before any 
participant is enrolled. Any amendment to the protocol will require review and approval by 
the IRB before the changes are implemented to the study. All changes to the consent form 
will be IRB approved; a determination will be made regarding whether previously consented 
participants need to be re-consented. 
7.3 Subject Confidentiality 
Participants will be asked to provide information regarding a number of sensitive behaviors 
(e.g., alcohol and drug use, sexual history, criminal history and on-going illicit activities). 
This type of personal information divulged by participants at study visits may have adverse 
social and other unknown consequences for participants if released.  Therefore, in addition 
to the safeguards put in place for the collection and storage of all data as described above 
(section 11.0 Data Collection and Management), the study team obtained a Federal 
Certificate of Confidentiality (COC #DA-13-154) to encompass protocol activity and further 
safeguard the possible risk of released confidential information. We will provide all staff with 
training in their responsibilities for maintaining subject confidentiality; we will use unique 
identifiers to identify subjects in the database; all data will be kept in locked filing cabinets or 
on our secure server to which only the investigators and project manager will have access 
to. Study findings will utilize only aggregate data and no publication or presentation will 
involve any use of individual information. 
New York City's H+HC's Human Subject's Research Protections Programs Policies and 
Procedures procedure #26.3 states: 
If a patient is taking part in a Research Project involving a drug, device, or procedure 
(therapeutic trial), the patient's participation must be clearly noted in the patient's electronic 
medical record. Researchers should scan and upload Informed Consent forms into the 
electronic medical record when and where possible, preferably to a research folder. 
Research Records related to an FDA application must be maintained in accordance with 
FDA requirements. 


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Therefore, if you are randomized to XRB: Information about your participation in this study 
will be entered into your Electronic Medical Record (EMR). Once placed in your EMR, the 
information will be available to all of your providers who participate in the EMR system at 
NYC Health + Hospitals including those at Bellevue Medical Records office (HIM). The 
purpose of this entry is to provide research information that has the potential to negatively 
impact your medical care. Bellevue HIM will scan and upload your informed consent to your 
EMR, and are bound by the rules of confidentiality not to reveal your identity to others. 
7.4 Deviations/Unanticipated Problems 
Protocol Deviations: A protocol deviation is any noncompliance with the clinical trial protocol, 
GCP, or Manual of Procedures (MOP) requirements. The noncompliance may be either on 
the part of the participant, the investigator, or the study site staff. As a result of deviations, 
corrective actions are to be developed by the site and implemented promptly. 
These practices are consistent with ICH E6: 
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
• 
5.1 Quality Assurance and Quality Control, section 5.1.1 
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
It is the responsibility of the site PI/study staff to use continuous vigilance to identify and 
report deviations within 30 working days of identification of the protocol deviation, or within 
30working days of the scheduled protocol-required activity. 
Protocol deviations must be reported to the local IRB per their guidelines. The site PI/study 
staff is responsible for knowing and adhering to their IRB requirements. Further details 
about the handling of protocol deviations will be included in the MOP. 
Unanticipated Problems: Incidents or events that meet the OHRP criteria for UPs require the 
creation and completion of an UP report form. It is the site investigator's responsibility to 
report UPs to their IRB and to the DCC/study sponsor. The UP report will include the 
following information: 
• 
Protocol identifying information: protocol title and number, PI's name, and the IRB 
project number; 
• 
A detailed description of the event, incident, experience, or outcome; 
• 
An explanation of the basis for determining that the event, incident, experience, or 
outcome represents an UP; 
• 
A description of any changes to the protocol or other corrective actions that have 
been taken or are proposed in response to the UP. 
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline: 
UPs that are SAEs will be reported to the IRB and to the DCC/study sponsor within 30 days 
of the investigator becoming aware of the event. Any other UP will be reported to the IRB 


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and to the DCC/study sponsor within 30 days of the investigator becoming aware of the 
problem. All UPs should be reported to appropriate institutional officials (as required by an 
institution's written reporting procedures), the supporting agency head (or designee), and 
OHRP within 30 days of the IR's receipt of the report of the problem from the investigator. 
7.5 Data Quality Assurance 
Study clinicians and research staff will undergo the same baseline training at the inception 
of the study. The Program/Project Manager and Data Management staff will ensure the 
quality of the clinicians' and the research assistants' administration of study assessments 
and instruments and of integrity of the data recorded through regular reviews and on-going 
data monitoring. 
7.5.1 Data Collection 
Electronic case report forms (CRFs) will be used to manage the data for this study, and the 
Project Manager will work with study personnel to ensure the completeness and integrity of 
all study data. These electronic CRFs will be taken from the parent XOR U01 NIDA study. 
All data will be checked in real time, stored in a centralized database, reviewed and 
monitored for completeness and accuracy, and undergo a final cleaning following the last 
subject visit, following which the study database will be locked. REDCap will be the data 
entry and database platform for this study. 
Protected Health Information (PHI) will be collected and stored in the form of each 
participant's original signed informed consent and locator form.  These written documents 
will be filed as individual charts and locked securely in a private Department of Population 
Health office cabinet. These charts will be accessed to call and follow-up with patients post- 
release and to maintain the ICF on file. Participants will be assigned sequentially numbered 
unique study ID numbers at the time of consent (e.g. #001-50). These ID numbers will be 
the only identifier entered on Case Report Forms (CRF) and research assessments to 
distinguish one participant from another. Secure laptops will be used for web-based data 
entry, CRF variables will be input into a secure central database on an NYULMC server. 
The laptops themselves will be password-protected, but will not store PHI, study ID number 
information or any research assessment data and will be used for web-based data entry 
only. To maintain a link between the study ID and PHI for purposes of follow-up and record- 
keeping, individual participant charts and research assessment/CRF data there will be a 
master participant ID key that will contain each participant's PHI (name, DOB) and their 
corresponding unique study ID number. This master key identifier file (.xls) will be 
maintained by the PI and Project Manager on a secure NYULMC desktop file and 
accessible only to study staff. 
At the end of a three-year period following study closure, written identifiable data will be 
destroyed. De-identified study data will remain in digital and written file storage for a period 
of 6 years following study conclusion and protocol close per standard NYU IRB guidelines. 
The final de-identifiable digital dataset may be used by the Principal Investigator or Co- 
Investigator for secondary analysis, in which case future IRB-approval would be sought. 
7.5.1.1 Access to Source 


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Source Documents (PHI): 
 
• 
Original signed informed consent and consent form quiz 
• 
Participant locator form 
• 
Randomization Form 
• 
Consent for the release of confidential alcohol or drug treatment information  
• 
Consent for the audio recording of in depth qualitative interviews 
These source documents containing PHI will be filed as individual charts and locked 
securely in a private Department of Population Health office cabinet. These charts will be 
accessed to call and follow-up with patients post-release and to maintain the ICF on file. 
Source Documents (Case Report Forms, De-Identified): 
 
• 
ASILite: Baseline and Follow-up 
• 
Demographics: Baseline 
• 
Pre-arrest recall of drug and alcohol use (Timeline Followback) 
• 
Self-report drug and alcohol use, post-release (Timeline Followback) 
• 
Medication Treatment for Opioid Use Disorder exposure/preference (MOUD 
Preference) 
• 
Treatment Retention Form 
• 
Open-Ended Interview Form 
• 
Qualitative Interview Form 
• 
Medical and Psychiatric History & Laboratory data (pulled from EMR) 
• 
NYS Prescription Monitoring Form 
• 
New Arrests & New Incarceration Form 
• 
Inmate Lookup Form 
• 
Urine Toxicology Report 
• 
Pregnancy Testing 
• 
Adverse Event and Serious Adverse Event reporting 
Participants will be assigned sequentially numbered unique study ID numbers at the time of 
consent (e.g. #001-50). These ID numbers will be the only identifier entered on Case Report 
Forms (CRF) and research assessments to distinguish one participant from another. Secure 
laptops will be used for web-based data entry, CRF variables will be input into a secure 
central database on an NYULMC server. The laptops themselves will be password- 
protected, but will not store PHI, study ID number information or any research assessment 
data and will be used for web-based data entry only.  To maintain a link between the study 
ID and PHI for purposes of follow-up and record-keeping, individual participant charts and 
research assessment/CRF data there will be a master participant ID key that will contain 


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each participant's PHI (name, DOB) and their corresponding unique study ID number. This 
master key identifier file (.xls) will be maintained by the PI and Project Manager on a secure 
NYULMC desktop file and accessible only to study staff. 
7.5.1.2 Data Storage/Security 
Data will be collected on both hard-copy paper CRFs and electronic CRFs. Protected Health 
Information (PHI) will be collected and stored in the form of each participant's original signed 
informed consent, informed consent quiz, randomization form, and locator form. These 
written documents will be filed as individual charts and locked securely in a private 
Department of Population Health office cabinet. These charts will be accessed to call and 
follow-up with patients post-release and to maintain the ICF on file. Participants will be 
assigned sequentially numbered unique study ID numbers at the time of consent (e.g. #001- 
50). These ID numbers will be the only identifier entered on Case Report Forms (CRF) and 
research assessments to distinguish one participant from another. Secure laptops will be 
used for web-based data entry, CRF variables will be input into a secure central database 
on an NYULMC server. The laptops themselves will be password-protected, but will not 
store PHI, study ID number information or any research assessment data and will be used 
for web-based data entry only.  To maintain a link between the study ID and PHI for 
purposes of follow-up and record-keeping, individual participant charts and research 
assessment/CRF data there will be a master participant ID key that will contain each 
participant's PHI (name, DOB) and their corresponding unique study ID number. This  
master key identifier file (.xls) will be maintained by the PI and Project Manager on a secure 
NYULMC desktop file and accessible only to study staff. All hard copy CRFs labeled only 
with ID numbers will be filed in subject files, numbered sequentially. These subject files will 
be kept in a securely locked, private Department of Population Health office cabinet, 
separate from the individual locator charts. 
7.6 Study Records 
Study Records will include: 
• 
All regulatory documents, kept up-to-date in regulatory binders and online Research 
Navigator 
• 
All IRB approved protocol versions 
• 
All IRB approved informed consent forms 
• 
All IRB approved case report forms including surveys 
• 
Individual participant charts 
• 
Original signed ICF & ICF quiz 
• 
Randomization form 
• 
Locator Form 
• 
Medication information 
• 
Subject ID File 
• 
All completed CRFs & surveys, organized by treatment visit. 
7.6.1 Retention of Records 


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At the end of a three-year period following study closure, written identifiable data will be 
destroyed. De-identified study data will remain in digital and written file storage for a period 
of 6 years following study conclusion and protocol close per standard NYU IRB guidelines. 
The final de-identifiable digital dataset may be used by the Principal Investigator or Co- 
Investigator for secondary analysis, in which case future IRB-approval would be sought. 
 
7.7 Study Monitoring 
The PI, Project/Program Manager, and study staff will work to ensure that all information 
collected is accurate and properly protected/secured. The Principal Investigator, Dr. Joshua 
D. Lee, will assume responsibility for monitoring of data collection and of participant safety. 
Any serious or unexpected adverse event will be reported immediately to: 1) the NYC 
DOHMH and NYUSOM-IRBs. 
7.8 Data Safety Monitoring Plan 
A DSMB will monitor this trial. Dr. Rotrosen (NYU Psychiatry) will chair the DSMB. Two 
other board members are to be determined.  The DSMB will conduct ongoing protocol 
review, including data, protocol compliance, safety and efficacy data, in compliance with 
NIDA and NYU IRB guidelines. All board members will meet NIDA requirements regarding 
background and experience, and none will have ethical conflicts, including financial interest 
related to study outcome. Individuals invited to serve on the board will disclose any potential 
conflicts in writing. The board will meet every six months (unless more frequent meetings  
are deemed necessary. Dr. Lee and other research personnel will open each meeting with a 
report on the trial's status, followed by a closed session under the direction of the DSMB 
chairperson, during which time the investigators and research team may be present. This  
will be followed by an executive session restricted to DSMB members. Issues related to 
subject safety, conflict of interest, confidentiality, and ongoing study review (including AEs, 
SAEs, and regulatory issues) will be assessed. Following each DSM Board meeting, 
recommendations will be made to Dr. Lee, and a final report (edited by all Board members) 
will be prepared for reporting to NIDA, the DOHMH and NYU IRBs. The Data Safety 
Monitoring Plan (DSMP) includes stopping rules that specify the outcome differences 
detected between groups during an interim analysis that can result in stopping the pilot trial. 
In general, stopping rules will reflect one of the following conditions: 1) there is clear 
evidence of harm or harmful side-effects of the treatment; 2) there is not likelihood of 
demonstrating treatment benefit; 3) there is overwhelming evidence of the benefit of the 
treatment. However because we are comparing alternative paradigms involving a study 
medication (XRB) or community treatment as usual (SLB) that are already FDA-approved as 
opioid treatment and do not suggest significant safety considerations, early stopping on the 
basis of clear benefit (yes/no) is not anticipated in this trial. 
7.9 Study Modification 
Study modifications, such as the addition of new study personnel, may occur throughout this 
pilot study. All modifications will be submitted to the NYU IRB for review. All IRB approved 
modifications will be stored in regulatory binders. If the IRB determines changes to the 
protocol must be made, the protocol will be edited, submitted for NYU IRB review, and all 
updated versions will then be implemented going forward. 
7.10 Study Discontinuation 


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There is very little chance that this pilot will be discontinued as both investigational 
medications have been FDA approved and have been shown to be safe & effective. 
Additionally, this pilot, proof-of-concept, RCT has been approved by NIDA for the period of 1 
year only. Study termination may be possible in the event of overwhelmingly significant 
efficacy differences between groups or unacceptable adverse events. 
7.11 Study Completion 
The study has an estimated completion date of June 29, 2019. 
7.12 Conflict of Interest Policy 
The independence of this pilot from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be 
disclosed and managed. Furthermore, persons who have a perceived conflict of interest will 
be required to have such conflicts managed in a way that is appropriate to their participation 
in the trial. The study leadership in conjunction with the NYU IRB has established policies 
and procedures for all study group members to disclose all conflicts of interest and will 
establish a mechanism for the management of all reported dualities of interest. 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or 
financial gain greater than the minimum allowable by their institution, etc.) must have the 
conflict reviewed by the NYU Langone Conflict of Interest Management Unit (CIMU) with a 
Committee-sanctioned conflict management plan that has been reviewed and approved by 
the study sponsor prior to participation in this study. All NYULMC investigators will follow the 
applicable conflict of interest policies. 
7.13 Funding Source 
This pilot is supported by a NIDA Administrative Supplement as part of the on-going XOR 
U01 award. 


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Appendices 
 
Appendix 
# 
Name 
Title 
Section 
Topic 
1 
demographics_somatics_xor_nyu_v4.0.pdf 
6 
Methods 
6.2.1 
Efficacy 
2 
addiction_severity_index- 
lite_baseline_8.07.2014.pdf 
6 
Methods 
6.2.1 
Efficacy 
3 
addiction_severity_index- 
lite_drug_history_8.01.2014.pdf 
6 
Methods 
6.2.1 
Efficacy 
4 
addiction_severity_index-lite_follow- 
up_7.25.2014.pdf 
6 
Methods 
6.2.1 
Efficacy 
5 
tlfb_pre-arrest_calendar.pdf 
6 
Methods 
6.2.1 
Efficacy 
6 
tlfb_somatics_xor_nyu_v2_0.pdf 
6 
Methods 
6.2.1 
Efficacy 
7 
urine_toxicology_nyu_xor_v2.0.pdf 
6 
Methods 
6.2.1 
Efficacy 
8 
adverse_event_somatics_xor_nyu_v2.0.pdf 
6 
Methods 
6.2.2.1 AE 
Definition 
and 
Reporting 
9 
sae_xor_nyu_v_1.0.pdf 
6 
Methods 
6.2.2.1 AE 
Definition 
and 
Reporting 


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List of Tables 
 
Title 
Study Visit Schedule 
Study Flowchart 


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References 
1. The National Alliance of Advocates for Buprenorphine Treatment. What exactly is Buprenorphine 
(2018, June 12); Retrieved from: https://www.naabt.org/faq_answers.cfm?ID=2. 
2. Indivior. FDA Approves SUBLOCADETM (Buprenorphine Extended-Release), the First and Only 
Once-Monthly Injectable Buprenorphine Formulation to Treat Moderate to Severe Opioid Use 
Disorder. 2017; 
3. CDC. Drug Overdose Death Data. 2017; 
4. CDC. Wide-ranging online data for epidemiologic research (WONDER). 2017; 
5. Alex B, Weiss DB, Kaba F, Rosner Z, Lee D, Lim S, Venters H, MacDonald R. Death After Jail 
Release. Jan 2017; 23(1):83-87. 
6. Giftos, J. Personal Communication, 2/1/2018. Medical Director, Opioid Treatment Program. 
7. Magura S, Lee JD, Hershberger J, Joseph H, Marsch L, Shropshire C, Rosenblum A. 
Buprenorphine and methadone maintenance in jail and post-release: a randomized clinical trial. Jan 
1, 2009; 99(1-3):222-230. 
8. Lee JD, Grossman E, Truncali A, Rotrosen J, Rosenblum A, Magura S, Gourevitch MN. 
Buprenorphine-naloxone maintenance following release from jail. 2012; 33(1):40-47. 
9. Brinkley-Rubinstein L, Zaller N, Martino S, Cloud DH, McCauley E, Heise A, Seal D. Criminal 
justice continuum for opioid users at risk of overdose. Feb 24, 2018; doi: S0306-4603(18)30089-3.