Clinical trial NCT04716881
Conditions: Opioid-use Disorder
Keywords: naltrexone opioids Opioid Use Disorder
Sponsor: Go Medical Industries Pty Ltd
Start date: 2021-01-25; Completion date: 2022-04-04
Enrollment: 9 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a Phase I, single-center, single arm, open-label study, to establish the pharmacokinetic (PK) parameters of Vivitrol 380 mg IM injection (IP), a US Food and Drug Administration (FDA) approved medication.

Detailed description:
This is a Phase I, single-center, single arm, open-label study, to establish the PK parameters of Vivitrol 380 mg IM injection (IP), a US FDA approved medication. Participants will be healthy volunteers with no significant medical or mental health disorders, who have completed participation in clinical trial GM0017 (i.e. have received the OLANI treatment and have subsequently provided two consecutive plasma levels of naltrexone (NTX) \<0.1ng/mL).

This study will examine the PK profile of Vivitrol IM 380 mg over 6 doses for a treatment period of 196 days. Intense sampling will occur after the 1st and 6th dose of Vivitrol. Participants will be without a DSM 5 - Substance Related Disorders classification. Participants will be required to undergo a Naloxone Challenge Test (NCT) to confirm opiate naivety before administration of the IP. No randomization will occur.

Arms: arm 1: Intramuscular injection of Vivitrol (naltrexone), 380 mg. Six doses given 28 days apart.
Interventions: intervention 1: Naltrexone 380 MG
Intervention descriptions: intervention 1: Vivitrol (naltrexone) 380 mg delivered intramuscularly every 28 days

Protocol documents:
Prot_SAP_000.pdf: 
A PHARMACOKINETIC STUDY OF VIVITROL IN HEALTHY PARTICIPANTS 
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A PHARMACOKINETIC STUDY OF VIVITROL IN 
HEALTHY PARTICIPANTS 
Protocol Identifying Number: GM 0019 
Principal Investigator: Dr. Adam Bisaga 
Sponsor: Go Medical Industries Pty Ltd 
Funded by: Awaiting approval from NIDA 
Version Number: v0.5 
25 March 2021 
NCT04716881


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I. 
TABLE OF CONTENTS 
I. 
TABLE OF CONTENTS ............................................................................................................. ii 
II. 
INDEX OF TABLES AND FIGURES ........................................................................................ vi 
III. 
SPONSOR SIGNATORY: ........................................................................................................ viii 
IV. 
STATEMENT OF COMPLIANCE ............................................................................................. ix 
V. 
PROTOCOL SUMMARY ........................................................................................................... x 
VI. 
SCHEMATIC OF STUDY DESIGN ..........................................................................................XII 
1 
KEY ROLES ............................................................................................................................... 1 
1.1 
SPONSOR ................................................................................................................................. 1 
1.2 
PRINCIPAL INVESTIGATOR .................................................................................................... 1 
1.3 
SITE 1 ........................................................................................................................................ 1 
1.4 
SITE 2 ........................................................................................................................................ 1 
1.5 
CLINICAL LABORATORY ......................................................................................................... 1 
1.6 
CENTRAL CLINICAL LABORATORY ....................................................................................... 1 
1.7 
RESPONSIBLE CLINICIAN ....................................................................................................... 1 
1.8 
MEDICAL MONITOR ................................................................................................................. 1 
1.9 
SPONSOR REPRESENTATIVE ............................................................................................... 2 
1.10 
SITE 1 REPRESENTATIVE ...................................................................................................... 2 
1.11 
SITE 2 REPRESENTATIVE ...................................................................................................... 2 
1.12 
CLINICAL TRIAL CO-ORDINATOR .......................................................................................... 2 
1.13 
CLINICAL PHARMACOLOGIST ................................................................................................ 2 
1.14 
CLINICAL RESEARCH ASSOCIATE ........................................................................................ 2 
2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC ................................... 3 
2.1 
BACKGROUND INFORMATION ............................................................................................... 3 
2.1.1 
Metabolism of Naltrexone ................................................................................................ 3 
2.1.2 
Clinical Use of Naltrexone ................................................................................................ 3 
2.1.3 
Sustained Release Preparations ..................................................................................... 4 
2.1.4 
Investigational Product: Vivitrol IM 380 mg ...................................................................... 4 
2.2 
STUDY RATIONALE ................................................................................................................. 4 
2.3 
POTENTIAL RISKS AND BENEFITS ........................................................................................ 4 
2.3.1 
Known Potential Risks ..................................................................................................... 4 
2.3.2 
Known Potential Benefits ................................................................................................. 8 
3 
OBJECTIVES AND PURPOSE ................................................................................................. 9 
3.1 
PRIMARY OBJECTIVES ........................................................................................................... 9 
3.2 
SECONDARY OBJECTIVES ..................................................................................................... 9 
4 
STUDY DESIGN AND ENDPOINTS ....................................................................................... 10 
4.1 
DESCRIPTION OF THE STUDY DESIGN .............................................................................. 10 
4.2 
STUDY ENDPOINTS ............................................................................................................... 10 
4.2.1 
Primary Endpoint............................................................................................................ 10 
4.2.2 
Secondary Endpoints ..................................................................................................... 10 


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4.2.3 
Primary Efficacy Endpoint: ............................................................................................. 10 
4.2.4 
Secondary Efficacy Endpoints: ...................................................................................... 10 
5 
STUDY ENROLLMENT AND WITHDRAWAL ......................................................................... 11 
5.1 
PARTICIPANT INCLUSION CRITERIA ................................................................................... 11 
5.2 
PARTICIPANT EXCLUSION CRITERIA ................................................................................. 11 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION ........................................................ 12 
5.3.1 
Target Sample Size ....................................................................................................... 12 
5.3.2 
Recruitment .................................................................................................................... 12 
5.3.3 
Retention ........................................................................................................................ 12 
5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION ............................................................... 13 
5.4.1 
Reasons for Withdrawal or Termination ........................................................................ 13 
5.4.2 
Handling of Participant Withdrawals or Termination ...................................................... 13 
5.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY .............................................. 14 
6 
STUDY AGENT ....................................................................................................................... 15 
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION ............................................................. 15 
6.1.1 
Acquisition ...................................................................................................................... 15 
6.1.2 
Formulation, Appearance, Packaging and Labelling ..................................................... 15 
6.1.3 
Product Storage and Stability ........................................................................................ 17 
6.1.4 
Preparation ..................................................................................................................... 17 
6.1.5 
Dosing and Administration ............................................................................................. 17 
6.1.6 
Route of Administration .................................................................................................. 17 
6.1.7 
Dose Adjustments/Modifications/Delays ........................................................................ 17 
6.1.8 
Duration of Therapy ....................................................................................................... 17 
6.1.9 
Tracking of Dose ............................................................................................................ 17 
6.1.10 
Device Specific Considerations ..................................................................................... 18 
6.2 
STUDY AGENT ACCOUNTABILITY PROCEDURES ............................................................ 18 
7 
STUDY PROCEDURES AND SCHEDULE ............................................................................. 19 
7.1 
STUDY PROCEDURES/EVALUATIONS ................................................................................ 19 
7.1.1 
Study Specific Procedures ............................................................................................. 19 
7.2 
LABORATORY PROCEDURES/EVALUATIONS ................................................................... 20 
7.2.1 
Clinical Laboratory Evaluations ...................................................................................... 20 
7.2.2 
Other Assays or Procedures .......................................................................................... 20 
7.2.3 
Total amount of Blood to be collected ........................................................................... 20 
7.2.4 
Specimen Preparation, Handling and Storage .............................................................. 21 
7.2.5 
Specimen Shipment ....................................................................................................... 21 
7.3 
STUDY SCHEDULE ................................................................................................................ 21 
7.3.1 
Screening Visit ............................................................................................................... 21 
7.3.2 
Recruitment .................................................................................................................... 22 
7.3.3 
IP Administration (in-patient care).................................................................................. 22 
7.3.4 
Follow-Up ....................................................................................................................... 23 


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7.3.5 
Final Study Visit ............................................................................................................. 23 
7.3.6 
Early Termination Visit ................................................................................................... 23 
7.3.7 
Unscheduled/Late Visits ................................................................................................ 23 
7.3.8 
AE Follow-up Visit .......................................................................................................... 24 
7.3.9 
Assessment Time Point Table ....................................................................................... 25 
7.4 
CONCOMITANT MEDICATIONS, TREATMENTS AND PROCEDURES .............................. 26 
7.5 
PROHIBITED MEDICATIONS, TREATMENTS AND PROCEDURES ................................... 26 
7.6 
PROPHYLACTIC MEDICATIONS, TREATMENTS AND PROCEDURES ............................. 26 
7.6.1 
Prophylactic Medications ............................................................................................... 26 
7.7 
RESCUE MEDICATIONS, TREATMENTS AND PROCEDURES .......................................... 26 
7.8 
PARTICIPANT ACCESS TO STUDY AGENT AT STUDY CLOSURE ................................... 26 
7.9 
REIMBURSEMENT COSTS .................................................................................................... 26 
8 
ASSESSMENT OF SAFETY ................................................................................................... 27 
8.1 
SPECIFICATION OF SAFETY PARAMETERS ...................................................................... 27 
8.1.1 
Definition of Adverse Events (AE).................................................................................. 27 
8.1.2 
Definition of Serious Adverse Events (SAE) .................................................................. 27 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT ........................................................................ 28 
8.2.1 
Severity of Event ............................................................................................................ 28 
8.2.2 
Relationship to IP ........................................................................................................... 28 
8.2.3 
Expectedness................................................................................................................. 29 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP .......... 30 
8.4 
REPORTING PROCEDURES ................................................................................................. 30 
8.4.1 
Adverse Event Reporting ............................................................................................... 30 
8.4.2 
Serious Adverse Event Reporting .................................................................................. 30 
8.4.3 
Reporting of Pregnancy ................................................................................................. 31 
8.5 
STUDY HALTING RULES ....................................................................................................... 31 
8.5.1 
Study Termination .......................................................................................................... 31 
8.5.2 
On-Site Audits ................................................................................................................ 31 
8.6 
DATA AND SAFETY MONITORING PLAN ADMINISTRATION ............................................. 32 
8.6.1 
Responsibility for data and safety monitoring (DSM) ..................................................... 32 
8.6.2 
Frequency of DSM ......................................................................................................... 32 
8.6.3 
DSMB Plan ..................................................................................................................... 32 
9 
CLINICAL MONITORING ........................................................................................................ 33 
10 
STATISTICAL CONSIDERATIONS ......................................................................................... 34 
10.1 
STATISTICAL AND ANALYTICAL PLANS.............................................................................. 34 
10.2 
STATISTICAL HYPOTHESES ................................................................................................ 34 
10.3 
ANALYSIS DATASETS ........................................................................................................... 34 
10.4 
DESCRIPTION OF STATISTICAL METHODS ....................................................................... 34 
10.4.1 
General Approach .......................................................................................................... 34 
10.4.2 
Analysis of the Primary Endpoint ................................................................................... 34 


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10.4.3 
Analysis of the Secondary Endpoint(s) .......................................................................... 35 
10.4.4 
Safety Analyses ............................................................................................................. 35 
10.4.5 
Adverse Events .............................................................................................................. 35 
10.4.6 
Adherence and Retention Analyses............................................................................... 36 
10.4.7 
Baseline Descriptive Statistics ....................................................................................... 36 
10.4.8 
Planned Interim Analyses .............................................................................................. 36 
10.4.9 
Additional Sub-Group Analyses ..................................................................................... 36 
10.4.10 
Multiple Comparison/ Multiplicity .................................................................................... 36 
10.4.11 
Tabulation of Individual Response Data ........................................................................ 36 
10.4.12 
Exploratory Analyses ..................................................................................................... 36 
10.5 
SAMPLE SIZE ......................................................................................................................... 36 
10.6 
SOFTWARE ............................................................................................................................. 36 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ....................... 37 
12 
QUALITY ASSURANCE AND QUALITY CONTROL .............................................................. 37 
13 
ETHICS/PROTECTION OF HUMAN PARTICIPANTS ........................................................... 37 
13.1 
ETHICAL STANDARD ............................................................................................................. 37 
13.2 
INSTITUTIONAL REVIEW BOARD ......................................................................................... 37 
13.3 
INFORMED CONSENT PROCESS ........................................................................................ 37 
13.3.1 
Consent/Assent and Other Informational Documents Provided to Participants ............ 37 
13.3.2 
Consent Procedures and Documentation ...................................................................... 37 
13.4 
PARTICIPANT AND DATA CONFIDENTIALITY ..................................................................... 38 
13.4.1 
Research Use of Stored Human Samples, Specimens or Data .................................... 38 
13.5 
FUTURE USE OF STORED SPECIMENS.............................................................................. 38 
14 
DATA HANDLING AND RECORD KEEPING ......................................................................... 39 
14.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES.......................................... 39 
14.2 
STUDY RECORDS RETENTION ............................................................................................ 39 
14.3 
PROTOCOL DEVIATIONS ...................................................................................................... 39 
14.4 
PUBLICATION AND DATA SHARING POLICY ...................................................................... 40 
15 
STUDY ADMINISTRATION ..................................................................................................... 40 
15.1 
STUDY LEADERSHIP ............................................................................................................. 40 
16 
CONFLICT OF INTEREST POLICY ........................................................................................ 40 
17 
REVISION HISTORY ............................................................................................................... 41 
18 
SUMMARY OF CHANGES FROM PREVIOUS VERSION ..................................................... 42 
18.1 
Version 0.2 ............................................................................................................................... 42 
18.2 
Version 0.3 ............................................................................................................................... 42 
18.3 
Version 0.4 ............................................................................................................................... 42 
18.4 
Version 0.5 ............................................................................................................................... 44 
19 
LITERATURE REFERENCES ................................................................................................. 46 
 
 
 


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II. 
INDEX OF TABLES AND FIGURES 
Table 7-1: Assessment Time Points ......................................................................................... 25 
 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Term or Abbreviation 
Description 
6βN
6-β-naltrexol
ADR
Adverse Drug Reaction
AE
Adverse Event
AUC
Area Under the Curve
CRF
Case Report Form
CRO
Contract Research Organization
CSSRS
Columbia Suicide Severity Rating Scale
DSMB
Data Safety Monitoring Board
eCRF
Electronic Case Report Forms
EUC 
Electrolytes, Urea, Creatinine 
FBE 
Full Blood Examination 
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GHQ 
General Health Questionnaire 
GLP
Good Laboratory Practices
GMP
Good Manufacturing Practices
HCV 
Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
HREC 
Human Research Ethics Committee 
IB 
Investigator’s Brochure 
ICH
International Council for Harmonization
IP
Investigational Product
IRB 
Institutional Review Board 
LFT 
Liver Function Tests 
MHA 
Mental Health Assessment 
NCT
Naloxone Challenge Test
NTX 
Naltrexone 
NYSPI 
New York State Psychiatric Institute 
OLANI 
O’Neil Long Acting Naltrexone Implant 
PI 
Principal Investigator 
PIC 
Participant Information Consent 
PK 
Pharmacokinetic 
QC
Quality Control


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Term or Abbreviation 
Description 
SAE
Serious Adverse Event
SOP
Standard Operating Procedure
UDS
Urine Drug Screen
 
 
 






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V. 
PROTOCOL SUMMARY 
Title: 
A PHARMACOKINETIC STUDY OF VIVITROL IN 
HEALTHY PARTICIPANTS 
Overview: 
This is a Phase I, single-center, single arm, open-label study, to 
establish the pharmacokinetic (PK) parameters of Vivitrol 380 mg 
IM injection (IP), a US Food and Drug Administration (FDA) 
approved medication. Participants will be healthy volunteers with no 
significant medical or mental health disorders, who have completed 
participation in clinical trial GM 0017 (i.e. have received the 
OLANI treatment and have subsequently provided two consecutive 
plasma levels of naltrexone (NTX) <0.1ng/mL).  
This study will examine the PK profile of Vivitrol IM 380 mg over 
6 doses for a treatment period of 196 days. Intense sampling will 
occur after the 1st and 6th dose of Vivitrol. Participants will be 
without a DSM 5 - Substance Related Disorders classification. 
Participants will be required to undergo a Naloxone Challenge Test 
(NCT) to confirm opiate naivety before administration of the IP. No 
randomization will occur. 
Note: In the future, an expansion of this protocol is planned in order 
to include additional participants that initially receive 2 doses of 
Vivitrol followed by the OLANI treatment (i.e. the ‘cross-over’ 
group). This expansion may occur under this same protocol ID or a 
new protocol ID. 
Objectives: 
Primary: 
 
 
 To determine the PK parameters of Cmax, Tmax, Ctrough 
(Day 28), and AUC for the 1st and 6th dose of Vivitrol 
IM 380mg. 
Secondary:  
 To determine steady state characteristics and demonstrate no 
accumulation between repeat doses. 
 To establish the safety and tolerability of the NTX injection over 
6 months.  
Endpoint: 
Primary: 
 PK parameters, including Cmax, Ctrough (Day 28), and AUC 
Secondary: 
 To demonstrate no accumulation following repeat doses of 
Vivitrol IM 380 mg. 
Safety endpoints will be captured through 6 months and will 
include the incidence of adverse events (AEs) including:  
 deaths 
 serious adverse events (SAEs) 
 AEs leading to discontinuation 
 common AEs


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 AEs of special interest (injection site reactions and 
hepatic effects) 
 laboratory abnormalities (absolute values and 
changes over time in laboratory parameters) 
 the proportion of participants who discontinue 
treatment due to AEs)
Population: 
Up to 6 healthy participants to be recruited (with 4 required to 
complete the study), aged at least 18 (≥18) and no older than 57 
(<58), without a DSM 5 - Substance Related Disorders 
classification, residing within the New York metropolitan area. 
Participants are to be recruited with the perquisite of having 
successfully finished study GM 0017. 
Phase: 
I 
Number of 
Sites: 
Two  
Site 1: New York State Psychiatric Institute, 1051 Riverside Drive, 
New York, NY 10032, USA (administration center for PI) 
Site 2: Clinilabs, 423 West 55th St, New York, 10019 (Vivitrol 
reference dose administration and follow-up visits) 
Investigational 
Product: 
The investigational product (IP) (intended reference product) is a 
Vivitrol Intramuscular injection, 380 mg (six doses given 28 days 
apart) 
Study 
Duration: 
Estimated 9 months 
Participant 
Duration: 
196 days  
 
 




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1 
KEY ROLES 
1.1 
SPONSOR 
Go Medical Industries Pty Ltd,  
200 Churchill Ave, Subiaco, Perth, WA 6008, Australia 
 
 
1.2 
PRINCIPAL INVESTIGATOR 
Adam Bisaga M.D. 
New York State Psychiatric Institute, 1051 Riverside Dr., New York, NY 10032 
 
1.3 
SITE 1 
New York State Psychiatric Institute, 1051 Riverside Dr., Unit 120, New York, NY 10032 
(Administrative center) 
 
1.4 
SITE 2 
Clinilabs, 423 West 55th St, New York, 10019  
(IP administration and follow-up) 
 
1.5 
CLINICAL LABORATORY 
(NALTREXONE AND 6-β-NALTREXOL BLOOD ANALYSIS ONLY) 
WuXi AppTec , XenoBiotic Laboratories, Inc. 
107 Morgan Lane, Plainsboro, NJ, 08536 
Tel: 609-606-6620; Fax: 609-799-7497 
 
1.6 
CENTRAL CLINICAL LABORATORY 
(LFT, FBC, EUC, URINE DRUG SCREEN AND ROUTINE PATHOLOGY) 
Laboratory Corporation of America 
 
1.7 
RESPONSIBLE CLINICIAN 
Adam Bisaga M.D. 
New York State Psychiatric Institute, 1051 Riverside Dr., New York, NY 10032 
 
1.8 
MEDICAL MONITOR  
Dr. Jon Ruckle, Pacific Pharma Group, LLC, 1402 S. Brookside Terrace, Tacoma, WA. 
98465-1220 
 
 


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1.9 
SPONSOR REPRESENTATIVE 
Mr. Chin-Tark Chan BSc (IT) BEng (Mech) Hons 
Operations Manager, Pharmaceutical Division 
Go Medical Industries Pty Ltd 
 
1.10 SITE 1 REPRESENTATIVE 
Adam Bisaga M.D. 
New York State Psychiatric Institute, 1051 Riverside Dr., Unit 120, New York, NY 10032 
 
1.11 SITE 2 REPRESENTATIVE 
Dr. Maha Ahmad 
Provided by Clinilabs, 423 West 55th St, New York, 10019 
 
1.12 CLINICAL TRIAL CO-ORDINATOR 
Patricia Mensa. New York State Psychiatric Institute, 1051 Riverside Dr., New York, NY 
10032  
 
1.13 CLINICAL PHARMACOLOGIST 
Dr. Serge Cremers, Pathology & Cell Biology, Department of Medicine and Irving Institute 
for Clinical and Translational Research, Columbia University Irving Medical Center, 622 
West 168 Street, New York, NY 
 
1.14 CLINICAL RESEARCH ASSOCIATE 
Provided by Clinilabs, 423 West 55th St, New York, 10019 
 


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2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC  
2.1 
BACKGROUND INFORMATION 
NTX is a synthetic derivative of thebaine, a minor constituent of opium. It is a nonspecific 
pure opioid antagonist. NTX binds competitively to all classes of opioid receptors with the 
following order of preference µ>κ>δ, with a high affinity for the µ-opioid receptor. It blocks 
the effects of opioids by competitive binding at opioid receptors. NTX is approved by the 
FDA for the treatment of opioid dependence/opioid use disorder (OUD) and is also approved 
for the treatment of alcohol use disorder. NTX is currently registered in USA as a once daily 
oral formulation containing 50 mg of NTX and as a once-monthly injectable formulation 
containing 380 mg of NTX (Vivitrol).  
2.1.1 
Metabolism of Naltrexone  
NTX is well absorbed orally (96%), but it undergoes a significant first pass metabolism 
resulting in only 5 to 40% oral bioavailability. NTX is extensively metabolized in humans1. 
Production of the primary metabolite, 6β-naltrexol (6βN), is mediated by dihydrodiol 
dehydrogenase, a cytosolic family of enzymes. Two other minor metabolites are 2-hydroxy-
3-methoxy-6β-naltrexol and 2-hydroxy-3-methoxy-naltrexone2. NTX and 6-BN terminal 
half-life values have been reported as ranging from 2 to 10 hours for NTX3–5 and 7.5 to 13 
hours for 6-BN3,5,6. Both NTX and 6-BN are excreted primarily by the kidneys. There is a 
large amount of variation in the metabolism and PK of NTX. In one study, the enzyme 
kinetics of the formation of 6-BN from NTX using human liver cytosol preparation showed a 
2.9 fold variability in Vmax, a 3.2 fold variability in Km and a 7.7 fold variability in intrinsic 
clearance7. The systemic clearance of NTX supersedes the hepatic blood flow, suggesting the 
NTX is highly extracted and extra hepatic sites of drug metabolism exist. 
2.1.2 
Clinical Use of Naltrexone  
While NTX is a potent antagonist and efficiently blocks the effects of exogenous opioids 
such as heroin, the success of NTX for the treatment of opioid dependence has been limited 
by poor patient compliance with the oral formulation8. Unlike alternative pharmacotherapies 
for opioid dependence such as methadone and buprenorphine, NTX has no positive 
reinforcing effects, ceasing NTX has no withdrawal or negative consequences. Thus, there is 
little incentive to continue taking the oral formation, with patients often stopping the 
medication and returning to opioid use. After opioid detoxification, patients are likely to have 
reduced tolerance to opioids. As the blockade of exogenous opioids provided by NTX wanes 
and eventually dissipates completely, patients who have been treated with NTX may respond 
to lower doses of opioids than previously used, just as they would shortly after completing 
detoxification. This could result in potentially life-threatening opioid intoxication (respiratory 
compromise or arrest, circulatory collapse, etc.) if the patient uses previously tolerated doses 
of opioids9. 
Better NTX compliance has been observed when a responsible adult is available to supervise 
daily NTX dosing10. It has been reported that the method of daily oral NTX treatment is not 
an effective long term treatment in most patients11,12. Clinical data has indicated that poor 
medication compliance occurs with daily oral NTX maintenance treatment for opioid 
dependence8,10,13. It has been proposed that the development of a sustained release NTX 
preparation would combat these issues and lead to improved outcomes for opioid users. 


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2.1.3 
Sustained Release Preparations 
Wise (1984) developed a NTX (70%)-poly(D,L-lactide-co-glycolide) copolymer (30%) 
implant14, which was the first biodegradable drug delivery system approved by the FDA for 
clinical testing, but was limited by “burst release” in human trials. Previous findings also 
suggested that polymeric NTX sustained release systems are biocompatible formulations15,16. 
Additionally, several dosage forms have also been proposed. For example, a NTX-poly(lactic 
acid) composite17, which had an effective blocking action to morphine in rats for 24 days; 
NTX-copolymer (90% L-lactic acid and 10% glycolic acid) beads18,which would provide 
constant NTX levels for one month, and a NTX pamoate linear poly(ortho esters) disk19, 
which released NTX pamoate for 21 days. 
2.1.4 
Investigational Product: Vivitrol IM 380 mg 
In 2006, a 30 day NTX intramuscular injection known as Vivitrol (Alkermes) was approved 
by the FDA for the treatment of alcohol dependence, and it was also approved in 2010 for the 
treatment of opioid dependence20,21. Vivitrol consists of a NTX PLGA microsphere 
suspension delivered intramuscularly via an injection. Some studies revealed that a 380 mg 
injection can produce a mean trough naltrexone blood level above 1.33 ng/ml for 
approximately four weeks22.  
Vivitrol PK will be captured in the present study to be used as a reference product in 
 
drug application for the OLANI product which is being developed under 
 
 
2.2 
STUDY RATIONALE 
This is a Phase I, single-center, single arm, open-label study to determine PK parameters for 
Vivitrol 380 mg IM which is an FDA approved formulation. The PK characteristics of 
Vivitrol can then be used as the approved comparator product in a 
 application for 
OLANI. 
Participants will be healthy volunteers with no opioid or other substance use disorders and no 
other significant medical or mental health disorders. It should be noted that participants from 
Clinical Trial GM 0017 have already received the OLANI treatment and have subsequently 
provided two consecutive plasma levels of NTX <0.1 ng/mL. Only these participants shall be 
offered recruitment into the study to allow for the inter-individual comparison of Vivitrol and 
OLANI PK parameters. 
Note: In the future, an expansion of this protocol is planned in order to include additional 
participants that initially receive 2 doses of Vivitrol followed by the OLANI treatment (i.e. 
the ‘cross-over’ group). This expansion may occur under this same protocol ID or a new 
protocol ID. 
2.3 
POTENTIAL RISKS AND BENEFITS 
2.3.1 
Known Potential Risks 
The following sections (1-11) are taken from Section 5 of the Vivitrol US Prescribing 
Information23 which should be consulted for detailed information. 
1. 
Vulnerability to Opioid Overdose 
After opioid detoxification, patients are likely to have reduced tolerance to opioids. 
VIVITROL blocks the effects of exogenous opioids for approximately 28 days after 


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administration. However, as the blockade wanes and eventually dissipates completely, 
patients who have been treated with VIVITROL may respond to lower doses of opioids than 
previously used, just as they would have shortly after completing detoxification. This could 
result in potentially life-threatening opioid intoxication (respiratory compromise or arrest, 
circulatory collapse, etc.) if the patient uses previously tolerated doses of opioids. Cases of 
opioid overdose with fatal outcomes have been reported in patients who used opioids at the 
end of a dosing interval, after missing a scheduled dose, or after discontinuing treatment.  
Patients should be alerted that they may be more sensitive to opioids, even at lower doses, 
after VIVITROL treatment is discontinued, especially at the end of a dosing interval (i.e., 
near the end of the month that VIVITROL was administered), or after a dose of VIVITROL 
is missed. It is important that patients inform family members and the people closest to the 
patient of this increased sensitivity to opioids and the risk of overdose.  
There is also the possibility that a patient who is treated with VIVITROL could overcome the 
opioid blockade effect of VIVITROL. Although VIVITROL is a potent antagonist with a 
prolonged pharmacological effect, the blockade produced by VIVITROL is surmountable. 
The plasma concentration of exogenous opioids attained immediately following their acute 
administration may be sufficient to overcome the competitive receptor blockade. This poses a 
potential risk to individuals who attempt, on their own, to overcome the blockade by 
administering large amounts of exogenous opioids. Any attempt by a patient to overcome the 
antagonism by taking opioids is especially dangerous and may lead to life-threatening opioid 
intoxication or fatal overdose. Patients should be told of the serious consequences of trying to 
overcome the opioid blockade. 
2. 
Injection Site Reactions  
VIVITROL must be prepared and administered by a healthcare provider. VIVITROL 
injections may be followed by pain, tenderness, induration, swelling, erythema, bruising, or 
pruritus; however, in some cases injection site reactions may be very severe. In the clinical 
trials, one patient developed an area of induration that continued to enlarge after 4 weeks, 
with subsequent development of necrotic tissue that required surgical excision. In the 
postmarketing period, additional cases of injection site reaction with features including 
induration, cellulitis, hematoma, abscess, sterile abscess, and necrosis, have been reported. 
Some cases required surgical intervention, including debridement of necrotic tissue. Some 
cases resulted in significant scarring. The reported cases occurred primarily in female 
patients.  
VIVITROL is administered as an intramuscular gluteal injection, and inadvertent 
subcutaneous injection of VIVITROL may increase the likelihood of severe injection site 
reactions. The needles provided in the carton are customized needles. VIVITROL must not 
be injected using any other needle. The needle lengths (either 1 1/2 or 2 inches) may not be 
adequate in every patient because of body habitus. Body habitus should be assessed prior to 
each injection for each patient to assure that the proper needle is selected and that the needle 
length is adequate for intramuscular administration. For patients with a larger amount of 
subcutaneous tissue overlying the gluteal muscle, the administering healthcare provider may 
utilize the supplied 2-inch needle with needle protection device to help ensure that the 
injectate reaches the intramuscular mass. For very lean patients, the 1 1/2-inch needle may be 
appropriate to prevent the needle contacting the periosteum. Either needle may be used for 
patients with average body habitus. Healthcare providers should ensure that the VIVITROL 
injection is given correctly, and should consider alternate treatment for those patients whose 
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Patients should be informed that any concerning injection site reactions should be brought to 
the attention of the healthcare provider. Patients exhibiting signs of abscess, cellulitis, 
necrosis, or extensive swelling should be evaluated by a physician to determine if referral to a 
surgeon is warranted. 
3. 
Precipitation of Opioid Withdrawal 
The symptoms of spontaneous opioid withdrawal (which are associated with the 
discontinuation of opioid in a dependent individual) are uncomfortable, but they are not 
generally believed to be severe or necessitate hospitalization. However, when withdrawal is 
precipitated abruptly by the administration of an opioid antagonist to an opioid-dependent 
patient, the resulting withdrawal syndrome can be severe enough to require hospitalization. 
Review of postmarketing cases of precipitated opioid withdrawal in association with 
naltrexone treatment has identified cases with symptoms of withdrawal severe enough to 
require hospital admission, and in some cases, management in the intensive care unit.  
To prevent occurrence of precipitated withdrawal in patients dependent on opioids, or 
exacerbation of a pre-existing subclinical withdrawal syndrome, opioid-dependent patients, 
including those being treated for alcohol dependence, should be opioid-free (including 
tramadol) before starting VIVITROL treatment. An opioid-free interval of a minimum of 7–
10 days is recommended for patients previously dependent on short-acting opioids. Patients 
transitioning from buprenorphine or methadone may be vulnerable to precipitation of 
withdrawal symptoms for as long as two weeks.  
If a more rapid transition from agonist to antagonist therapy is deemed necessary and 
appropriate by the healthcare provider, monitor the patient closely in an appropriate medical 
setting where precipitated withdrawal can be managed.  
In every case, healthcare providers should always be prepared to manage withdrawal 
symptomatically with non-opioid medications because there is no completely reliable method 
for determining whether a patient has had an adequate opioid-free period. A naloxone 
challenge test may be helpful; however, a few case reports have indicated that patients may 
experience precipitated withdrawal despite having a negative urine toxicology screen or 
tolerating a naloxone challenge test (usually in the setting of transitioning from 
buprenorphine treatment). Patients should be made aware of the risks associated with 
precipitated withdrawal and encouraged to give an accurate account of last opioid use. 
Patients treated for alcohol dependence with VIVITROL should also be assessed for 
underlying opioid dependence and for any recent use of opioids prior to initiation of 
treatment with VIVITROL. Precipitated opioid withdrawal has been observed in alcohol-
dependent patients in circumstances where the prescriber had been unaware of the additional 
use of opioids or co-dependence on opioids. 
4. 
Hepatoxicity 
Cases of hepatitis and clinically significant liver dysfunction were observed in association 
with VIVITROL exposure during the clinical development program and in the postmarketing 
period. Transient, asymptomatic hepatic transaminase elevations were also observed in the 
clinical trials and postmarketing period. Although patients with clinically significant liver 
disease were not systematically studied, clinical trials did include patients with asymptomatic 
viral hepatitis infections. When patients presented with elevated transaminases, there were 
often other potential causative or contributory etiologies identified, including pre-existing 
alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other 
potentially hepatotoxic drugs. Although clinically significant liver dysfunction is not 


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typically recognized as a manifestation of opioid withdrawal, opioid withdrawal that is 
precipitated abruptly may lead to systemic sequelae including acute liver injury.  
Patients should be warned of the risk of hepatic injury and advised to seek medical attention 
if they experience symptoms of acute hepatitis. Use of VIVITROL should be discontinued in 
the event of symptoms and/or signs of acute hepatitis.  
5. 
Depression and Suicidality 
Alcohol- and opioid-dependent patients, including those taking VIVITROL, should be 
monitored for the development of depression or suicidal thinking. Families and caregivers of 
patients being treated with VIVITROL should be alerted to the need to monitor patients for 
the emergence of symptoms of depression or suicidality, and to report such symptoms to the 
patient’s healthcare provider.  
Alcohol Dependence  
In controlled clinical trials of VIVITROL administered to adults with alcohol dependence, 
adverse events of a suicidal nature (suicidal ideation, suicide attempts, completed suicides) 
were infrequent overall, but were more common in patients treated with VIVITROL than in 
patients treated with placebo (1% vs 0%). In some cases, the suicidal thoughts or behavior 
occurred after study discontinuation, but were in the context of an episode of depression that 
began while the patient was on study drug. Two completed suicides occurred, both involving 
patients treated with VIVITROL.  
Depression-related events associated with premature discontinuation of study drug were also 
more common in patients treated with VIVITROL (~1%) than in placebo-treated patients 
(0%).  
In the 24-week, placebo-controlled pivotal trial in 624 alcohol-dependent patients, adverse 
events involving depressed mood were reported by 10% of patients treated with VIVITROL 
380 mg, as compared to 5% of patients treated with placebo injections.  
Opioid Dependence  
In an open-label, long-term safety study conducted in the US, adverse events of a suicidal 
nature (depressed mood, suicidal ideation, suicide attempt) were reported by 5% of opioid-
dependent patients treated with VIVITROL 380 mg (n=101) and 10% of opioid-dependent 
patients treated with oral naltrexone (n=20). In the 24-week, placebo-controlled pivotal trial 
that was conducted in Russia in 250 opioid-dependent patients, adverse events involving 
depressed mood or suicidal thinking were not reported by any patient in either treatment 
group (VIVITROL 380 mg or placebo).  
6. 
When Reversal of VIVITROL Blockade Is Required for Pain Management 
In an emergency situation in patients receiving VIVITROL, suggestions for pain management 
include regional analgesia or use of non-opioid analgesics. If opioid therapy is required as 
part of anesthesia or analgesia, patients should be continuously monitored in an anesthesia 
care setting by persons not involved in the conduct of the surgical or diagnostic procedure. 
The opioid therapy must be provided by individuals specifically trained in the use of 
anesthetic drugs and the management of the respiratory effects of potent opioids, specifically 
the establishment and maintenance of a patent airway and assisted ventilation.  
Irrespective of the drug chosen to reverse VIVITROL blockade, the patient should be 
monitored closely by appropriately trained personnel in a setting equipped and staffed for 
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7. 
Eosinophilic Pneumonia 
In clinical trials with VIVITROL, there was one diagnosed case and one suspected case of 
eosinophilic pneumonia. Both cases required hospitalization, and resolved after treatment 
with antibiotics and corticosteroids. Similar cases have been reported in postmarketing use. 
Should a person receiving VIVITROL develop progressive dyspnea and hypoxemia, the 
diagnosis of eosinophilic pneumonia should be considered. Patients should be warned of the 
risk of eosinophilic pneumonia, and advised to seek medical attention should they develop 
symptoms of pneumonia. Clinicians should consider the possibility of eosinophilic 
pneumonia in patients who do not respond to antibiotics.  
8. 
Hypersensitivity Reactions Including Anaphylaxis 
Cases of urticaria, angioedema, and anaphylaxis have been observed with use of VIVITROL 
in the clinical trial setting and in postmarketing use. Patients should be warned of the risk of 
hypersensitivity reactions, including anaphylaxis. In the event of a hypersensitivity reaction, 
patients should be advised to seek immediate medical attention in a healthcare setting 
prepared to treat anaphylaxis. The patient should not receive any further treatment with 
VIVITROL.  
9. 
Intramuscular Injections 
As with any intramuscular injection, VIVITROL should be administered with caution to 
patients with thrombocytopenia or any coagulation disorder (e.g., hemophilia and severe 
hepatic failure).  
10. 
Alcohol Withdrawal 
Use of VIVITROL does not eliminate nor diminish alcohol withdrawal symptoms.  
11. 
Interference with Laboratory Tests 
VIVITROL may be cross-reactive with certain immunoassay methods for the detection of 
drugs of abuse (specifically opioids) in urine. For further information, reference to the 
specific immunoassay instructions is recommended.  
12. 
Known side-effects from NTX include difficulty sleeping, anxiety, nervousness, 
abdominal pain/cramps, nausea and/or vomiting, low energy, join and muscle pain, 
headache, loss of appetite, diarrhea, constipation, increased thirst, increased energy, 
depressive mood, irritability, dizziness, skin rash, delayed ejaculation, erection 
dysfunction, reduced sexual desire, and chills. 
13. 
Naloxone injection may cause withdrawal symptoms in individuals who are opioid 
dependent including nausea, vomiting, diarrhea, stomach pain, fever, sweating, body 
aches, weakness, running nose, goosebumps, shivering, increased heart rate, and 
anxiety. 
2.3.2 
Known Potential Benefits 
1. 
There are no known potential benefits of this treatment in the study cohort.  
2. 
There is a large potential benefit to the opiate addicted community as robust PK data 
will allow for the ongoing development of the OLANI product.  
 
 


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3 
OBJECTIVES AND PURPOSE 
3.1 
PRIMARY OBJECTIVES 
To determine the PK parameters of Cmax, Tmax and AUC for the 1st and 6th dose of 
Vivitrol IM 380 mg, and Ctrough for the 1st through 6th dose. Ctrough is defined as the 
naltrexone level obtained 28 days after each dose. PK parameters will be collected 
over a treatment period of 196 days. 
Primary outcomes used to determine these properties will be based on results from plasma 
concentration of NTX and 6βN as ascertained from blood samples taken at the following time 
points:  
 Day 0 (predose, +1, 2, 4, 8, 12 & 24 hours), 1.5, 1.75, 2, 3, 5, 7, 10, 14, 17, 21, 24, 
28,  
 Day 56, 84, 112 days,  
 Day 140 (predose +1, 2, 4, 8 & 12 hours), 141, 141.5, 141.75, 142, 143, 145, 147, 
150, 154, 157, 161, 164, 168, 182, and 196 days 
3.2 
SECONDARY OBJECTIVES 
 To confirm no accumulation between repeat doses 
 To determine the safety and tolerability of Vivitrol over 196 days. 
Safety endpoints will be captured throughout and will include the incidence of AEs 
including: 
 deaths 
 SAEs 
 AEs leading to discontinuation 
 common AEs 
 AEs of special interest (injection site reactions and hepatic effects) 
 laboratory abnormalities (absolute values and changes over time in laboratory 
parameters) 
 the proportion of participants who discontinue treatment due to AEs) 
 
 


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4 
STUDY DESIGN AND ENDPOINTS 
4.1 
DESCRIPTION OF THE STUDY DESIGN 
Participants who have completed the study end points of GM 0017 (i.e. two consecutive 
monthly plasma results <0.1 ng/mL for NTX) will be offered enrolment into the study. 
Up to 15 participants will be recruited onto this arm with 12 expected to complete to full 
dosing and sampling schedule. 
Participants will receive a 380 mg Vivitrol IM injection and blood samples will be taken 
according to the sampling schedule of Table 7-1. Subsequently, participants will be re-
administered Vivitrol injections every 28 days for a total of 6 Vivitrol injections. Blood 
sampling will be performed as per Table 7-1. The administration of 6 repeated Vivitrol 
injections is to confirm the published findings that no accumulation of Vivitrol is evident 
after repeated injections and to allow a direct time frame comparison to future 
bioequivalence study with OLANI.  
This PK information, including day 28 naltrexone trough level, is needed so that Vivitrol 
can be used as the reference product for previous and future studies of OLANI. 
4.2 
STUDY ENDPOINTS 
4.2.1 
Primary Endpoint 
 The collection of at least 75% of the PK blood samples including respective day 28 blood 
collections for 1st and 6th injection phase.  
4.2.2 
Secondary Endpoints 
Safety endpoints will be captured through 6 months and will include the incidence of AEs 
including: 
o deaths 
o SAEs 
o AEs leading to discontinuation 
o common AEs 
o AEs of special interest (injection site reactions and hepatic effects) 
o laboratory abnormalities (absolute values and changes over time in laboratory 
parameters   
o the proportion of participants who discontinue treatment due to AEs 
4.2.3 
Primary Efficacy Endpoint: 
 Establishment of reference product Vivitrol 28-day naltrexone trough blood level.  
 Mean Cmax, Tmax, AUC, Ctrough for NTX blood level 
 Mean Cmax, Tmax, AUC, Ctrough for 6βN blood level 
4.2.4 
Secondary Efficacy Endpoints: 
 Frequency of AEs and SAEs  
 


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5 
STUDY ENROLLMENT AND WITHDRAWAL 
5.1 
PARTICIPANT INCLUSION CRITERIA 
Healthy participants without a DSM 5 - Substance Related Disorders classification will be 
recruited for this study. Participants will be assessed for their general health and mental 
health status. 
Participants will be required to undergo a NCT to confirm opiate naivety before 
administration of the IP.  
To qualify for the study participation, participants have to: 
 Have completed GM 0017 (i.e. been administered OLANI (3.6 gram) and 
provided two consecutive monthly blood samples of NTX below 0.1 ng/mL) 
 Men or women aged at least 18 (≥18) and no older than 57 (<58), without DSM 5 
- Substance Related Disorders classification; in sustained remission is not 
exclusionary 
 Able and willing to comply with the requirements of the protocol 
 Able and willing to provide written informed consent 
 Willing to undergo an injection of NTX to allow for investigational drug 
administration in the intramuscular tissue 
 Have an initial weight between 45.3 and 81.6 kilograms (inclusive) or have a 
BMI inclusive of 18.5 to 30.0. 
5.2 
PARTICIPANT EXCLUSION CRITERIA 
Participants will not be eligible for the study if they meet any of the following criteria: 
 Is currently on active NTX medication. 
 Positive UDS at screening for illicit substances. 
 Has a condition which requires treatment with opioid based medication. 
 Has a known hypersensitivity to NTX. 
 Is prone to skin rashes, irritation or has a skin condition such as recurrent eczema 
that is likely to impact the injection site area, or as determined by the evaluating 
physician. 
 Demonstrates any abnormal skin tissue in the proposed injection area. 
 Is pregnant or planning to be. Women need to have negative pregnancy test at 
screening. Women need to agree to practice an effective method of contraception 
throughout participation. 
 Participant is breastfeeding or planning to be. 
 Has a current significant neurological (including cognitive and psychiatric disorders), 
 Any clinically important abnormal finding as determined by medical history, 
physical examination, ECG or clinical laboratory tests. 
 Any additional condition(s) that in the investigator’s opinion would prohibit 
the participant from completing the study or would not be in the best interest 


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of the participant. 
 ALT or AST >3 times the upper end of the laboratory normal range. 
 Any methadone use 14 days prior to screening, and up to Study Day 0. 
 Current DSM 5 diagnosis of schizophrenia, bipolar, anxiety, or depressive disorder, 
confirmed by MINI assessment, or currently treated with medications for anxiety or 
depression. Past history (in remission DSM 5 classification) of anxiety or 
depression is not exclusionary. 
 Any elevated risk for suicide measured using the Columbia Suicide Severity 
Rating Scale, endorsing any of the items in the past month (C-SSRS, Lifetime) 
 Is participating or intending to participate in any other clinical trial during the duration 
of this study. 
 Is allergic to any of the ingredients in Vivitrol or the diluent used to mix Vivitrol (i.e. 
carboxymethylcellulose sodium, polysorbate 20, sodium chloride, sodium hydroxide 
and hydrochloric acid as pH adjusters, in water for injection). 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION 
5.3.1 
Target Sample Size 
Recruitment into the study will be solely offered to the 19 participants who have completed 
the previous study GM 0017. Up to 15 participants from GM 0017 will be targeted for 
recruitment to this study. We expect that 12 of the 15 participants will complete the study 
(80%), which is providing at least 75% valid PK blood samples including Day 28 and Day 
168 Vivitrol trough levels. 
5.3.2 
Recruitment 
All participants will be seen by a study clinician (MD or PA) for a screening evaluation and 
mental status examination as part of routine admission procedures at Clinilabs. Final 
informed consent for the study will be obtained after full medical workup is complete. The 
research staff knows the protocol well, and is able to explain study to the participant. 
Procedures for training study clinicians in the protocol and consent form include initial 
presentations by the Principal Investigator (PI) at weekly staff meetings, and weekly 
discussion of inclusion/exclusion criteria and study eligibility for each screening participant. 
Study participation will only be offered to those that have successfully completed GM 0017 
and therefore no advertising for recruitment outside of GM 0017 participants is required.  
5.3.3 
Retention 
All participants will be reimbursed as per section 7.9 for each clinic visit to compensate them 
for the time spent doing research assessments as well as the cost of transportation. We will 
maintain a close phone contact with participants to confirm each visit, and to reschedule in 
case of a missed visit. 
 


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5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION 
5.4.1 
Reasons for Withdrawal or Termination 
 A participant may withdraw from the study at any time or for any reason without being 
obliged to divulge their reason for doing so to the investigators or clinic staff.  
 A participant may be withdrawn from the study if there are unacceptable AEs, laboratory 
abnormalities or any other medical condition or situation including distress due to effects 
of any study procedure or medication.  
 A participant may be withdrawn from the study if in the opinion of the treating clinician 
the participant’s interests are best served by withdrawing from the study.  
 A participant may be withdrawn from the study if the participant meets an exclusion 
criterion (either newly developed or not previously recognized) that precludes further 
study participation. 
5.4.2 
Handling of Participant Withdrawals or Termination 
Participants, who do not receive the IP (i.e. Vivitrol), for any reason, are not considered study 
failures. A participant may be discontinued from the study at any time if the participant, 
investigator, or Sponsor determines that it is not in the best interest of the participant to 
continue participation. Reasons for discontinuation may include:  
 Adverse event 
 Withdrawal of participant 
 Lost to follow-up 
 Study terminated by investigator 
 Pregnancy 
 Clinical worsening  
 Other 
5.4.2.1 Participant Monitoring and Removal from Study 
The psychiatrist and/or therapist will assess appropriateness for continuation in the research 
study on a continuous basis and will remove from the trial participants with significant 
clinical deterioration or noncompliance of a type which could be dangerous. Criteria for 
removal from the study will include: 
1. 
Clinical deterioration which cannot be managed safely in the context of outpatient 
treatment. This would include a participant who becomes suicidal, or a participant 
who goes on drug binges (including non-opiate drugs). 
2. 
Elevation of liver enzymes >3 times normal. The PI or a study physician is available 
24 hours/day by phone in case of emergency. 
For those who withdraw from the study may request to withdraw from data collection and 
have no further contact with study site. Participants shall be informed that for a period of time 
30 days after their last Vivitrol injection there may a risk that opioid based medication may 
have a reduced affect. There is no option to remove Vivitrol from a participant. 


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5.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to PI and Sponsor. If the 
study is prematurely terminated or suspended, the PI will promptly inform the NYSPI IRB, 
Data Safety Monitoring Panel (DSMP), FDA and will provide the reason(s) for the 
termination or suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
 Determination of unexpected, significant, or unacceptable risk to participants 
 Insufficient compliance to protocol requirements 
 Data that are not sufficiently complete and/or evaluable 
Study may resume once concerns about safety, protocol compliance, data quality are 
addressed and satisfy the Sponsor, NYSPI IRB, DSMP and FDA. 
 
 






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1. Administer the suspension by deep intramuscular (IM) 
injection into a gluteal muscle, alternating buttocks per 
monthly injection. 
2. If blood aspirates or the needle clogs, do not inject. 
Change to the spare needle provided in the carton and 
administer into an adjacent site in the same gluteal region, 
again aspirating for blood before injection. 
3. Inject the suspension in a smooth and continuous motion. 
6.1.2.3 Disposal 
Dispose of as per manufacturer’s instructions. 
6.1.3 
Product Storage and Stability 
The entire dose kit should be stored in the refrigerator (2-8 °C, 36-46 °F). Unrefrigerated, 
VIVITROL Microspheres can be stored at temperatures not exceeding 25 °C (77 °F), for no 
more than 7 days prior to administration. Unrefrigerated Vivitrol should not be exposed to 
temperatures above 25 °C (77 °F). VIVITROL should not be frozen. 
6.1.4 
Preparation 
Refer to manufacturer’s product information sheet. 
6.1.5 
Dosing and Administration 
Participants shall be dosed as per the schedule outlined in Table 7-1. 
6.1.6 
Route of Administration 
Intramuscular injection in the buttock region (gluteal muscle) as per manufacturer’s product 
information sheet. 23 
6.1.7 
Dose Adjustments/Modifications/Delays 
Not applicable 
6.1.8 
Duration of Therapy 
Time in therapy: 196 days 
Total anticipated study length (including recruitment): 9 months 
6.1.9 
Tracking of Dose 
All participants will be administered a single Vivitrol injection into the gluteal muscle as per 
the schedule in Table 7-1, alternating between left and right gluteal muscle as tolerated, with 
the exact site being recorded.  
All follow up visits will check for AE’s related to the IP and where appropriate any injection 
site reactions.  


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6.1.10 Device Specific Considerations 
Not applicable. 
6.2 
STUDY AGENT ACCOUNTABILITY PROCEDURES 
Vivitrol for the study shall be sourced from a commercial supplier by the PI. The PI (or 
delegated study personnel) will sign that they have received all IP. IP will be kept in a 
securely locked refrigerated cabinet under appropriate temperature conditions and a drug 
inventory and temperature log maintained. All unused supplies must be accounted for and 
destroyed with an appropriate certificate of destruction in the event it is not used. 
 
 
 


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7 
STUDY PROCEDURES AND SCHEDULE 
7.1 
STUDY PROCEDURES/EVALUATIONS  
7.1.1 
Study Specific Procedures 
7.1.1.1 Screening  
The Screening Visit (conducted at Clinilabs) will include assessments necessary to determine 
study eligibility. The nature of the study and its risks and benefits will be explained to the 
participant by the study clinician who will also obtain a written informed consent from each 
potential participant prior to the administration of any study-specific procedures. The most 
important aspects of the protocol such as the IP administration are discussed in great detail. 
The study clinician (MD or PA) will perform a medical and psychiatric evaluation including 
a medical history and a physical examination. Medical staff or certified research assistants 
obtain electrocardiogram (ECG) and blood for complete blood count with differential, 
chemistry profile, liver function tests and pregnancy tests (if applicable). Urine is obtained 
for urinalysis and toxicology.  
7.1.1.2 Recruitment Visit 
Study-trained medical professionals such as a physician or a physician assistant that has been 
medically trained by the study PI to consent participants to the study and provide them with 
all necessary medical information will discuss questions related to the study procedure and 
the consent form. During the Recruitment Visit (conducted at Clinilabs) a study-trained 
medical professional confirms that a participant meets all inclusion/exclusion criteria, is 
medically healthy to participate in the study. A study-trained medical professional also 
reviews and signs the inclusion/exclusion checklist and signs off on enrollment 
documentation. A procedure note for the medical chart will be included and signed verifying 
that a study-trained medical professional reviewed results of the evaluation and obtained 
informed consent. Following study enrollment, a study-trained medical professional assumes 
medical responsibility and arranging hospitalization for IP administration at Clinilabs 
followed by in-patient care at Clinilabs. 
7.1.1.3 Naloxone challenge test (NCT) 
All participants will undergo an NCT at Clinilabs prior to IP administration. Participants will 
receive 0.8 mg naloxone, IM, followed by q10 minutes observation by study clinician or 
nurse over 30 minutes for signs and symptoms of opiate withdrawal.  
Naloxone injection may cause withdrawal symptoms such as nausea, vomiting, diarrhea, 
stomach pain, fever, sweating, body aches, weakness, running nose, goosebumps, shivering, 
increased heart rate, and anxiety. Most of these effects will wear off after 20-30 minutes and 
treatment is usually not needed but in case of severe symptoms, participants will be offered a 
dose of clonidine 0.1 mg and/or clonazepam 0.5 mg. In that case, participants will be 
monitored for up to 6 hours until all symptoms resolve, and they can be released. 
If a participant passes the NCT then they will progress to IP administration with the injection 
procedure (see Section 7.1.1.4).  
7.1.1.4 Injection procedure (initial) 
Following a successful NCT, the injection of IP (Vivitrol), is to be performed as per the 
manufacturer’s instructions23. The injection will be performed at the Clinilabs site. 
Participants will then remain at the Clinilabs research facility for 48 hours so that intensive 


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portion of the blood collection can occur. 
7.1.1.5 Injection procedure (repeat dose) 
There are 4 instances whereby participants will be re-administered Vivitrol 28 days apart 
with no intensive blood monitoring scheduled following re-administration of Vivitrol and no 
overnight stay. These are for Vivitrol injections 2, 3, 4 and 5 as outlined in Table 7-1. In these 
instances, participants will be seen on an out-patient basis at Clinilabs for their re-
administration of Vivitrol. Just prior to re-administration of Vivitrol, a NTX blood sample 
will be collected to capture the Vivitrol/naltrexone trough level. The actual time of each PK 
sample collection shall be recorded relative to the re-administration of Vivitrol. 
There are 2 instances whereby participants are administered Vivitrol injections and then 
remain at the Clinilabs research facility for intensive blood collections. These instances, 
Vivitrol injections 1 and 6, are detailed in depth in the admissions descriptions of 7.3.3.1, 
7.3.3.2, 7.3.3.3 and 7.3.3.4. 
7.2 
LABORATORY PROCEDURES/EVALUATIONS 
7.2.1 
Clinical Laboratory Evaluations 
Samples will be collected in accordance with Clinilab’s procedures and sent for analysis to 
Lab Corp.  
For the following test, 4.5 mL of blood will be collected in 1 x EDTA tube: 
 [FBC] Full Blood Count 
For the following tests, 5 mL of blood will be collected in 1 x SST tubes: 
 [EUC] Electrolytes, Urea, Creatinine 
 [LFT] Liver function Tests (bilirubin, ALP, GGT, ALT, ALB, TP) 
For the following tests, a sample of urine is collected:  
 Urinalysis; LEU (Leucocytes), NIT (Nitrite), PRO (Protein), pH, BLD (Blood), SG 
(Specific Gravity), KET (Ketones), GLU (Glucose) 
 [UDS] Full drug screen including buprenorphine assay. 
Pregnancy test: a blood test is done initially, with urine tests done monthly afterwards. A 
blood test will be used to confirm a positive urine result. 
7.2.2 
Other Assays or Procedures 
7.2.2.1 Naltrexone Blood Assay 
1 x 10 mL of whole blood in Na Heparin tubes (9 mL). Samples will be centrifuged for 
15 min at 2,000 rpm. Plasma will then be extract and stored in suitable containers (1.5 mL 
Eppendorf’s) for storage at -80ºC for transport to WuXi laboratories under dry ice in batches 
for free (unconjugated) NTX and free (unconjugated) 6βN analysis.  
7.2.3 
Total amount of Blood to be collected  
The amount of blood drawn for the study is: 
 Total LFT, EUC and FBC = 180.5 mL (18 x 9.5 mL) 


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 Pregnancy testing (Female participants only) = 4 mL (during the trial, a blood test will 
be used to confirm a positive urine result) 
 Total blood samples for NTX / 6βN 
- 387 mL (43 x 9 mL)  
 There is also the potential for further bloods to be taken on any un-scheduled visit for 
PK bloods (9 mL) and follow-up visit for outstanding AEs (LFT, EUC and FBC 
9.5 mL) post end of trial.  
The total scheduled blood collection is approximately 581.5 mL over the period of 196 days.  
7.2.4 
Specimen Preparation, Handling and Storage 
7.2.4.1 Naltrexone PK Blood Samples 
All NTX blood samples will be collected in 1 x 10.0 mL Na Heparin tubes (9 mL) and stored 
in the study site refrigerator at 0-4°C until specimen preparation.  
Specimen preparation will be carried out at study site within 24 hours. This will involve 
centrifugation of the blood sample to enable plasma separation. Plasma will be extracted and 
stored in suitable containers (1.5 mL Eppendorf’s) and stored at -80°C. When batches of 
greater than 50 samples are available these can then be shipped on dry ice to WuXi 
Laboratories for analysis. Backup samples will remain stored at Clinilabs for the duration of 
the trial.  
7.2.5 
Specimen Shipment 
Plasma will be stored for batch shipment to WuXi Laboratories, 107 Morgan Lane, 
Plainsboro, NJ, 08536 for analysis. Storage of samples at -80°C will be done at Clinilabs. 
Shipment of samples from Clinilabs to WuXi will be done under dry ice. 
7.3 
STUDY SCHEDULE 
7.3.1 
Screening Visit 
Participant shall be screened for inclusion and exclusion criteria and overall suitability for the 
study. 
 Obtain informed consent for screening. 
 Review medical history to determine eligibility based on inclusion/exclusion criteria. 
 Review medications history to determine eligibility based on inclusion/exclusion criteria. 
 Perform medical examinations, including Patient Health Questionnaire (PHQ-9), Beck 
Depression Inventory (BDI)-II, and C-SSRS to determine eligibility based on 
inclusion/exclusion criteria. 
 Concomitant medication review 
 Collect blood for LFT, FBE and EUC. 
 Collect blood for NTX and 6βN measurement. 
 Collect blood/urine for pregnancy test in female participants. 


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 Self-reported substance use and UDS 
7.3.2 
Recruitment 
At the Recruitment visit the following will take place; 
 Obtain informed consent for IP administration. 
 Concomitant medication review 
7.3.3 
IP Administration (in-patient care) 
7.3.3.1 Admission Day 0 
Participants will be admitted to Clinilabs where they will complete the PHQ-9, BDI-II, 
Substance Use assessment, concomitant medication review, AE monitoring and provide a 
blood/urine sample for pregnancy testing. Each participant will then undergo the NCT to 
confirm absence of opiate physical dependence. Participants will be scheduled to for 
administration of Vivitrol at Clinilabs as outlined in section 7.1.1.4. When feasible, 
participants will be fitted with the IV cannula to aid in the collection of blood sample for the 
first 48 hours. There shall be no use of heparin to keep the cannula clear as this may affect the 
blood analysis of NTX and 6βN. Processing and storage of blood samples shall be done as per 
section 7.2.4.1. 
NTX blood samples (see section 7.2.4.1) will be collected at the following time points: 
baseline (before Vivitrol administration), 1 hour ±15 min, 2 hours ±15 min, 4 hours 30 min, 
8 hours 60 min, and 12 hours 60 min. The actual time of each PK sample collection shall 
be recorded. 
Participants will also be monitored for AEs, Vital Signs and concomitant medication review. 
7.3.3.2 Admission Day 1 
NTX blood samples (see section 7.2.4.1) will be collected at 24 hours 2 hours, 36 hours ±2 
hours and 42 hours ±2 hours after Vivitrol administration. The actual time of each PK sample 
collection shall be recorded. 
Participants will also be monitored for AEs and concomitant medication review. 
7.3.3.3 Admission Day 2 
NTX blood samples (see section 7.2.4.1) will be collected at 48 hours 2 hours after Vivitrol 
administration. The actual time of each PK sample collection shall be recorded.  
Participants will also be monitored for AEs and concomitant medication review. 
Participants will then be discharged and provided with a timetable for their follow-up visits, 
which will be carried out at Clinilabs. 
7.3.3.4 Admission Day 140 to 142 
NTX blood samples (see section 7.2.4.1) will be collected at 140 days ± 1 day sample prior to 
Vivitrol re-administration. Participants will then be administered their sixth and final Vivitrol 
IM injection on Day 140 and the time recorded. NTX blood samples will be collected at 140 
days +1 hr ±15 min, 140 days +2 hr ±15 min, 140 days +4 hr ±30 min, 140 days +8 hr ± 60 
min, 140 days +12 hr ±60 min, 141 days ± 2 hr, 141.5 days ±2 hr, 141.75 days ±2 hr, 142 
days ±2 hr under in-patient care. The actual time of each PK sample collection shall be 
recorded. Participants will then be discharged and provided with a timetable for their follow-


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up visits, which will be carried out at Clinilabs. 
Participants will also be monitored for AEs, concomitant medication review, Substance Use: 
Self report & UDS. Where applicable, a pregnancy test will also be conducted.  
7.3.3.5 Vivitrol re-administration Day 28, 56, 84 & 112 (±1 day)  
There will be no intensive blood monitoring scheduled after administration of the 2nd, 3rd, 4th 
and 5th dose of Vivitrol as outlined in Table 7-1. In this instance, participants will be seen on 
an out-patient basis at Clinilabs for their re-administration of Vivitrol. Just prior to re-
administration of Vivitrol, blood samples will be taken for: LFT, EUC & FBE; and NTX PK 
analysis to capture the Vivitrol trough level. The actual time of each PK sample collection 
shall be recorded relative to the re-administration of Vivitrol. 
Participants will also be monitored for the following: AEs, PHQ-9, BDI-II, CSSRS, 
concomitant medication review, Vital signs, substance Use (Self report) and UDS. Where 
applicable a pregnancy test will also be conducted.  
7.3.4 
Follow-Up 
Participants will be instructed to attend the Clinilabs facility to continue study procedures as 
per the protocol time points outlined in Table 7-1. There are allowable variations in actual 
day of collection as long as the variation is recorded. At these time points, PK blood will be 
collected along with an injection Site assessment where applicable, PHQ-9 & BDI-II, 
concomitant medication review and AE monitoring.  
7.3.5 
Final Study Visit 
All participants will be required to attend the Clinilabs study site for a final visit with a study 
clinician as outlined in Table 7-1.  
Participants will be monitored for the following: AEs, PHQ-9, BDI-II, CSSRS, concomitant 
medication review, Vital signs, substance Use (Self report) and UDS. 
7.3.6 
Early Termination Visit  
Any participants that are withdrawn will be requested to attend Clinilabs for an early 
termination /withdrawal visit as outlined in Table 7-1. Participants will be advised of their 
option as outlined in in section 5.4.2. 
A follow-up visit may be conducted 30 days after the last scheduled on-study visit and is 
required only if a participant has ongoing AEs or laboratory abnormalities at the last on-study 
visit. An in-clinic follow-up visit must be conducted 30 days after the last scheduled on-study 
visit for an AE requiring laboratory testing for participants with the following conditions at 
the last on-study visit: ongoing AEs, SAEs regardless of attributability, any laboratory 
abnormalities considered to be AEs or potentially harmful to the participant. For in-clinic 
follow-up visits, assessments performed should reflect what is considered medically 
necessary to assess the event(s). 
7.3.7 
Unscheduled/Late Visits 
It is anticipated that some participants may miss or be delayed to some of their appointments. 
Every effort will be made to obtain blood samples at the scheduled dates, but blood samples 
will be accepted if they are taken late, with allowances made in the statistical analysis. 
Participants who miss appointments will be contacted by phone to encourage them to return 


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for as many appointments as possible. However, some dropouts are also anticipated so 
additional participants have been recruited to aim for a total of 4 completers. 
Participants will be asked to complete the following as a minimum; concomitant medication 
review, Vital signs, PK blood collection and AE monitoring. 
7.3.8 
AE Follow-up Visit 
A follow-up visit will be conducted 30 days after the last scheduled on-study visit. This visit 
is required only if a participant has ongoing AEs or laboratory abnormalities at the last on-
study visit. An in-clinic follow-up visit must be conducted 30 days after the last scheduled 
on-study visit for an AE requiring laboratory testing for participants with the following 
conditions at the last on-study visit: ongoing AEs, SAEs regardless of attributability, any 
laboratory abnormalities considered to be AEs or potentially harmful to the participant. For 
in-clinic follow-up visits, assessments performed should reflect what is considered medically 
necessary to assess the event(s). 
 




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7.4 
CONCOMITANT MEDICATIONS, TREATMENTS AND PROCEDURES 
All concomitant prescription medications including non-opiate medications taken at least 90 
days before study enrollment and during study participation will be recorded on the case 
report forms (CRFs). For this protocol, a prescription medication is defined as a medication 
that can be prescribed only by a properly authorized/licensed clinician. Medications to be 
reported in the CRF are concomitant prescription medications, over-the-counter medications 
and non-prescription medications. 
7.5 
PROHIBITED MEDICATIONS, TREATMENTS AND PROCEDURES  
The medications and substances listed below are prohibited for the specified time periods: 
 Buprenorphine, either as part of a maintenance program or any illicit/non prescribed is 
prohibited for the duration of the study. 
 Methadone is prohibited at least 14 days prior to Day 0 and for the duration of the Study.  
 All other opioids are prohibited for the duration of the study unless approved by the PI or 
study clinician (see section 7.7)  
 Oral naltrexone is prohibited for at least 30 days prior to Day 0 and for the duration of 
the study 
 Extended release naltrexone (e.g., Vivitrol) is prohibited for at least 60 days prior to 
Day 0 and for the duration of the study unless administered under this trial protocol. 
7.6 
PROPHYLACTIC MEDICATIONS, TREATMENTS AND PROCEDURES 
7.6.1 
Prophylactic Medications 
N/A 
7.7 
RESCUE MEDICATIONS, TREATMENTS AND PROCEDURES 
Since NTX acts as an opioid blocker, participants requiring pain relief during the study 
period will be offered appropriate pain medications e.g., tramadol, reginal blocks or partial 
opioid agonist such as buprenorphine.  
7.8 
PARTICIPANT ACCESS TO STUDY AGENT AT STUDY CLOSURE 
N/A 
7.9 
REIMBURSEMENT COSTS 
Participants will receive reimbursement as follows.  
 $50 for the screening visit 
 $50 for the consent visit 
 $200 for each inpatient day (4 days) 
 $50 for each scheduled outpatient visit (23 visits). Participants will receive an additional 
incremental bonus of $10 for each subsequent visit attended (Visit 1: $50, visit 2: 
$50+$10, Visit 3: $50+$20, Visit 4: $50 +$30 …). In case the scheduled visit is missed 
the value of the bonus is reset to the starting value of $10. This schedule is designed to 
reinforce adherence to all study safety assessments.  


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The total amount of reimbursement should a participant attend every scheduled visit is 
$4,580. If a participant is required to return for further PK or AE follow-up visits, or an 
unscheduled visit due to public health emergency then they will receive $50. In addition, 
participants will also receive $10 for transportation reimbursement.  
8 
ASSESSMENT OF SAFETY 
8.1 
SPECIFICATION OF SAFETY PARAMETERS  
Safety will be assessed on the basis of: 
 the incidence of death 
 the incidence of SAEs 
 the incidence AEs leading to discontinuation  
 the incidence common AEs 
 the incidence injection site reactions  
 laboratory abnormalities indicating hepatic problems (absolute values and changes over 
time)  
8.1.1 
Definition of Adverse Events (AE) 
AEs will be identified from the telephone interviews, face to face visits or from the CRF. 
They will be recorded on an AE form. 
8.1.1.1 Definitions 
An AE is any untoward medical occurrence in a clinical investigational participant 
administered a pharmaceutical product and which does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable or unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with 
the use of a medicinal IP, whether or not considered related to the medicinal product. An 
adverse event is any adverse change (developing or worsening) from the patient’s pre-
treatment condition, including concurrent illness. 
The investigator must make the distinction between exacerbation of pre-existing illness and 
lack of therapeutic efficacy. 
8.1.2 
Definition of Serious Adverse Events (SAE) 
A SAE is any adverse experience occurring during the study period that: 
 results in death; 
 is life-threatening; 
 results in inpatient hospitalization or prolongation of existing hospitalization; 
 results in a persistent or significant disability/incapacity; or 
 results in congenital anomaly/birth defect. 
A life-threatening AE is one that actually places the participant at immediate risk of death. A 
participant’s reaction is not classified as life-threatening simply because more severe 


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manifestations of the same adverse reaction can be fatal, e.g., mild airway obstruction is not 
life threatening but severe airway obstruction is. 
Hospitalization includes any inpatient admission, any transfer within a hospital for the 
purpose of treatment (for example, transfer of a participant from a psychiatric unit to a 
general medical unit) and prolongation of admission. Prolongation of hospitalization is 
defined as any extension of an inpatient hospitalization beyond the stay anticipated/ required 
in relation to the original reason for the initial admission, as determined by the investigator or 
treating physician.  
Study coordinators will report any new SAEs to the PI, NYSPI IRB, DSMP and Sponsor 
within 24 hours of first knowledge. 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT  
8.2.1 
Severity of Event 
 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. 
8.2.2 
Relationship to IP 
The clinician’s assessment of an AE's relationship to the IP (i.e. Vivitrol) is part of the 
documentation process, but it is not a factor in determining what is or is not reported in the 
study. If there is any doubt as to whether a clinical observation is an AE, the event should be 
reported. All AEs must have their relationship to study agent assessed. In a clinical trial, the 
IP must always be suspect. To help assess, the following guidelines are 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 fulfil 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” 


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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. 
8.2.3 
Expectedness  
8.2.3.1 Adverse Events from the use of Vivitrol 
Common side effects of Vivitrol may include: 
 sleepiness 
 headache 
 dizziness 
 vomiting 
 decreased appetite 
 painful joints 
 muscle cramps 
 cold symptoms 
 trouble sleeping 
 toothache 
Serious side effects may include: 
 Depressed mood 
 Pneumonia, symptoms include; 
o shortness of breath or wheezing 
o coughing that does not go away 
 Serious allergic reactions, symptoms include; 
o skin rash 
o swelling of your face, eyes, mouth, or tongue 
o trouble breathing or wheezing 
o chest pain 
o feeling dizzy or faint 
 


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8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND 
FOLLOW-UP  
The occurrence of an AE or SAE may come to the attention of study personnel during study 
visits and interviews of a study participant presenting for medical care, or upon review by a 
study monitor. 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be 
captured on the appropriate CRF. Information to be collected includes event description, time 
of onset, clinician’s assessment of severity, relationship to study product (assessed only by 
those with the training and authority to make a diagnosis), and time of resolution/stabilization 
of the event. All AEs occurring while on study must be documented appropriately regardless 
of relationship. All AEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s 
condition deteriorates at any time during the study, it will be recorded as an AE. 
Changes in the severity of an AE will be documented to allow an assessment of the duration 
of the event at each level of severity to be performed. AEs characterized as intermittent 
require documentation of onset and duration of each episode. 
The PI will record all reportable events (as defined in 8.4) 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. 
In the event of study discontinuation for any reason, any ongoing AEs will be followed until 
resolution or until deemed stable by the PI, or until the participant is deemed by the PI to be 
lost to follow-up. If, in the opinion of the PI, it is necessary to monitor a participant beyond 
the safety follow-up visit, the follow-up period may be extended as necessary. In such 
instances, the Sponsor and the PI will agree to an acceptable follow-up schedule. The PI must 
maintain a record of all participants who fail to complete the study. The reason for study 
discontinuation will be made on the appropriate CRF. 
 
8.4 
REPORTING PROCEDURES  
8.4.1 
Adverse Event Reporting 
The Sponsor will inform the investigator of any new information that may impact the conduct 
of the trial or have an impact on the ethical acceptability of the trial. 
Investigator will keep records of all AE’s on an ongoing basis. Significant concerns or 
unexpected AE’s from Dr. Adam Bisaga and Dr. Ned Nunes are to be reviewed by the 
DSMB via email or conference call. The Sponsor will update the protocol regularly with any 
new safety information relating to the drug.  
8.4.2 
Serious Adverse Event Reporting 
All SAEs should be reported as appropriate to the Sponsor, NYSPI IRB, FDA and Data 
Safety Monitoring Panel (DSMP) except for those SAEs that the protocol or other document 
(e.g., Manufacturer’s labelling) identifies as not needing expedited reporting. The expedited 


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reports should be followed promptly by detailed, written reports. The reports should identify 
participants by unique code numbers assigned to the trial participants rather than by the 
participants' names personal identification numbers, and/or addresses.  
8.4.2.1 Management of SAE’s  
SAEs, as defined by the FDA, will be systematically evaluated at each clinic visit. Any SAE, 
whether or not related to IP, will be reported to the NYSPI IRB and DSMP. The initial SAE 
report will be followed by submission of a completed SAE report to both institutions. The PI 
and study monitor will evaluate SAEs and bring them to the attention of the DSMB at the 
next scheduled meeting or sooner it there are significant concerns. 
In the event that a participant either withdraws from the study or the investigator decides to 
discontinue a participant due to SAE, the participant will have appropriate follow-up medical 
monitoring. Monitoring will continue until the SAE has resolved or stabilized with no further 
change expected, is clearly unrelated to IP, or results in death. Outcome of SAEs will be 
reported to the NYSPI IRB and DSMP as soon as this information becomes available. A 
summary of the SAEs that occurred during the previous year will be included in the annual 
progress report to the NYSPI IRB, FDA & DSMP. 
8.4.3 
Reporting of Pregnancy 
Reporting of pregnancy will be to the treating physician, PI, NYSPI IRB and DSMP. There is 
no ability to remove a Vivitrol injection from a pregnant participant. Although it is not 
desirable to maintain a pregnant participant in a PK study as hormonal changes due to 
pregnancy may adversely affect the PK of the IP, as Vivitrol is currently an approved 
medication, there are no major concerns for the participant’s safety if they become pregnant. 
However pregnant participants will have their data after confirmed pregnancy analyzed 
separately in case there are changes in PK characteristics as a result of the pregnancy. Any 
pregnancies will also be reported to the FDA in annual progress reports.  
 
8.5 
STUDY HALTING RULES 
8.5.1 
Study Termination 
The Sponsor reserves the right to close the investigational sites or terminate the study at any 
time. The PI may initiate site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. Reasons for the early 
closure of an investigational site by the Sponsor or PI, or termination of a study by the 
Sponsor, may include but are not limited to:  
 failure of the PI to comply with the protocol, the Sponsor’s procedures, or with GCP 
guidelines 
 safety concerns 
 inadequate recruitment of participants by the PI 
Study termination will be reported to the PI, NYSPI IRB, DSMP and FDA. 
8.5.2 
On-Site Audits 
Representatives of the Sponsor’s quality assurance department may visit the site to carry out 


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an audit of the study in compliance with regulatory guidelines and the Sponsor’s standard 
operating procedures. Audits and clinical trial monitoring will also be carried out by the 
CRO, Clinilabs, during the trial period. These audits will require access to all study records, 
including source documents, for inspection and comparison with the CRFs. Participant 
privacy must, however, be respected. Similar auditing procedures may also be conducted by 
agents of any regulatory body reviewing the results of this study in support of a regulatory 
submission. The PI should immediately notify the Sponsor if they have been contacted by a 
regulatory agency concerning an upcoming inspection.  
 
8.6 
DATA AND SAFETY MONITORING PLAN ADMINISTRATION 
8.6.1 
Responsibility for data and safety monitoring (DSM) 
The study PI, Dr. Adam Bisaga, is required to be present for all DSMB meetings to provide 
reports for all accumulated data from the trial. The PI will also be primarily responsible for the 
implementation of any recommendations from the DSMB. The PI will be assisted in this duty 
by Dr. Edward Nunes, study Medical Monitor.  
8.6.2 
 Frequency of DSM 
Ongoing data and safety monitoring will be conducted weekly during research team meetings 
of the PI with the investigative team. Every three months, the PI and the medical monitor will 
review the number of participants enrolled, the number who completed the protocol, the 
number who dropped out of the protocol prior to completion (and reason why), any AEs, 
procedures for assuring participants privacy and confidentiality, and the quality and integrity 
of the data collected. Corrective action will be taken if needed. IRB study protocols and 
informed consent documents will be reviewed annually by the IRB. Reports of enrollment 
and retention and reporting of AEs are required with these renewals.  
In addition, all studies involving human participants are periodically and systematically 
reviewed by the New York State Quality Assurance Staff. These procedures assure protocol 
compliance by conducting unannounced reviews of participants' research charts, comparing 
research charts to the IRB protocol. All SAEs will be reported to the FDA (as appropriate) 
and the DSMB in a timely fashion. 
A separate DSMB (see section 8.6.3 for details) will meet quarterly and the PI and study 
monitor will evaluate SAEs and bring them to the attention of the DSMB at the next 
scheduled meeting or sooner it there are significant concerns. Ad hoc meetings may also 
occur if any study related issues arise during the course of the study. 
8.6.3 
DSMB Plan  
The DSMB will be chaired by Dr. John Rotrosen, a Professor of Psychiatry at New York 
University and a senior addiction pharmacotherapy researcher. Two additional faculty 
members from the division will join the DSMB; Dr. Elias Dakwar, an opioid dependence 
treatment investigator in the division, and Dr. Arthur R. Williams, another research 
psychiatrist in the division. In addition, two research physicians from outside of the division 
will join the DSMB, Dr. Jonathan Stewart, a senior investigator in the Department of 
Psychiatry at Columbia University and expert in mood disorder pharmacotherapy, and Dr. 
Sandra Springer, an infection disease specialist at Yale School of Medicine, who has extensive 
experience studying naltrexone use in treatment for patients with hepatitis and HIV.  


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The DSMB will meet before the study launch and quarterly to conduct initial and ongoing 
study review and review all AEs that occurred in the study. PI and study monitor will evaluate 
SAEs and bring them to the attention of the DSMB at the next scheduled meeting or sooner it 
there are significant concerns. For each SAE, the PI and covering physician will present a 
synopsis of how it occurred and how the incident was handled clinically so that DSMB can 
assess how the event was managed and if there are any recommendations that will maintain 
the high quality of care provided to research participants. Ad hoc meetings may also occur as 
needed to address study related issues. 
All DSMB members will be asked to submit in writing any potential conflict of interest 
pertaining to the study. The DSMB will prepare a report in response to any SAE review 
meetings and will submit a DSM report annually. Reports will be submitted to the Sponsor 
and other authorities as appropriate. This report will include the following:  
a) Brief description of the trial,  
b) Baseline socio-demographic characteristics,  
c) Retention and disposition of study participants,  
d) Quality assurance issues,  
e) Regulatory issues,  
f) AEs,  
g) SAEs 
h) Efficacy 
 
9 
CLINICAL MONITORING 
This study may be subject to audit or inspection by representatives from the NYSPI IRB, 
DSMB or FDA.  
Data from this study will be monitored by staff from the CRO, Clinilabs, for compliance with 
GCP principals. Monitoring will include review of CRFs and other study documents for 
protocol compliance, data accuracy and completeness. Monitoring will include review of the 
investigator’s site file and drug handling records. Clinilabs will be given direct access to 
source documents, CRFs and other study-related documents. By signing the informed consent 
form, the participant authorizes Clinilabs staff direct access to their medical records and the 
study data.  
 
 
 


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10 STATISTICAL CONSIDERATIONS 
10.1 STATISTICAL AND ANALYTICAL PLANS  
NTX (and 6βN) plasma concentration data will be explored by Non-Compartmental Analysis 
(NCA). Mean, median, standard deviation and coefficient of variation of parameters such as 
AUC0-28days, Ctrough, and Cmax will be reported for each day for which the parameter is 
available, which is the primary objective of this study. The Accumulation Ratio (AR) of these 
parameters comparing the sixth with the first administration will inform us if there is 
accumulation of NTX (and 6βN) and if this accumulation is substantial. This is a secondary 
objective of this study.  
Comparison of the cumulative AUC0-28days, as well as overall Cmax and Ctrough during six 
consecutive Vivitrol administrations with previously determined 6-month data after OLANI 
(as determined in study GM0017) will inform us about bioequivalence of the two 
formulations. This is an exploratory objective of this study. Appropriate paired statistics will 
be used to compare the first with the sixth Vivitrol administration and to compare 6 months 
of Vivitrol with six months of OLANI.  
10.2 STATISTICAL HYPOTHESES 
N/A 
10.3 ANALYSIS DATASETS 
 
The analysis will be performed based on Intention-to-Treat and Per-Protocol in all 
participants enrolled. Assessment of primary outcomes will be performed on participants who 
complete at least 75% of applicable time points. 
10.4 DESCRIPTION OF STATISTICAL METHODS 
10.4.1 General Approach 
Pharmacokinetic parameters will be assessed from the NTX and 6βN plasma data using PK 
software (Phoenix Winnonlin, Princeton, NJ) and expressed and tabulated as a mean, median, 
standard deviation and co-efficient of variation for each administration of Vivitrol.  
Participants who submitted at least 75% valid pharmacokinetic blood samples from all study 
arms shall be measured for pharmacokinetic parameters of Cmax, Ctrough, Tmax, AUC0-28days and 
AUC0-∞.  
Accumulation of NTX and its metabolite is investigated using the Accumulation Ratio (AR) 
for AUC0-28days, AUC0--∞, Cmax and Ctrough. An accumulation ratio of 1 (e.g., AUC0-28days, 6th 
administration / AUC0-28days, 1st administration) indicates that there is no accumulation.  
As an exploratory endpoint we will also compare the cumulative AUC0-28days during 6 
consecutive administrations of Vivitrol with the AUC0-6months after OLANI, which was 
determined for each of these patients in study GM0017. In addition, Cmax and Ctrough will be 
compared for both formulations. Comparisons will be done using the ratio of the geometric 
mean of these parameters for each formulation.  
10.4.2 Analysis of the Primary Endpoint 
The pharmacokinetic parameters of Cmax, Ctrough, Tmax, AUC0-28days and AUC0-∞ will be 
assessed from participants who submitted at least 75% valid pharmacokinetic blood samples. 
The data will be investigated using exploratory statistics. Means, medians, Standard 


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Deviations and Coefficients of Variation will be calculated for each administration and will 
be tabulated. 
10.4.3 Analysis of the Secondary Endpoint(s) 
We will calculate the Accumulation Ratio (AR) for AUC0-28days, Cmax and Ctrough by 
comparing the parameter after one administration with the same parameter after another, e.g., 
AUC0-28days, 6th administration / AUC0-28days, 1st administration. An AR of 1 (or a value close to 1) 
indicates little to no accumulation.  
This analysis will be accompanied by visual inspection of the plasma concentration time 
curves of NTX and its metabolite, which will be plotted graphically. The visual inspections 
and comparisons of the curves are exploratory endpoints of this study.  
Visual inspection of the curves will also inform us if the plasma concentration time profile 
after the first administration is similar to that after the sixth administration of Vivitrol.  
Visual inspection of the Vivitrol curves and comparison with the visual inspection of the 
OLANI (as determined in GM0017) curves in the same patients might also inform us if 
earlier identified rapid metabolizers of the OLANI formulation are also rapid metabolizers of 
the Vivitrol formulation.  
Use of opioids, cocaine, marijuana, and alcohol for each day of the study will be determined 
based on results of urine toxicology and self-report. Proportion of days with substance use for 
each participant will be summarized.  
10.4.4 Safety Analyses 
The frequency of AEs, SAEs, adverse drug reactions (ADR), and suspected unexpected 
serious AE will be recorded. Additionally, counts of the number of laboratory values that fall 
outside of the normal range will be used to assess safety.  
10.4.5 Adverse Events 
After coding of AEs according to the Medical Dictionary for Regulatory Activity 
classification (MedDRA) and assignment to a system organ class and preferred term, all AEs 
recorded during the course of the trial will be listed by the participant number. 
An AE will be considered as 'treatment emergent' if it occurred after the first drug 
administration of each period or if it was present prior to drug administration but exacerbated 
after the drug administration. All other adverse events will be considered “pre-treatment.”  
In the case where it is not possible to define an AE as being treatment emergent or not, the 
AE will be classified as treatment emergent as the most conservative approach. 
A summary table describing all the TEAEs occurring during the trial will be produced overall 
and by treatment sequence using frequency of events and number and percentage of subjects 
experiencing these events. In addition, all TEAEs will be tabulated by intensity and 
relationship to drug in the same manner. Multiple occurrences of the same TEAE in one 
participant during the same treatment in the trial will be counted as multiple events in the 
frequency counts for adverse events. If a participant experiences more than one occurrence of 
the same TEAE during the same treatment in the trial, the participant will only be counted 
once using the worst severity and the strongest relationship.  
All adverse events leading to trial or treatment discontinuation will be listed by treatment 
sequence and participant.  


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All SAEs will be listed by treatment sequence and participant.  
10.4.6 Adherence and Retention Analyses 
The percentage of participants that complete the desired number of follow up blood 
collection points will be calculated and presented with 95% confidence intervals.  
10.4.7 Baseline Descriptive Statistics 
Baseline characteristics will be calculated using mean, standard deviation, median, 
interquartile range, percentages and 95% confidence intervals (where appropriate).  
10.4.8 Planned Interim Analyses 
10.4.8.1 Safety Review 
As per AE reporting, AEs will be collated and reviewed semi-annually by the DSMB. This 
may include crude rates of type specific AEs; however, no formal interim analysis will be 
conducted.  
10.4.8.2 Efficacy Review 
No interim efficacy analysis will be performed.  
10.4.9 Additional Sub-Group Analyses 
No sub-group analysis will be performed.  
10.4.10 Multiple Comparison/ Multiplicity 
No adjustment will be made for multiple comparisons.  
10.4.11 Tabulation of Individual Response Data 
Individual PK and safety data will be tabulated for each time point and included in the 
appendices of the final study report.  
10.4.12 Exploratory Analyses 
No exploratory analysis will be conducted.  
10.5 SAMPLE SIZE  
At the completion of the study, it is desirable that a minimum of 12 participants will complete 
a minimum of 75% blood collection time points. 
10.6 SOFTWARE 
PK parameters are determined using Non-Compartmental Analysis embedded within Phoenix 
WinNonlin Pharmacokinetics software (Certara, Princeton, NJ). 
 
 


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11 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
Direct access to source data/documents will be provided to the Sponsor, trial-related 
monitoring, audits, NYSPI IRB, and regulatory inspection(s). 
 
12 QUALITY ASSURANCE AND QUALITY CONTROL 
QC procedures will be implemented beginning with the data entry system and data QC 
checks that will be run on the database will be generated. Any missing data or data anomalies 
will be communicated to the site(s) for clarification/resolution. 
Following written SOPs, the monitors will verify that the clinical trial is conducted and data 
are generated, documented (recorded) and reported in compliance with the protocol, GCP and 
the applicable regulatory requirements (e.g., GLP & GMP). 
The investigational site will provide direct access to all trial related sites, source 
data/documents and reports for the purpose of monitoring and auditing by the Sponsor, CRO 
and inspection by local and regulatory authorities. 
 
13 ETHICS/PROTECTION OF HUMAN PARTICIPANTS 
13.1 ETHICAL STANDARD 
The study will be conducted in accordance with the guidelines and principles outlined in the 
International Conference on Harmonization - Standards of Good Clinical Practice24 and the 
Declaration of Helsinki25.Compliance with these standards ensures that the rights, safety and 
well-being of participants are consistent with the above principles. 
13.2 INSTITUTIONAL REVIEW BOARD  
The investigator will obtain NYSPI IRB approval for this study. Initial IRB approval as well 
as all materials approved by the IRB for this study, including the participant consent form and 
recruitment materials.  
Annual Reports describing the study progress and all AEs will be provided to the NYSPI 
IRB, along with a final study report by the PI. A copy of this report will also be provided to 
the Sponsor. 
13.3 INFORMED CONSENT PROCESS 
13.3.1 Consent/Assent and Other Informational Documents Provided to Participants  
All study participants will be provided with a Participant Information Consent (PIC) 
describing the study and providing sufficient information so that they are able to make an 
informed decision about their participation in the trial. The PIC form will be submitted with 
the research application for review and approval by the IRB.  
13.3.2 Consent Procedures and Documentation  
The PI (or authorized designee) will ensure that the participant is given full and adequate oral 
and written information about the nature, purpose, potential and possible risks and benefits of 
the study. Each prospective participant will receive an IRB-approved PIC that summarizes 


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the pertinent study information and will be given ample time to read the form and ask 
questions about the study. All information is to be provided in a language understandable to 
the participant and must not include any language that waives the participant’s legal rights. 
Prospective participants must also be informed of their right to withdraw consent without 
prejudice at any time during the study. If the participant chooses to participate, he/she must 
sign the PIC before any study-specific procedures are conducted. 
13.4 PARTICIPANT AND DATA CONFIDENTIALITY 
All data generated in this study will remain confidential. All information will be stored 
securely. Participant information will only be disclosed to authorized individuals i.e. research 
personnel listed on the Delegation of Authority Log who have signed a confidentiality 
agreement with the PI to undertake research related procedures.  
All participant data will be de-identified by use of an alphanumeric study coding system. 
Participant identification will be recorded on a Master Participants List held in-confidence by 
the PI in a locked cabinet separate to the de-identified data sheets. 
Personal information recorded in study documentation or an electronic database will only be 
accessed by authorized study personnel. Personal computer access will be password protected 
and also limited to authorized study personnel. 
 
13.4.1 Research Use of Stored Human Samples, Specimens or Data  
13.4.1.1 Naltrexone bloods 
All NTX blood samples will be collected in 1 x 10 mL Na Heparin tubes (9 mL) and stored in 
the study site refrigerator at 0-4°C until specimen preparation.  
Specimen preparation will be carried out at study site within 24 hours. This will involve 
centrifugation of the blood sample to enable plasma separation. Plasma will be extracted and 
stored in suitable containers (1.5 mL Eppendorf’s) and stored at -80°C. When batches of 
greater than 50 samples are available these can then be shipped on dry ice to Xenobiotic 
Laboratories for analysis. Backup samples will remain stored at Clinilabs for the duration of 
the trial. All samples will be analyzed for free (unconjugated) NTX and free (unconjugated) 
6βN quantification. It is anticipated that samples will be prepared and split into 4 aliquots, 
with 2 being used for analysis and 2 serving as a backup being stored de-identified in a -80°C 
freezer. Samples will be kept for 5 years after the completion of the trial, after which time 
they will be destroyed.  
13.5 FUTURE USE OF STORED SPECIMENS  
Data collected for this study will be analyzed and stored at study site, as per the site’s 
standard protocols.  
 
 


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14 DATA HANDLING AND RECORD KEEPING 
14.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
An electronic Case Report Form (eCRF) will be designed to record data required by the 
protocol and collected by study personnel. An eCRF will be completed for each participant.  
A confidential list of participant names, contact details, and screening numbers will be kept 
by the study site. eCRF data removed from the study site will be identified by the screening 
number and will not contain participant names or contact details. 
Data collection is the responsibility of the clinical trial staff at the site under the supervision 
of the site PI. The PI is responsible for ensuring the accuracy, completeness, legibility and 
timeliness of the data reported. All source documents should be completed in a neat, legible 
manner to ensure accurate interpretation of data. 
14.2 STUDY RECORDS RETENTION 
Retention and storage of essential clinical study documents (e.g., worksheets, drug 
accountability forms, and other administrative documentation) shall be governed by the terms 
and conditions of NYSPI.  
• 
Ten years after discontinuation of the study, or  
• 
Two years following the date a marketing application is approved for the study drug for 
the indication for which it is being investigated pursuant to the study, or 
• 
If no application is to be filed or if the application is not approved for such indication, 
until 2 years after the date the study is terminated.  
Participants’ medical files should be retained in accordance with the applicable legislation 
and in accordance with the maximum period of time permitted by the hospital, institution, or 
private practice 
14.3 PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, SOP’s and GCP 
requirements. The noncompliance may be either on the part of the participant, the PI, or the 
study site staff. As a result of deviations, corrective actions are to be developed by the site 
and implemented promptly. 
The PI should not implement any deviation from, or changes of the protocol without 
agreement by the Sponsor and prior review and documented approval/favorable opinion from 
NYSPI IRB, except where necessary to eliminate an immediate hazard(s) to trial participants, 
or when the change(s) involves only logistical or administrative aspects of the trial (e.g., 
change in monitor(s), change of telephone number(s)). 
If the PI implements a deviation from, or a change of, the protocol to eliminate an immediate 
hazard(s) to trial participants, without prior approval/favorable opinion from NYSPI IRB. As 
soon as possible, the implemented deviation or change, the reasons for it, and, if appropriate, 
the proposed protocol amendment(s) should be submitted:  
 To NYSPI IRB for review and approval/favorable opinion,  
 To the Sponsor for agreement and, if required,  
 To the regulatory authority (e.g., FDA). 
The PI, or person designated by the PI, should document and explain any deviation from the 
approved protocol. 


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14.4 PUBLICATION AND DATA SHARING POLICY 
 
The data will be entered and analyzed by the PI, Clinilabs, and additional study personnel 
from NYSPI. A Clinical Pharmacology Study Report will be issued which may form the 
basis of a manuscript intended for publication. Any publications arising from this study will 
be published by a process of peer review. 
 
15 STUDY ADMINISTRATION 
15.1 STUDY LEADERSHIP 
 
The study leadership will be composed of the PI, the Clinilabs Responsible Clinician Dr. 
Maha Ahmad, the Sponsor Representative, and site 1 representative Dr. Edward Nunes (See 
section 1) 
 
16 CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence 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 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. 
 
 












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19 LITERATURE REFERENCES 
1. 
Wall, M. E., Brine, D. R. & Perez-Reyes, M. The metabolism of naltrexone in man. 
NIDA Res. Monogr. 28, 105–31 (1981). 
2. 
Alkermes. FDA Psychopharmacologic Drugs Advisory Committee Meeting Vivitrol® 
(naltrexone for extended-release injectable suspension) NDA 21-897. 165 (2010). 
3. 
Wall, M. E., Perez-Reyes, M., Brine, D. R. & Cook, C. E. Naltrexone disposition in 
man after subcutaneous administration. Drug Metab. Dispos. 12, 677–82 (1984). 
4. 
Rukstalis, M. R., Stromberg, M. F., O’Brien, C. P. & Volpicelli, J. R. 6-beta-naltrexol 
reduces alcohol consumption in rats. Alcohol. Clin. Exp. Res. 24, 1593–6 (2000). 
5. 
McCaul, M. E., Wand, G. S., Rohde, C. & Lee, S. M. Serum 6-beta-naltrexol levels are 
related to alcohol responses in heavy drinkers. Alcohol. Clin. Exp. Res. 24, 1385–91 
(2000). 
6. 
Meyer, M. C., Straughn, A. B., Lo, M. W., Schary, W. L. & Whitney, C. C. 
Bioequivalence, dose-proportionality, and pharmacokinetics of naltrexone after oral 
administration. J. Clin. Psychiatry 45, 15–9 (1984). 
7. 
Porter, S. J., Somogyi, A. A. & White, J. M. Kinetics and inhibition of the formation of 
6beta-naltrexol from naltrexone in human liver cytosol. Br. J. Clin. Pharmacol. 50, 
465–71 (2000). 
8. 
Bell, J. R. et al. A pilot study of naltrexone-accelerated detoxification in opioid 
dependence. Med. J. Aust. 171, 26–30 (1999). 
9. 
Duramed Pharmaceuticals. REVIA®, US Package Insert. Reference ID: 3383348 
(2013). 
10. 
Hulse, G. K. & Basso, M. R. The association between naltrexone compliance and daily 
supervision. Drug Alcohol Rev. 19, 41–48 (2000). 
11. 
Gevirtz, C. Rapid Opioid Detoxification. JAMA 279, 1871 (1998). 
12. 
Brewer, C. Naltrexone implants for opiate addiction: New life for a middle-aged drug. 
Pharm. J. 267, 260 (2001). 
13. 
Brewer, C. Naltrexone: An ‘Antiabuse’ for heroin addicts? Pharm. J. 239, 182–183 
(1987). 
14. 
Wise, D. L. No Title. in Biopolymeric Controlled Release Systems (ed. Wise, D. L.) 
115–181 (CRC Press, 1984). 
15. 
Yamaguchi, K. & Anderson, J. M. In vivo biocompatibility studies of medisorb® 
65/35 D,L-lactide/glycolide copolymer microspheres. J. Control. Release 24, 81–93 
(1993). 
16. 
Schwope, A. D., Wise, D. L. & Howes, J. F. Lactic/glycolic acid polymers as narcotic 
antagonist delivery systems. Life Sci. 17, 1877–1885 (1975). 
17. 
Yolles, S., Leafe, T. D., Woodland, J. H. R. & Meyer, F. J. Long acting delivery 
systems for narcotic antagonists II: Release rates of naltrexone from poly(lactic acid) 
composites. J. Pharm. Sci. 64, 348–349 (1975). 
18. 
Chiang, C. N., Hollister, L. E., Kishimoto,  a & Barnett, G. Kinetics of a naltrexone 
sustained-release preparation. Clin. Pharmacol. Ther. 36, 704–8 (1984). 


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19. 
Maa, Y. F. & Heller, J. Controlled release of naltrexone pamoate from linear 
poly(ortho esters). J. Control. Release 14, 21–28 (1990). 
20. 
Pettinati, H. M., Gastfriend, D. R., Dong, Q., Kranzler, H. R. & O’Malley, S. S. Effect 
of Extended-Release Naltrexone (XR-NTX) on Quality of Life in Alcohol-Dependent 
Patients. Alcohol. Clin. Exp. Res. 33, 350–356 (2009). 
21. 
Krupitsky, E. Injectable extended-release naltrexone for the prevention of relapse to 
opioid dependence following opioid detoxification. Neuropsychiatry (London). 2, 355–
362 (2012). 
22. 
Johnson, B. A. et al. A pilot evaluation of the safety and tolerability of repeat dose 
administration of long-acting injectable naltrexone (Vivitrex) in patients with alcohol 
dependence. Alcohol. Clin. Exp. Res. 28, 1356–61 (2004). 
23. 
Alkermes. US Vivitrol Prescribing Information. (2020). Available at: 
https://www.vivitrol.com/content/pdfs/prescribing-information.pdf. (Accessed: 27th 
October 2020) 
24. 
Therapeutic Goods Administration. NOTE FOR GUIDANCE ON GOOD CLINICAL 
PRACTICE (CPMP/ICH/135/95). Department of Health And Aged Care (TGA 
Publications Office, 2000). 
25. 
World Health Organisation. World Medical Association Declaration of Helsinki. 
JAMA 310, 2191 (2013). 
 
 

ICF_001.pdf: 
#8082/GM019A PIC 0.3 
27 Oct 2021 Ver. 0.4  
1 
A PHARMACOKINETIC STUDY OF VIVITROL IN HEALTHY PARTICIPANTS 
Principal Investigator: Dr. Adam Bisaga, MD (646) 774-6155 
Overview: The aim of this study is to monitor naltrexone level in participants’ blood who will be receiving monthly 
administration of Vivitrol, which is an FDA-approved version of extended-release naltrexone. Naltrexone is an opioid 
blocker and Vivitrol is used to treat alcohol and opioid addiction. Vivitrol is administered by a single injection in the 
buttock region and is designed to release a steady dose of naltrexone for up to 28 days following each injection. Vivitrol 
injection will be administered 6 times, every 28 days, and the aim of the study is to measure the level of naltrexone in the 
blood through the study duration which is 196 days. 
Voluntary: As with all research, this is a voluntary study, and you do not have to participate if you do not want to.  Also, 
you may stop participating at any time. 
Procedures: This study is only offered to participants who completed study with naltrexone implant (#7698). If you 
decide to participate in this study, you will initially be assessed for eligibility. You will be provided with a dated schedule 
of visits once you are enrolled into the study. You will be asked to attend the research clinic for a screening visit, where 
you will be seen by the trial doctor who will discuss the study with you, ask questions about your medical and psychiatric 
history, obtain ECG and bloods, and give you a physical exam. Once you have given consent to participate in this trial, 
you will be admitted to the Clinilabs facility for 48 hours. While there, you will be given a naloxone challenge to ensure 
you do not have any opiates in your system. Afterwards, you will be given a Vivitrol injection which will release a steady 
dose of naltrexone for up to 28 days. Following the injection, you will give several blood samples while in the hospital. 
After you are discharged from the hospital you will be scheduled to attend the research clinic located at Clinilabs for your 
follow-up appointments. At each study visit, you will have a blood draw, be asked to provide urine samples which will be 
tested for the presence of drugs, complete safety questionnaires, be asked about side effects or issues since your injection, 
and new medications you have taken since the previous visit. Additionally, you will be given a Vivitrol injection every 
28 days for maximum of six times in the study. You will also be asked to fill in some questionnaires at your post 
discharge visits.  
Risks: Vivitrol is currently approved by the FDA for treatment and research purposes. 
1.
Participants who require narcotic painkillers for severe pain will have a greatly reduced effect
while naltrexone is being released from Vivitrol, and higher doses of high potency opioids
may need to be used or alternative, non-opioid treatments.
2.
Vivitrol injection may cause pain, irritation or inflammation at or near the site of
administration as a result of an allergic response or other inflammatory process.
3.
Known side-effects from naltrexone include difficulty sleeping, anxiety, nervousness,
abdominal pain/cramps, nausea and/or vomiting, low energy, join and muscle pain,
headache, loss of appetite, diarrhea, constipation, increased thirst, increased energy,
depressive mood, irritability, dizziness, skin rash, delayed ejaculation, erection dysfunction,
reduced sexual desire, and chills.
4.
Some studies have shown a reversible liver injury by elevated liver enzymes at naltrexone
doses which are much higher than those proposed in this study.
5.
Naloxone or naltrexone may cause withdrawal symptoms in people who have been taking opioids such as
prescription painkillers or heroin. Withdrawal symptoms include nausea, vomiting, diarrhea, stomach pain,
fever, sweating, body aches, weakness, running nose, goosebumps, shivering, increased heart rate, and anxiety.
6.
During the declared COVID-19 public health emergency, there is an increased risk related to the necessary
travel to the research clinic and the visit at the clinic. This may include a risk of getting exposed to the virus and
the risk of getting infected and developing an infection-related disorder (e.g. COVID-19).
Benefits: This research study is not meant to benefit you directly. This study is designed to collect information which 
will be used to determine whether extended release naltrexone implant could be used as a treatment for people with 
opioid use disorder, and to help obtain approval from the US Food and Drug Administration (FDA). 
Alternatives: Information is being collected for research purposes only. You may choose to not participate in this study. If 
you decide not to take part in this research study, it will have no effect on your medical care. You will not lose any 
benefits or access to treatment that you otherwise are entitled to if you don’t want to be in this study 
Compensation: The total compensation will depend on the total number of visits you will be scheduled for and make. 
We predict that on average your participation in the study may last 6 months in which case you will be compensated 
$4,580 if you make all scheduled visits. 
Questions: You may contact the study doctor, Adam Bisaga, MD at (646) 774-6155 with any questions. 
NCT04716881


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NEW YORK STATE PSYCHIATRIC INSTITUTE COLUMBIA UNIVERSITY 
DEPARTMENT OF PSYCHIATRY 
INFORMED CONSENT FOR PARTICIPATION IN RESEARCH 
A PHARMACOKINETIC STUDY OF VIVITROL IN HEALTHY PARTICIPANTS
I. Purpose and Overview 
Because you participated in the prior study (IRB#7698) in which you received the naltrexone implant, 
you are now invited to participate in a research study to investigate the pharmacokinetic parameters 
(changes in medication level in the blood) after receiving injections of Vivitrol, which is an FDA-
approved version of extended-release naltrexone. Naltrexone is an opioid blocker and Vivitrol is used 
to treat alcohol and opioid addiction. Vivitrol is administered by a single injection in the buttock region 
and is designed to release a steady dose of naltrexone for up to 28 days following each injection. 
Vivitrol injection will be administered 6 times, every 28 days, and the aim of the study is to measure 
the level of naltrexone in the blood through the study duration which is 196 days (approximately 6 
months).  
During the study you will receive a total of six injections. One injection will be given every 28 days 
into the muscle of the buttock region, and alternate buttocks will be used for each injection to minimize 
discomfort from repeated injections. Possible risks associated with the Vivitrol injection include an 
inflammatory reaction (itching, pain, swelling) to the injection material and the risk of liver damage. 
Any inflammatory response will naturally recover over a few days following administration or if 
severe, it can be treated with medication. The health of your liver will be monitored routinely over the 
course of the study.  
Vivitrol contains naltrexone in the form of small grains containing naltrexone which slowly dissolve 
over a month releasing the medication. The amount of naltrexone being released from the  
Vivitrol will be measured by collecting blood samples at regular time points for up to 196 days or 
 just over 6 months. In people with opioid addiction, naltrexone blocks the effects of opioids and 
reduces cravings, but the naltrexone itself has no opioid-like effects and is not a controlled substance.  
This study will be conducted by personnel from the New York State Psychiatric Institute (NYSPI), 
Columbia University Irving Medical Center (CUIMC),  and Clinilabs, with funding provided by the 
National Institute of Drug Abuse. 
II. Voluntary
Participation in this research study is voluntary. If you decide not to participate, or if you later decide 
to stop participating, you will not lose any benefits to which you are otherwise entitled. A decision not 
to participate or withdraw your participation will not affect your current or future treatment at the 
NYSPI or CUIMC. If applicable, you will be notified of significant new findings that may relate to 
your willingness to continue to participate. 


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III. Alternative Treatments/Alternative to Participation
Information is being collected for research purposes only. The alternative to participating is not to 
participate. If you decide not to take part in this research study, it will have no effect on your medical 
care. You will not lose any benefits or access to treatment that you are otherwise entitled to if you 
don’t want to be in this study. 
IV. Procedures
Study procedures are generally similar to procedures used in the prior study with naltrexone implant 
that you have participated in. 
If you decide to participate in this study, you will be initially assessed for your suitability to 
participate after signing consent for a screening evaluation. In order to determine possible eligibility 
for the research study, it is necessary for NYSPI and Clinilabs to know if you are currently participating 
in a clinical research study or have recently participated in one. NYSPI and Clinilabs use the Verified 
Clinical Trials (VCT) database to help determine whether potential clinical research subjects are 
participating or have recently participated in other clinical research studies. NYSPI and Clinilabs 
need information about your participation in other clinical research studies because it is important 
that you not participate in more than one clinical research study at a time involving investigational 
drugs or other investigational products. 
Additionally, you will be asked to undergo specific health related procedures to minimize the risk 
and spread of Covid-19. Upon entering the facility, you will be given a Covid-19 screening survey 
and have your temperature checked. You will also be asked to maintain proper hygienic measure 
like washing your hands, as well as maintaining the appropriate six feel social distance between 
you and other staff.  
If you are taking opioid painkiller medications or other opioids, you should not participate in this 
study, because the naltrexone could make you very sick and will block the effect of opioid 
painkillers for weeks after injection. If you are planning to get pregnant in the next year you should 
also not participate in this study. 
You will be asked to attend Clinilabs for a screening visit, where you will be seen by a study doctor 
who will check that you are suitable for the study, ask some questions about your medical and 
psychiatric history, general health, treatment history, your substance use and undergo a physical 
exam and have blood and urine samples collected, and if applicable a pregnancy test. If you have 
been assessed as suitable to participate in the study, you will then be asked to attend a recruitment 
visit where you will be asked to give your consent to participate in this trial. 
Once you have given your consent to participate in this trial, you will stay in the inpatient unit at 
Clinilabs for two nights. On the first day, you will be given a naloxone challenge test, where a dose 
of naloxone will be injected into your arm. If you have used any opiates, or opiate medications 
within the last few days, naloxone will cause you to have an opioid withdrawal reaction with 
symptoms such as nausea, vomiting, diarrhea, stomach pain, fever, sweating, body aches, weakness, 
running nose, goosebumps, shivering, increased heart rate, and anxiety. Most of these effects will 
wear off after 20-30 minutes and treatment is usually not needed. If you do experience severe 
symptoms, you will be offered treatment with medications such as clonidine and/or clonazepam to 
help alleviate your symptoms. You will be monitored for up to 6 hours until all symptoms resolve, 
and then you can be released from the unit. This circumstance will be considered a naloxone 
challenge test failure and you will not be included in the study. 


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4 
If you have no withdrawal reaction to naloxone, you will then be administered an injection of 
Vivitrol. Each injection contains small grains containing naltrexone suspended in approximately 
4mL of fluid. This fluid is injected into the muscular area of the buttock region. This injection is 
repeated every 28 days for a total of 6 injections. 
Prior to the first and sixth injection only, an IV line will be placed in your forearm to aid blood 
collection and administration of medications if needed. You will then be asked to give blood samples 
for testing at the following scheduled time points; 1, 2, 4, 8, 12, 24, 36, 42 and 48 hours after the 
Vivitrol injection.  
After you leave the Clinilabs you will be asked to return for your follow-up appointments and repeat 
injections according to the schedule outlined in the Table 1 below. All follow-up appointments will 
occur at the Clinilabs research unit and each visit will last about 30 minutes. At each follow-up visit, 
you will be asked about any medication that you have taken and if you have had any side effects or 
issues since your Vivitrol injection, and the doctor will assess the medication injection site. Blood 
(about 2 teaspoons) will be drawn at each follow-up visit to test the level of naltrexone that the 
Vivitrol is releasing into your system. At monthly follow-up visits, blood (another 2 teaspoons) will 
also be drawn for routine blood tests (blood chemistries and cell counts). At most follow-up visits 
you will also be asked to fill out some questionnaires about your general health and mental health, 
and to give urine samples that will be tested for the presence of drugs.  
During the monthly follow-up visits, you will undergo additional, second through fifth, Vivitrol 
injections.  For the final and sixth Vivitrol injection, you will be required to stay at Clinilabs for two 
overnights again and provide multiple blood samples at 1, 2, 4, 8, 12, 24, 36, 42 and 48 hours after 
the final injection, and afterwards you will return for follow-up visits.  
Once you are enrolled into the study, you will be provided with a detailed schedule of all required 
visits. You may be asked to attend further visits past day 196 if you have any ongoing medical issues 
relating to the trial or to give further blood samples to measure the level of naltrexone. 


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Table 1. Schedule of follow-up visits and procedures after the first injection 
Days after initial 
injection 
Information / Samples Collected 
Day 3 
Adverse Events (AE) Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 5 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 7 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 10 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 14 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 17 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 21 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 24 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 28 
AE Monitoring, Questionnaires, Blood (2 teaspoons), Liver test, Pregnancy test, 
Urine Drug screen, Vivitrol 2nd injection 
Day 56 
AE Monitoring, Questionnaires, Blood (2 teaspoons), Liver test, Pregnancy test, 
Urine Drug screen, Vivitrol 3rd injection 
Day 84 
AE Monitoring, Questionnaires, Blood (2 teaspoons), Liver test, Pregnancy test, 
Urine Drug screen, Vivitrol 4th injection 
Day 112 
AE Monitoring, Questionnaires, Blood (2 teaspoons), Liver test, Pregnancy test, 
Urine Drug screen, Vivitrol 5th injection 
Admission Day 140 
Blood (2 teaspoons), AE Monitoring, Questionnaires, Liver test, Pregnancy test, 
Urine Drug screen, Vivitrol 6th injection, Blood (10 teaspoons) 
Admission Day 141 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Admission Day 142 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 143 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 145 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 147 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 150 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 154 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 157 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 161 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 164 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 168 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 182 
AE Monitoring, Questionnaires, Blood (2 teaspoons) 
Day 196 
Physical and mental exam, ECG, Questionnaires, Liver test, Pregnancy test, AE 
Monitoring, Urine Drug screen, Blood (2 teaspoons) 
V. Risks and Inconveniences 
Vivitrol is approved by the FDA and the doses being used in accordance with its 
product labelling, as this is not the population that the study drug was approved for. 
1.
In the event that you require narcotic painkillers for severe pain (e.g., following the
accident or in case of a new medical condition) most will have a greatly reduced effect
whilst naltrexone is still being released from Vivitrol and higher doses of high potency
opioids may need to be used or alternative, non-opioid treatments.
2.
Vivitrol injection may cause pain, irritation or inflammation at or near the site of
administration as a result of an allergic response or other inflammatory process.
3.
Known side-effects from naltrexone include difficulty sleeping, anxiety, nervousness,


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6 
abdominal pain/cramps, nausea and/or vomiting, low energy, join and muscle pain, 
headache, loss of appetite, diarrhea, constipation, increased thirst, increased energy, 
depressive mood, irritability, dizziness, skin rash, delayed ejaculation, erection 
dysfunction, reduced sexual desire, and chills. 
4.
Some studies have shown a reversible liver injury indicated by elevated liver enzymes at
naltrexone doses which are much higher than those proposed in this study. At low doses,
similar to those proposed in this study, clinical studies indicate that the risk of liver injury
is low. Therefore, you will be screened for any liver impairment (via routine blood Liver
Function Tests) and if you are found to have levels significantly greater than the normal
range you will not be enrolled into this study. You may be referred to another doctor who
can propose a treatment plan for your elevated liver enzymes.
5.
Naloxone injection may cause withdrawal symptoms in individuals who are opioid
dependent including nausea, vomiting, diarrhea, stomach pain, fever, sweating, body
aches, weakness, running nose, goosebumps, shivering, increased heart rate, and anxiety.
You should not participate in this study if you take opioid (narcotic) painkillers such as
(such as codeine, oxycodone, fentanyl).
6.
(for Females) The procedures of this study are not considered safe during pregnancy or
breast-feeding, because there is concern about Vivitrol/naltrexone causing permanent
damage to a developing fetus or young infant (for example, birth defects, or problems that
emerge during infancy or childhood). Therefore, you should not participate in this research
if you are pregnant, or breast feeding a baby, or if you plan to become pregnant during the
time you are in the study.
7.
A blood pregnancy test will be conducted before you enter the study. If the test is positive,
you will not be able to participate in the study. Pregnancy tests will be repeated monthly
during the study. It is important to understand that even if a pregnancy test is negative, you
could still be pregnant, because these tests cannot detect very early pregnancies (that is,
within the first few days). If you are sexually active, it is very important that you use an
effective form of birth control before and throughout your study participation. Methods of
birth control considered to be effective include: double barrier methods (condom plus
spermicide, or diaphragm plus spermicide), any form of hormonal contraception such as
Depo-Provera, daily oral contraceptive, transdermal patch or NuvaRing, or intra-uterine
devices. It is important to understand that even if you use an effective birth control method,
there is still a chance you could become pregnant. Also, if you do not use the birth control
method consistently (for example if you don’t use condom/spermicide some of the time)
you may become pregnant. If you think you might be pregnant, it is important to let the
study team know right away. The study team will conduct a pregnancy test and help you
decide what to do next.
8.
You will be compensated with a Clincard for your participation in the research study.
If you received over $600, this amount is considered to be income, and therefore may result
in potential tax implications.
9.
Personal expenses may be made when traveling to your study visits. You will be
reimbursed $20 for travel expenses at each visit. If your travel expenses are more than $20,
you may submit receipts for reimbursement up to $50 total for travel.


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10.
During the declared public health emergency, such as the community spread of the novel
coronavirus, there is an increased risk related to the necessary travel to the research clinic
and the visit at the clinic. This may include a risk of getting exposed to the virus and the
risk of getting infected and developing an infection-related disorder (e.g. COVID-19). This
risk can be reduced by taking recommended precautions which include: always wearing a
mask in public and while traveling, practicing hand hygiene especially after being in the
public spaces, and staying at least 6 feet away from others. It is also important that you
remain informed about public health recommendations, such as CDC guidelines and local
government guidelines and directives, and we will also provide you with such updates as
they become available.
11.
If you do not feel comfortable traveling to the research clinic for an appointment, for
example if the subway you would normally take is crowded, you can reschedule, or we may
be able to arrange alternative transportation.
12.
If you are unable to attend scheduled visits because of the restriction on travel we may  not
be able to detect abnormal blood test results in time and your health may be  compromised.
Similarly, if you do not have regular pregnancy tests as directed by the  team you may miss
signs of early pregnancy.
VI.
Withdrawal from the Study
You can withdraw from the study at any time without giving a reason. If you decide to withdraw 
from the study then data collection will cease and there will be no further contact with study site. 
Please be mindful that for a period of 30 days after your last Vivitrol injection there may a risk 
that opioid based medication may have a reduced affect. There is no option to remove Vivitrol. 
In addition, participants may be withdrawn from the study by the investigator for reasons such as: 
adverse event, or any other medical condition (e.g., pregnancy), meeting an exclusion criterion, 
loss to follow-up, or a clinical deterioration.  
VII.
Benefits
There are no direct benefits to you for participating in this study as this was not designed for your 
benefit. This study has been designed to collect information which will be used to help determine 
whether future slow release naltrexone preparations implant should be used as a treatment for 
people with an opioid use disorder, and to help obtain approval from the U.S. Food and Drug 
Administration (FDA).  
VIII.
Confidentiality
Any information collected during this study that can identify you by name will be kept confidential. 
We will do everything we can to keep your data secure, however, complete confidentiality cannot 
be promised. Despite all of our efforts, unanticipated problems, such as a stolen computer may 
occur, although it is highly unlikely. We will do everything we can to keep others from learning 
about your participation in the research.  
To further help us protect your privacy, the investigators will obtain a Confidentiality Certificate 
from the Department of Health and Human Services (DHHS). With this Certificate, the 


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investigators cannot be forced (for example, by court subpoena) to disclose information that may 
identify you in any federal, state, or local civil, criminal, administrative, legislative, or other 
proceedings. Disclosure will be necessary, however, upon request of DHHS for the purpose of 
audit or evaluation. A Certificate of Confidentiality does not prevent you or a member of your 
family from voluntarily releasing information about yourself or your involvement in this research. 
Note however, that if an insurer, employer or other outside party, learns of your participation, and 
obtains your consent to receive research information, then the investigator may not use the 
Certificate of Confidentiality to withhold this information. This means that you and your family 
must also actively protect your own privacy. Finally, the Certificate does not prevent the 
researchers from reporting suspected or known neglect or sexual or physical abuse of a child, or 
threatened violence to self or others. Such information will be reported to the appropriate 
authorities. 
All information will remain confidential so that you will never be identified in any report. All 
research study data related to your information will be de-identified by assigning an alpha-numeric 
code. Your identity will be known only to the investigators, who are bound by strict ethical 
guidelines never to release your name. Your data will definitely not be disclosed to any other 
person outside the study team unless required to do so by law. All records will be stored in locked 
files and will be kept confidential to the extent permitted by law. Any private information or 
biological specimens that are collected as part of this research will not be used for future research 
studies or distributed to another investigator for future research studies, with or without identifiers. 
However, your biological specimens may be used for commercial profit and you will not share in 
this commercial profit. In the event that this occurs, there will be no personal information linking 
you to the data you provided. This study will not include whole genome sequencing.   
Any clinically significant abnormalities detected on the safety laboratory reports or the ECG will 
be communicated to you. 
Records will be available to research staff, and to Federal, State and Institutional regulatory 
personnel (who may review records as part of routine audits). The following individuals and/or 
agencies will be able to look at and copy your research records: 
- 
The investigator, study staff, Columbia University staff, and Clinilabs staff who may be 
evaluating the study or providing services for the study. 
-     Authorities from the New York State Psychiatric Institute, including 
the Institutional Review Board. 
- 
The United States Food and Drug Administration (FDA) 
- 
The manufacturer of the O’Neil Long Acting Naltrexone Implant, Go Medical Industries 
Pty Ltd including persons or organizations working with or owned by the manufacturer. 
- 
The financial sponsor of this study, the National Institute on Drug Abuse (NIDA) 
- 
Other government regulatory agencies (including agencies in other countries) if the 
manufacturer is seeking approval for new products resulting from this research. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site may include a summary of the results. You can search this Web site at any time. 


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IX.
Study Compensation
If you choose to participate in this trial, you will receive a card like a debit card (called a ClinCard), 
and money will be added each day after you have completed your study visit. You will be 
compensated based on the following schedule: 
•
$50 for the screening and the consent visit
•
$200 for each inpatient day (4 days)
•
$50 for each scheduled outpatient visit (23 visits). You will also receive an additional
incremental bonus of $10 for each subsequent visit attended (Visit 1: $50, visit 2:
$50+$10, Visit 3: $50+$20, Visit 4: $50 +$30 …). In case the scheduled visit is missed
the value of the bonus is reset to the starting value of $10. This schedule is designed to
reinforce adherence to all study safety assessments.
•
In addition, you will also receive $20 at each visit for transportation and parking
reimbursement. If your transportation costs exceed $20, you can be reimbursed up to $50
with receipts for travel.
•
If you are asked to return for further follow-up visits, or an unscheduled visit due to
public health emergency then you will receive $50.
The total amount of reimbursement should you attend every scheduled visit is $4,580.  
We are required by law to report earning over $600 to the IRS. If you earn more than $600, your 
social security number and amount earned will be reported, and you will receive the appropriate 
IRS form at the end of the year in which you were paid. Please note the payment for this study 
may affect your eligibility for Medicaid and other city and state support services. No information 
about which study you participated in will be provided to the IRS.  
X. 
   In Case of Injury 
Federal regulations require that we inform participants about our institution's policy with regard 
to compensation and payment for treatment of research-related injuries. 
Taking part in this research study may result in injury or harm to you. In the event of an injury 
resulting from your participation in this study, you should seek appropriate medical care and 
inform the study doctor. In the event of an emergency you should go to an emergency room. 
If you are injured or harmed as a result of participating in the study and receive medical care 
through the New York-Presbyterian Hospital (NYPH), a Columbia doctor, or any other health 
provider, you will be sent a bill for whatever medical care you receive. All or part of your bill may 
be paid by your health insurance. If this medical care is provided by NYPH or by a Columbia 
doctor, the study sponsor and the manufacturer of the implant, Go Medical will pay these providers 
for any reasonable medical expenses to treat your injury. The study sponsor, however, is not 
offering to pay for medical expenses that are covered by your insurance provider or if your injury 
was not caused by the study drug/device or a study procedure. 


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Columbia University and New York-Presbyterian Hospital (NYPH) are not offering to provide 
you the drug/device after the termination of the study or to pay you for pain, worry, lost income, 
the cost of your medical care or non-medical care costs that might occur as a result of your taking 
part in this study. However, you do not waive any of your legal rights in signing this form. 
If you believe that you have sustained an injury as a result of participating in a research study, you 
may contact the Principal Investigator at (646) 774-6155 or (212) 923-1397 so that you can review 
the matter and identify the medical resources that may be available to you. 
Please be aware that: 
1. The New York State Psychiatric Institute, Columbia University and New York Presbyterian
Hospital will furnish that emergency medical care determined to be necessary by the medical
staff of this hospital
2. You will be responsible for the cost of such care, either personally or through your medical
insurance or other form of medical coverage.
3. No monetary compensation for wages lost as a result of injury will be paid to you by the New
York State Psychiatric Institute, Columbia University, Research Foundation for Mental
Hygiene or by New York Presbyterian Hospital.
4. By signing this consent form, you are not waiving any of your legal rights to seek
compensation through the courts.
XI. Questions
If you have any questions relating to your participation in this study now or in the future, the 
investigator will try to answer them to the best of their ability. If applicable, you will be notified 
of significant new findings that may relate to their willingness to continue to participate. 
If you have any questions about your rights as a research participant, want to provide feedback, 
or have a complaint, you may call the NYSPI Institutional Review Board (IRB). An IRB is a 
committee that protects the rights of participants in research studies. You may call the IRB Office 
at (646)774-7155 during regular office hours. 
If you have any medical problems relating to the study, you can contact the medical staff 24 hours 
day on (646) 774 6155. 


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XII.
Documentation of Consent for Screening
I voluntarily agree to participate in the screening for the research study described above. 
Print name: 
 (Participant) 
Signed: 
Date: 
I have discussed the proposed research with this participant including the risks, benefits, and 
alternatives to participation (including the alternative of not participating in the research). The 
participant has had an opportunity to ask questions and in my opinion is capable of freely consenting 
to participate in this research. 
Print name: 
(Person Designated to Obtain Consent) 
Signed: 
Date: 


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XIII.
Documentation of Consent
I voluntarily consent to participate in the study. I have read this consent form which includes 
information about the nature and the purpose of the study, as well as a description of study 
procedures. 
I have discussed the study with the investigator or study staff, have had the opportunity to ask 
questions and have received satisfactory answers. The explanation I have been given has 
mentioned both the possible risks and benefits to participating in the study and the alternatives 
to participation. 
I understand that I am free to not participate in the study or to withdraw at any time. My decision 
to not participate, or to withdraw from the study will not affect my future care or status with this 
investigator. 
Print name: 
Signed: 
Date: 
XIV.
Investigator
I have discussed the proposed research with this participant including the risks, benefits, and alternatives 
to participation (including the alternative of not participating in the research). The participant has had 
an opportunity to ask questions and in my opinion is capable of freely consenting to participate in this 
research. 
Print Investigator name: 
Investigator Signed: 
Date: