Naloxone Auto-injector as a Universal Precaution for Patients With Opioid Use Disorder
Phase: NA
Conditions: Opiate Antagonist Overdose, Opioid-Related Disorders
Sponsor: University of New Mexico

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PROTOCOL TITLE:
Naloxone Auto-injector as a Universal Precaution for Patients with Opioid Substance Use 
Disorder (DSM-V)
PRINCIPAL INVESTIGATOR:
Name: Joanna G. Katzman, M.D.
Department: Neurosurgery
VERSION NUMBER:
Version 5.0
DATE:
9/11/2018
REGULATORY FRAMEWORK:
Please indicate all that apply:
DOD (Department of Defense)
DOE (Department of Energy)
DOJ (Department of Justice)
ED (Department of Education)
EPA (Environmental Protection Agency)
FDA (Food and Drug Administration)
HHS (Department of Health and Human Services)
Other:      
Is this a clinical trial under ICH-GCP E6?   
 Yes   
 No
If yes, please confirm that the research team is familiar with and agrees to comply 
with the investigator requirements cited in ICH-GCP E6.  
 Yes   
 No 
ICH-GCP E6 can be accessed by copying and pasting this URL into your 
browser: http://www.fda.gov/downloads/Drugs/Guidances/ucm073122.pdf

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Table of Contents
1.
Objectives.....................................................................................................................3
2.
Background ..................................................................................................................3
3.
Study Design ................................................................................................................8
4.
Inclusion and Exclusion Criteria ..................................................................................8
5.
Number of Subjects......................................................................................................8
6.
Study Timelines............................................................................................................9
7.
Study Endpoints ...........................................................................................................9
8.
Research Setting...........................................................................................................9
9.
Resources Available...................................................................................................10
10.
Prior Approvals.......................................................................................................10
11.
Multi-Site Research ................................................................................................14
12.
Study Procedures ....................................................................................................14
13.
Data Analysis..........................................................................................................15
14.
Provisions to Monitor the Data to Ensure the Safety of Subjects...........................16
15.
Withdrawal of Subjects...........................................................................................16
16.
Data Management/Confidentiality..........................................................................17
17.
Data and Specimen Banking...................................................................................19
18.
Risks to Subjects.....................................................................................................19
19.
Potential Benefits to Subjects .................................................................................20
20.
Recruitment Methods..............................................................................................20
21.
Provisions to Protect the Privacy Interests of Subjects ..........................................20
22.
Economic Burden to Subjects.................................................................................21
23.
Compensation .........................................................................................................21
24.
Compensation for Research-Related Injury............................................................21
25.
Consent Process......................................................................................................21
26.
Documentation of Consent .....................................................................................21
27.
Study Test Results/Incidental Findings ..................................................................22
28.
Sharing Study Progress or Results with Subjects...................................................22
29.
Inclusion of Vulnerable Populations ......................................................................22
30.
Community-Based Participatory Research.............................................................22
31.
Research Involving American Indian/Native Populations .....................................23
32.
Transnational Research...........................................................................................23
33.
Drugs or Devices ....................................................................................................23
Checklist Section ...............................................................................................................25

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1. Objectives
To conduct a pilot study of a naloxone auto-injector in a “Universal Precaution” manner 
for patients with opioid substance use disorder. Our three objectives are:
1) To decrease the number of fatal and nonfatal overdose deaths by use of the 
naloxone auto-injector by co-prescribing in the University of New Mexico 
Addiction and Substance Abuse Program (UNM ASAP).
2) To study the characteristics of the study subjects who performed the overdose 
reversals (vs. the study subjects who did not) using a biostatistical logistic 
regression analysis
3) To qualitatively study the in-depth characteristics of study subjects who a) 
documented many overdosed reversals/”saved” many community members, b) 
documented one overdose reversal/”saved” one community member, and c) did 
not document any overdose reversals. 
4) Study the 2 mg Evzio autoinjector product to prospectively analyze the 
difference in doses (2 mg vs. 0.4 mg) needed to reverse an overdose. The 
goal will be to recruit 100 patients in one year and document between 20-
30 overdose reversals in the community. 
Note: Between April 4th 2016 and April 4th 2017, 383 study subjects were 
enrolled and there were 93 reported overdose reversals. We are currently 
enrolling new patients at the rate of 6-10 new patients per month.
2. Background
a.
The use of naloxone auto-injectors to block the pharmacological effects of opioid 
medications may have a positive impact on the overdose deaths from prescription opiates 
if utilized in a manner similar to other emergency devices. Several formulations are 
available including intravenous, intramuscular, and subcutaneous injections, all of which 
are commonly used administration routes. Adverse events due to opioid overdose can 
occur in many situations, and risk of death increases if treatment is not administered 
immediately.  Because of respiratory depression, there is not enough time for patient 
transport to the emergency room before treatment is initiated. The risk of death, and/or 
cerebral hypoxia/anoxia increases substantially. A formulation of naloxone that is easy to 
administer under any condition could be utilized as a “rescue kit” in the same conceptual 
manner of “Universal Precautions” as a glucagon injection is used for a person that uses 
insulin to control blood sugar in an emergency.
According to the National Survey on Drug Use and Health, between 55% of patients 
dying of an unintentional opioid overdose obtain their medication from a friend or 
relative.1 17.3% of patients dying of an unintentional opioid overdose obtain their 
medication directly from one doctor. Additionally, unintentional opioid overdoses remain 
the third leading cause of childhood poisonings at 7.9% of all childhood poisonings (after 
cosmetics and cleaning products).2 
b.
Drug Prescription Overdose Death in the United States and New Mexico 
Death due to opioid overdose is a serious issue in the Unites States. The Center 
for Disease Control reports that 14,800 people in the United States died of prescription 
opioid overdose in 2008, more than triple the figure from 1999.5 Additionally, 475,000 

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emergency room visits due to misuse and abuse of prescription opioid were reported in 
2009.5 
Opioid use and related deaths are critical issues in New Mexico. In 2008, New 
Mexico had the highest opioid overdose death rate in the Unites States --27.0 deaths per 
100,000 population, 2.3 times higher than the U.S. average of 11.9 in 2008.5,6 Although 
the death rate was reduced to 21.6 deaths per 100,000 population in 2009, it rose to 23.3 
deaths in 2010 and 25.9 deaths in 2011. Both figures still exceed the U.S. average.7 
Moreover, not only is the opioid death rate high in New Mexico, the overdose death rate 
for the illicit drug heroin is also high. Although the rate per 100,000 population of opioid 
overdose deaths was the worst in 2010 in New Mexico, the rate of prescription painkillers 
sold was 6.7 per 100,000 population, which was not the highest opioid sales rate in the 
United States (highest: Florida, 12.6 per 100,000 population; the US average: 7.3 per 
100,000 population).5 A confounder to this issue is that at this time the national mortality 
data provided by the Centers for Disease Control and the mortality data for New Mexico 
provided by the Office of the Medical Investigator are not able to define if deaths are due 
to illicit opiate use such as heroin, prescribed opiate use or both. This indicates that drug 
overdose deaths may be due to greater misuse of pain medications in New Mexico. 
Furthermore according to the Office of Adolescent Health, 8% of adolescents 
(ages 12-17) in New Mexico used pain relievers, including opioids, for nonmedical 
purposes whereas the U.S. average was 6% in 2011.8 The rate of exposures to tobacco, 
alcohol, and other illicit drugs was also higher in New Mexico than the U.S. average.8 
The availability and use of drugs at an early age may contribute to the reasons why New 
Mexico has one of the highest rates of drug over dose death in the nation.
Although drug overdose death rates varied by county in New Mexico, figures 
from the New Mexico Department of Health (NMDOH) show that the age-adjusted drug 
overdose death rate in New Mexico was 24.1 per 100,000, and illicit drug use and 
prescription drug use were equally contributed to the deaths.7,9 Bernalillo County, where 
the University of New Mexico Hospital study site is located, has the highest population in 
New Mexico (estimated 662,564 in April 2010), and approximately 30% of New 
Mexico’s residents live in Bernalillo County.10 Bernalillo County experienced the 10th  
highest drug overdose death rate (25.4 per 100,000) in New Mexico between 2008 and 
2012.7 This is greater than the U.S. average and the rate of New Mexico. Therefore, 
prevention of drug overdose deaths is a socially and epidemiologically critical issue in 
Bernalillo County, and any interventions for the prevention of drug overdose deaths must 
be established immediately.
 
c.
Use of naloxone in the field to treat opioid overdose

Treatment of Drug Overdose 
The increase in deaths due to opioid overdose has contributed to the development of 
community-based overdose prevention programs, such as Project Lazarus, overdose 
education and naloxone distribution (OEND), and Project DAWN.11-13 Naloxone is 
considered the primary antidote for opioid overdose and is vital in preventing fatal 
events. It is a competitive mu opioid-receptor antagonist that reverses opioid intoxication 
and is given via a parenteral, intranasal, or pulmonary route.14 Naloxone’s onset of action 
is seen in less than two minutes and lasts 20 to 90 minutes.14 Dosing of naloxone is 
empirical, depending on many factors, including the quantity of opioid ingested, relative 

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affinity for the mu opioid-receptor, patient weight, and degree of penetration of the opioid 
into the central nervous system.14 Initially, a 0.04 mg dose of naloxone should be given 
intravenously for respiratory depression and other symptoms associated with opioid 
overdose.14 If the patient does not respond, the dose should be increased every two 
minutes to a maximum of 15 mg.14 For intramuscular or subcutaneous administration, a 
single dose of 0.4 mg is given, and it may repeat every 2 to 3 minutes until emergency 
medical assistance becomes available.14 

Project Lazarus11
Wilkes County, which is in western North Carolina, had a population of 
approximately 66,500 in 2010. Their population was primarily composed of workers who 
historically suffered from chronic pain due to work-related injury. In 2009, the 
unintentional drug overdose death rate in Wilkes County was 46.6 per 100,000 
population, or four times greater than the U.S. average. Thus, reducing unintentional drug 
overdose deaths was critical for Wilkes County. 
The Wilkes County Health Department and the University of North Carolina took the 
initiative to launch a drug overdose prevention study. Its objectives: 

Establish a community-activated drug overdose prevention study and build a 
partnership among healthcare providers.

Monitor data regarding unintentional drug overdose deaths before, during, and 
after the study.

Prevent unintentional drug overdose deaths in the county.

Use a naloxone rescue kit for people at risk of drug overdose deaths. 

Evaluate the project. 
To accomplish these objectives, the research team educated primary-care physicians 
and people who were at risk of drug overdose death. The physicians received training to 
manage patients with chronic pain and to prescribe opioid safely with the naloxone 
rescue kits. The patients received education on pain management and opioids at a 
prescriber’s office and received the naloxone rescue kit for free.
In 2010, the research team significantly reduced the number of unintentional drug 
overdose deaths to 29.0 per 100,000 population. Additionally, the number of drug 
overdose deaths due to prescription opioid was reduced to 10% (2010) from 82% (2008) 
of all drug overdose deaths in Wilkes County.
In only one year, the program was able to successfully reduce the number of 
unintentional drug overdose deaths in Wilkes County. The education for primary-care 
physicians and for high-risk patients of drug overdose deaths, along with the naloxone 
rescue kit, contributed to the dramatic changes. 

Overdose education and nasal naloxone distribution (OEND) program in 
Massachusetts12
The OEND program is also well-known clinical study that successfully decreased 
drug overdose deaths in Massachusetts. The Massachusetts Department of Public Health 
took the initiative for the study, the objective of which was to investigate the education of 
drug overdoses for people at high risk of drug overdose death and for bystanders (defined 
as “social service agency stuff, family and friends of opioid users”). The investigators 

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monitored the rate of drug overdose deaths and acute care utilization (e.g., emergency 
room visit) in Massachusetts.
The study recruitment was held in 351 communities in Massachusetts between 2006 
and 2009. Nineteen communities, which reported five or more drug overdose deaths 
annually between 2004 and 2006, were targeted to initiate interventions for drug 
overdose. Study participants were opioid users (defined as current use or at recovery 
stage) who were at risk for drug overdose and their bystanders. The investigators 
provided education on drug overdose and on management of drug overdoses to patients 
who were opioid users and their bystanders. The education was a modified version of the 
Harm Reduction Coalition and the Chicago Recovery Alliance, and participants learned 
current circumstances of drug abuse, risk reduction of drug overdose deaths, emergency 
rescue breathing, and administration of intranasal naloxone. The rescue kits were 
distributed to all study participants. The naloxone rescue kits were dispensed to 2,912 
people. The kits were used in 327 times, and opioid users used 286 unique individuals 
(87.5%). 
Overall, naloxone was effective in improving unresponsiveness and respiratory 
depression. The success rate was 98% (opioid users: 98%; bystanders: 100%), and one or 
two doses of naloxone did rescue patients with unresponsiveness and respiratory 
depression. Among all study participants who used the naloxone rescue kit, 95% used it 
for someone other than themselves, such as friends, partner or family, or strangers. 
Among opioid users, only 6% used the rescue kit for themselves. Among bystanders, 
43% used the rescue kit for friends, 41% for partners or family, and 16% for strangers. 
The results of this study illustrate that availability of the naloxone rescue kits saved 
not only people at risk of opioid overdose death but also their friends, family members, or 
strangers whose risk of opioid overdose death was unidentified. Additionally, the higher 
the study enrollment rate, the more effective the rescue kit was in preventing drug 
overdose deaths.
 

Similar studies with naloxone in New Mexico (studies in Taos, Roswell, and 
Santa Fe)15 
In New Mexico, the NMDOH conducted a similar pilot study with naloxone for the 
prevention of drug overdose deaths in the Taos, Roswell, and Santa Fe areas. The pilot 
study started in January 2013, and the investigators monitored the following items at 
enrollment to determine which risk factors a study candidate had for drug overdose 
deaths among opioids and other illicit drug users, such as history of substance abuse, 
diagnosis of psychiatric diseases, concurrent liver, kidney, and/or respiratory disease(s), 
high daily dose of opioids.
The investigators also assessed reasons for the use of a naloxone rescue kit (overdose, 
outdated, lost, stolen, or destroyed); who the kit was used for (person who is prescribed 
opioid or not); other medications (heroin, cocaine, benzodiazepine, alcohol, “meth”); 
utilization of healthcare providers/institutions; and utilization of emergency call. 
The NMDOH reported that the investigators in three areas have continued 
recruitment of study candidates. 
Innovation of Proposed Study
Currently, a significant amount of attention is being directed to the use of COT. Given 

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that New Mexico ranks third in the United States for the rate of accidental overdose 
deaths associated with prescribed opioid use, this attention is warranted. Prescribing 
intramuscular and intranasal naloxone rescue kits to high risk patients receiving chronic 
opioids to treat chronic pain has been employed recently as one effort that might decrease 
the accidental overdose rate associated with these medications. In past studies, risk 
stratification criteria have been employed to select patients on chronic opioid therapy 
who may benefit most from the use of an intramuscular or intranasal naloxone rescue kit. 
This method could inadvertently exclude patients who also may benefit from this therapy. 
Patients who do not fit the current definition of high risk criteria, such as anyone on 
chronic opioid therapy with comorbid dementia who forgets they already have taken their 
opioid mediation and the takes a second dose, or a patient whose metabolism of an opioid 
is changing, still may be at risk for adverse events associated with chronic opioid therapy. 
Rather than using inclusion criteria to select patients who receive naloxone auto-injector, 
a model that does not define “high risk” patients a priori, may offer improved benefits 
from the use of naloxone auto-injector. If a “universal precautions” method is employed, 
much in the same manner as epinephrine injection dispensed to patients with a history of 
anaphylaxis, or a glucagon pen and/or glucose tablets being dispensed to patients who use 
insulin to treat diabetes, the prescribing of naloxone auto-injector to all patients on 
chronic opioid therapy for chronic pain may have a greater impact on the accidental 
overdose morbidity/mortality rate associated with the use of chronic opioid therapy. 
Additionally, it may be beneficial to make naloxone available as a universal precaution 
for people who were not prescribed opioid to decrease mortality due to drug overdose. 
According to previous naloxone studies, a significant amount of opioid mortality occurs 
among those for who the opioid wasn’t prescribed.11,12
Year 1- ASAP Study
Since April 2016, we have enrolled 358 patients at ASAP in our prospective 
nonrandomized clinical trial using the Evzio autoinjector. We have documented 82 
overdose reversals thus far. Only one of the reported overdose reversals was from the 
study patients at ASAP, while the other 81 overdose reversals were from community 
members received naloxone from the study patients. For every 100 patients enrolled in 
the study, approximately 23 overdose reversals have been reported. We have submitted a 
peer-reviewed article about this data, and are now waiting to hear back regarding 
acceptance of the submission. 
3. Study Design
3.1. The previous study at ASAP is a prospective observational study using the 
naloxone 0.4 mg auto-injector which took place April 4th, 2016 through April 
30th, 2017.
3.2. Evaluation of patients enrolled include: # overdoses reversed, # naloxone doses 
needed, urine toxicology, history of overdoses witnessed, history of being 
reversed by naloxone, demographic information, medical history, etc. 
3.3. For this current study, we propose the following new additional studies:
A biostatistical logistic regression analysis to study the characteristics of 
the study subjects who performed the overdose reversals (vs. the study 
subjects who did not).

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A qualitative study to examine in-depth the characteristics of study 
subjects who a) documented many overdosed reversals/”saved” many 
community members, b) documented one overdose reversal/”saved” one 
community member, and c) did not document any overdose reversals
Study the 2 mg Evzio autoinjector product to prospectively analyze 
the difference in doses (2 mg vs. 0.4 mg) needed to reverse an 
overdose. The goal will be to recruit 100 patients in one year and 
document between 20-30 overdose reversals in the community. 
4. Inclusion and Exclusion Criteria
Inclusion Criteria
A. All patients treated with naltrexone, methadone or buprenorphine as 
medication assisted treatment at the UNM Addiction and Substance Abuse 
Program (UNM ASAP) aged 18 or older.

Over 70% of patients at UNM ASAP on medication assisted treatment use 
methadone
B. Subjects who sign a consent form.
Exclusion Criteria
A. Subjects who are allergic to naloxone and its inactive ingredients. 

Inactive ingredients: buffering agents
B. Subject younger than 18. 
5. Number of Subjects
The University of New Mexico Addiction and Substance Abuse Program (UNM 
ASAP) will be the research site, to include all subjects with a DSM-V diagnosis of 
substance use disorder. The UNM ASAP treats approximately 600 patients for 
substance use disorders with diagnosis of opioid dependence disorder annually. 
Ninety percent of these patients are treated daily as a part of their federally funded 
methadone maintenance treatment program. The remainder are treated with 
buprenorphine or naltrexone as opioid replacement therapy. Naltrexone has an FDA 
indication to treat opioid dependence.
We will explain the study to all potential candidates; however, 20-30% of the patients 
may decline to participate in the study. 
We are enrolling study subjects at a current rate of approximately 6-10 subjects per 
month and anticipate this continuing throughout the year. Additionally, we can 
anticipate that our current study population is reporting a steady overdose reversal 
rate of 23% for every 100 patients enrolled. This number has not changed since July 
2016. 
Power analysis: the occurrence of opioid overdose death at the UNM ASAP is 
approximately 10% annually. With a sample size of 500 people we will have 80% 
power to detect a 20% difference in mortality at alpha level of 0.05. 
6. Study Timelines

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The research team submitted the initial IRB application at the beginning of October 
2015. Recruitment at UNM ASAP will start in January 2016, after receiving IRB 
approval. The research team will follow the study subjects for one year and will close 
the study when qualitative interviews have been completed. 
If the IIS is approved, the research team will begin the logistic regression analysis as 
soon as possible. Once the IRB approves the qualitative modifications, the face-to-
face 1:1 interviews will begin with the study subjects.  
The recruitment for the Second Year Study will begin June 1, 2017 at UNM ASAP, 
after receiving IRB approval for protocol amendment. The research team will follow 
a study subject for one year and will close the study when qualitative interviews have 
been completed. 
7. Study Endpoints
There are four endpoints in this study:
1. Number of fatal over dose deaths and near fatal overdoses averted by use of 
naloxone auto-injector co-prescribing from the University of New Mexico 
Addiction and Substance Abuse Program (UNM ASAP)
2. To study the characteristics of the study subjects who performed the overdose 
reversals (vs. the study subjects who did not) using a logistic regression analysis
3. To qualitatively study the in-depth characteristics of study subjects who a) 
documented many overdosed reversals/”saved” many community members, b) 
documented one overdose reversal/”saved” one community member, and c) did 
not document any overdose reversals
4. Study the 2 mg Evzio autoinjector product to prospectively analyze the 
difference in doses (2 mg vs. 0.4 mg) needed to reverse an overdose. The 
goal will be to recruit 100 patients in one year and document between 20-
30 overdose reversals in the community. (Between April 4th 2016 and 
April 4th 2017, 383 study subjects were enrolled and there were 93 
reported overdose reversals)We are currently enrolling new patients at the 
rate of 6-10 new patients per month.
8. Research Setting
Research facility: The study is conducted at UNM ASAP.  
UNM’s ASAP is a part of the behavioral health program under the UNM Psychiatric 
Center. ASAP specializes in providing diverse, proven substance abuse and mental health 
treatment, including specialized services for women. ASAP provides services to adults 
and adolescents with a primary substance abuse diagnosis and/or individuals who have a 
substance abuse disorder along with other mental health issues.
Location: 2600 Yale SE, Albuquerque, NM 87106
9. Resources Available
Study personnel
Principal investigator: 
Joanna G. Katzman MD, professor, Department of Neurosurgery, School of Medicine
As medical director and founder of the UNM Pain Center and ECHO Pain clinic at the 

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University of New Mexico, Dr. Joanna G. Katzman has played key roles in improving 
access to specialty care for chronic pain patients, as well as in improving the quality of 
care by providing consultative, educational, and therapeutic services to patients 
throughout New Mexico. She has a broad background in neurology, pain and headache 
management, neurorehabilitation, and traumatic brain injury, and for the past three years 
she has effectively led the interdisciplinary team of pain specialist at Project ECHO. She 
will serve as an investigator on this project. This proposed project is a collaboration study 
with the New Mexico Department of Health and will definitely reduce drug overdose 
deaths, which are a serious public health issue in New Mexico.
Co-investigators (alphabetical order)
Snehal Bhatt, MD, associate professor, Addiction and Substance Abuse Program 
Medical Director, School of Medicine
Snehal Bhatt is a board certified physician in General Psychiatry and Addiction 
Psychiatry.  He is on faculty at the University of Mexico, where he is the medical director 
for the Addictions and Substance Abuse Programs, which is a clinic serving over 800 
patients with addictions, and co-occurring psychiatric illnesses.   Additionally, he has 
been partnering with IHS Center for Telebehavioral Excellence and tribal programs to 
provide direct care, along with didactics and case consultations to clinicians across the 
nation.  His current research projects include working with prisoners prior to their release 
in order to reduce recidivism rates, and studying the effects of psilocybin assisted 
psychotherapy as a treatment for alcoholism.  His professional areas of interest include 
improving access to addictions treatment, managing co-occurring pain and addictive 
illnesses, teaching, and sociocultural elements of addictive illnesses and treatment.
Nina Greenberg, MS, Senior Lecturer, Department of Mathematics and Statistics, 
University of New Mexico
Nina Greenberg’s primary responsibility is as a Senior Lecturer in Statistics at the 
University of New Mexico. As UNM’s Department of Mathematics and Statistics 
Undergraduate Introductory Statistics (Stat145) course coordinator since 2009, Nina 
supervises about 30 sections of Introductory Statistics, with approximately 55 
undergraduate students in each section, taught by a mixture of graduate teaching 
assistants and adjunct faculty. Nina has completed her course work towards her Master’s 
in Public Health from UNM, she is on track to receive her degree this summer after 
completion of her professional paper which will analyze factors associated with years of 
potential life lost and malignant breast cancer. In addition to an MA in Statistics from 
UNM (2006), she has earned a Secondary Teacher Certificate from the University of 
Phoenix (2002), an MS in Marine Science from San Jose State (1992), a BA in Biology 
and a BS in Journalism from the University of Colorado (1985). Since August of 2016, 
Nina has served as a part-time Biostatistician for Project ECHO (Extension for 
Community Healthcare Outcomes) working to evaluate a medical provider virtual 
intervention for training in pain management within the U.S. Defense Health Agency. 
She recently conducted data analyses for a study on the co-prescribing of Naloxone to 
patients receiving medication assisted treatment. Nina has worked with the Indian Health 

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Services analyzing population demographics as well as differences in pre-and post-survey 
data from national virtual trainings for health care providers in pain and addiction. She 
has also conducted data analyses on associations between physical activity and grades in 
the NM-YRRS survey of adolescents in New Mexico.
Julie Griffin Salvador, PhD, Assistant Professor in the University of New Mexico, 
Department of Psychiatry, Division (UNM) of Community Behavioral Health (CBH).
As a trained cultural anthropologist, she focuses on use of qualitative data and 
ethnographic methods in her community engaged research approach, working in 
partnership with rural and underserved populations in New Mexico including American 
Indian and Hispanic communities. She has extensive experience conducting federally 
supported research studies, serving as lead researcher responsible for study design, 
proposal development, implementation, and dissemination activities. Her research 
projects include funding from the National Institute on Drug Abuse, the Substance Abuse 
and Mental Health Services Administration, and multiple research contracts with New 
Mexico’s Behavioral Health Services Division and with the Children Youth and Families 
Department. Her recently completed research projects have focused on efforts to expand 
access to evidence-based practices for rural primary care and behavioral health care 
providers. She has enrolled over 300 rural providers across the state in data collection 
efforts to understand barriers to and solutions for improving best practice 
implementation. Currently, Dr. Salvador leads the SAMSHA funded Systems of Care 
Expansion initiative focused on improving care for youth in New Mexico with Serious 
Emotional Disturbances and their families. Dr. Salvador has broad research interests 
within health and health services including teen pregnancy, diabetes and behavioral 
health, particularly substance abuse, with a qualitative, ethnographic approach to 
understand and improve health outcomes and health disparities. She is interested in 
understanding the feasibility and impact of televideo approaches for building provider 
capacity to implement evidence-based practices in behavioral health in rural and high 
need areas. Her research focuses on health services at multiple levels including 
consumers, direct service providers, state-level leadership and policy makers to improve 
our understanding of individual, community, systems and policy level factors that impact 
health disparities in rural and ethnically diverse communities.
Kimberly Page, PhD, Professor and Chief of Epidemiology, Biostatistics and Preventive 
Medicine, in the Department of Internal Medicine at UNM HSC.
Dr. Kimberly Page is an infectious disease epidemiologist with experience in prospective 
cohort studies, clinical trials and implementation science. She is a Professor and Chief of 
Epidemiology, Biostatistics and Preventive Medicine, in the Department of Internal 
Medicine at UNM HSC. Dr. Page’s leads nationally and internationally recognized 
research on HIV and viral hepatitis prevention in underserved and vulnerable 
populations, including people who inject drugs (PWID), and women engaged in 
transactional sex.  She likes to say that her ‘laboratory’ is in the community, and 
embraces the challenges of working with hard-to-reach populations with her work in the 
U.S. and internationally.  In addition to leading the country’s first trial testing a 
prophylactic HCV vaccine in PWID, she has launched new studies integrating HCV 

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treatment and prevention in rural and urban New Mexico.  She collaborates with leading 
researchers in the U.S and other countries to better understand and deliver global health 
knowledge and HIV and HCV prevention and to improve health in underserved 
populations.  Dr. Page has a combined nine years of experience as an IRB member, 
including two years at UNM and previously as a faculty member at two other institutions 
Mikiko Y. Takeda, MS, Pharm.D., assistant professor, Department of Pharmacy 
Practice and Administrative Sciences, College of Pharmacy
Dr. Takeda is a clinical assistant professor of pharmacy practice focusing on neurological 
diseases, especially epilepsy and pain. Her current educational program in clinical 
research and public health at the University of Kansas Medical Center strengthened her 
research skills. She also has a research background in Japan, where she received a 
master’s degree in pharmaceutical science, evaluating the effects of preservatives in eye 
drops on a rabbit cornea using electrophysiological methodology. She also initiated a 
cross-sectional study of disinfectant use at Saga National Hospital as a principal 
investigator to enhance appropriate disinfectant use in the hospital. As part of her 
fellowship, she initiated a safety study of Keishibukuryogan (a Japanese herbal 
medication) among women with epilepsy. Her passion and enthusiasm for clinical 
research motivates her to carry out the proposed study. She coordinates this clinical study 
and prepares necessary documents, including the research proposal, informed consent 
form, and budget sheet. She also analyzes and summarizes the data with SAS. 
Other significant study personnel/contributor (alphabetical order)
Amal Alchbli, M.D., Department of Neurosurgery
Role: Research assistant
Monica Moya, M.S., Department of Neurosurgery
Role: Research assistant
Karla Wagner, PhD, Assistant Professor in the School of Community Health Sciences 
at the University of Nevada, Reno.
Dr. Wagner is an Assistant Professor in the School of Community Health Sciences at the 
University of Nevada, Reno. She conducts mixed methods research that focuses on the 
prevention of negative health outcomes associated with injection drug use, especially 
HIV, viral hepatitis, and fatal overdose. Her current projects use qualitative, quantitative, 
and social network methods to investigate the social and environmental factors associated 
with HIV risk, HIV testing, and drug overdose. She also provides technical assistance and 
conducts evaluation research on the effectiveness of overdose education and naloxone 
distribution to prevent fatal opioid overdoses. 
Students
10.Prior Approvals
Similar study using intranasal naloxone for patients with chronic opioid therapy at the 
UNM Pain Center (IRB study ID: 13-630). It was approved in April 2014 (current study 
status: continued) (see Appendix 1 – initial approval letter).

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11.Multi-Site Research
The study site is UNM ASAP only. 
12.Study Procedures 
Investigators at UNM ASAP will distribute naloxone rescue kits to all study subjects. 
Naloxone is a prescription medication administered intravenously, subcutaneously or 
intramuscularly. In this study, the research team will use the naloxone auto-injector 
which is the only product FDA approved and labeled for use by family members or 
caregivers for emergency therapy wherever opioids are present. The research team will 
distribute the kits at the initial visit and provide education on drug overdose and rescue 
method from an overdose (education materials: see Appendix 2: A Patient’s Guide to 
Evzio and Appendix 9: Opioid Overdose Toolkit) upon receiving informed consent. The 
education material covers education on opioid overdose and how to use the auto-injector.  
Education will be provided not only for patients but also, if the patient agrees, their 
bystander (bystander is defined as a caregiver, such as family member, friend, etc.) at 
initial visit and follow-up visits. According to the New Mexico Good Samaritan Law, any 
bystanders of patient are able to provide naloxone when drug overdose occurs. Thus, we 
will educate patients and their bystanders on the signs and symptoms of drug overdose 
due to opioids, drug overdose deaths and its risks (Appendix 9), how to use naloxone 
auto-injector (Appendix 2).  If the patient would like to be enrolled in the study without a 
bystander present, he/she will be educated on the use of intramuscular naloxone and 
asked that they educate their friends and/or family. The subjects will return to UNM 
ASAP every three months after the initial visit for a follow-up. The following figure 
describes the procedures the investigator will carry out during each visit.
Initial Visit: Assess inclusion/exclusion criteria, obtain consent, results of urine drug 
screening test, and baseline information, provide face to face opioid education (individual 
or group education – up to 6 people in a group) and how to use naloxone auto-injector, 
and distribute one naloxone auto-injector carton prior to the next study visit (there are 2 
Initial visit
Assess
Inclusion/exclusion criteria
Obtain
Consent
Patient baseline information
Results of urine drug screen test
Provide
Face-to-face education on opioid 
overdose 
Education on how to use naloxone 
rescue kit
Distribute
Naloxone rescue kits
Follow-up visits 
(every three months)
Obtain
Results of urine drug screen test
Monitor
Frequency of naloxone rescue kit 
use 
Reasons for the rescue kit use
Provide
Face-to-face education, as needed
Refill
Naloxone rescue kit, if needed 
Month 12
Obtain
Results of urine drug 
screen test
Monitor
Frequency of naloxone 
rescue kit use 
Reasons for rescue kit 
use
End 
of 
study

14
[Type text]
naloxone auto-injector per carton).
Follow-up Visit (every three months): Obtain results of urine drug screening test, 
monitor frequency of naloxone auto-injector use, reason for naloxone auto-injector use, 
provide face to face education, as needed and refill naloxone auto-injector kit as needed.
When patients report opioid overdose at these follow-up visits, we will obtain further 
information on the overdose via patient interview. The information will include date, 
time, and dose of naloxone use, clinical outcome [i.e., successful opioid reversal, death, 
and utilization of healthcare institution (e.g., EMS, emergency room, hospitalization)], to 
whom the kits were used, causality [i.e., type(s) of opioid], and call 911 after utilization 
of the kit. We will confirm the record by accessing PowerChart, only if patients used 
UNM Hospital for treatment.  
Month 12 (1 Year): End of study visit: Obtain results of urine drug screening test, 
continue to ask same questions as in Follow-up visit.
If a patient uses the naloxone prior to the scheduled clinic visit, the study team will 
distribute one naloxone auto-injector carton prior to the next study visit. The study team 
will inquire about the circumstances for the use of the naloxone auto-injector.
Optional qualitative sub-study: If a study subject is selected as a potential candidate for 
the qualitative study, they may be contacted by phone or in person during one of their 
clinic visits and have the optional sub-study consent explained to them.  If the person 
agrees to be interviewed, this will be done at a private consult room at ASAP. This visit 
may take 30-45 min at the end of which they will receive a $20 gift card.
13.Data Analysis
Statistical Analysis
Statistical analysis will be performed usingSTATA (College Station Texas) and SAS 
version 9.3 (Cary, NC, United States). 
The research team will collect the data and will use a descriptive analysis for 
demographic, social status, medical history, physical examinations, including vital signs 
(normal vs. abnormal findings), number of concomitant medications, scores of 
RIOSORD, and outcome related parameters listed in Section 12. 
The team will compare the monitoring parameters listed above to identify demographic 
data, epidemiological data, and correlations with the use of naloxone rescue kits. 
Differences between ASAP in categorical variables (utilization of naloxone auto-injector, 
utilization of EMX-run and emergency room visit during study period, gender, race, 
ethnicity, education level, marital status, results of physical examination [normal vs. 
abnormal], presence of substance abuse) will be tested by Chi Square test or Fisher exact 
test where appropriate. Differences in continuous variables (e.g., age, RIOSORD scores) 
will be tested by independent two samples, Student’s t test, or Wilcoxon Rank Sum test, 
where appropriate. P values of less than 0.05 were considered statistically significant. 
14.Provisions to Monitor the Data to Ensure the Safety of Subjects

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In accordance with the IRB at UNM HSC, the investigators commit that the data will be 
used only for the research purpose. The data will be disclosed to all study investigators. 
The investigators will use PowerChart to obtain necessary information, such as past 
medical history, family history, and concomitant medications. The investigator will keep 
a patient log (“log book”, Appendix 7) to track patients’ consequent clinic visits. The 
investigators will use paper- and electronic-based data collection during their face-to-face 
interviews. All data will be transferred to REDCap system. The paper-based data and the 
log book will be stored in a locked cabinet in physician’s office (Dr. Bhatt) at UNM 
ASAP. The paper- and electronic-based database and Excel file will be destroyed upon 
completion of data analysis. The study medication is stored in another locked cabinet of 
the same office. This room is also locked and only a few employees (charge nurse, study 
coordinator, PI, medical director) have access to open the room each day.
Reported adverse reactions from naloxone for opioid overdose were tremor and 
hyperventilation associated with an abrupt return to consciousness.16  We will ask if study 
subjects experience withdrawal symptoms at their clinic visits. The frequency of these 
adverse reactions is unknown. These adverse reactions are not life-threatening, and 
hyperventilation will be managed with rescue breathing. This topic is included in 
patients’ education in this study.
Only deidentified health related information will be shared with the study sponsor. 
However, the following agencies will be contacted for specific circumstances: CYFD for 
child abuse; NM Department of Health for reportable communicable disease (e.g., 
measles, varicella, rubella); and UNM security or Albuquerque Police Department for 
subject’s threat of violence to self or others. The study related data may be audited by 
federal agencies, such as the U.S. Department of Health & Human Services or the Food 
and Drug Administration (FDA). You have a right to request in writing the disclosure of 
any identifying information.
Data Safety Monitoring Board Meeting
The study team has periodical Data Safety Monitoring Board meeting. We plan to have 
this meeting every three months to objectively monitor unanticipated problems related to 
the study. When an unexpected adverse reaction is identified, we will schedule a meeting 
immediately. The board members are: 

Edwin M Nemoto, PhD, FAHA, Research Professor, Dir. Research, Department 
of Neurosurgery

William E. Rivers, D.O., Assistant Professor, Department of Neurosurgery

Andrew P Carlson, M.D., Assistant Professor, Department of Neurosurgery
15.Withdrawal of Subjects
Any subject can withdraw from this clinical study at any time during the study period. 
The investigators will explain the withdrawal opportunity before a study subject signs the 
consent form. The investigators may ask the reason for the withdrawal.  
16.Data Management/Confidentiality
Monitoring Parameters

16
[Type text]
1. Outcome related parameters (Appendix 3, 4; self-report).
a.
Number of naloxone auto-injector dispensed.
b. Reason for dispensing the naloxone rescue kit.
c.
Circumstances surrounding the use of the naloxone rescue kit.
o
Including use of other substances such as heroin, cocaine, 
benzodiazepine, alcohol, or methamphetamine/amphetamine.
d. Opiate reversals.
e.
Opioid prescription data through Prescription Monitoring Program (or 
PMP; available through New Mexico State Board of Pharmacy) and actual 
patient’s opioid use
2. Demographic (at initial visit only, Appendix 3: National Institute of Neurological 
Disorders and Stroke [NINDS] data collection format, modified).17 
a.
Age.
b. Gender.
c.
Ethnicity and race (self, maternal, paternal).
d. County of residence
3. Social status (at initial visit only, Appendix 3: NINDS data collection format, 
modified).17
a.
Education level.
b. Marital status.
4. Medical history (at initial visit only, Appendix 3: NINDS data collection format, 
modified).17

Past and current medical history.
5. Behavioral history (at initial visit only, Appendix 3: NINDS data collection 
format, modified).17

Smoking, alcohol, and illicit drug use
6. Family history (at initial visit only).17 

Will only ask addiction-related diseases (i.e., history of alcohol abuse, 
substance abuse [prescription drug and illicit drug], and tobacco use)
7. Vital signs (heart rate, blood pressure, respiratory rate, temperature, weight, 
height, Likert Pain Scale (0-10), Appendix 3, 4: NINDS data collection format, 
modified).17
8. Concomitant medications (Appendix 3: NINDS data collection format, 
modified).17
9. Urine toxicology screening test

Patients have urine toxicology screening test at each clinic visit (every 
week or every 2 or 3 months, which is dependent on patient’s treatment 
regimen), as urine toxicology screening test is a part of standard care at 
UNM ASAP. If a patient does not have urine toxicology screening test 
done within 1 week prior to follow-up study visit, the research team will 
order the test.
10. Risk index for overdose or serious opioid-induced respiratory depression 
(RIOSORD,20 Appendix 5)
Certificate of Confidentiality
This study has a certificate of confidentiality issued by the NIH that protects study 

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subject’s privacy. 
Location of data storage
All paper-based study data will be kept in a locked cabinet at UNM ASAP. Electronic 
data will be kept in a secured computer system in Dr. Takeda’s office (UNM College of 
Pharmacy, Room B21B) and Dr. Joanna Katzman’s office (Clinical Neuroscience Center 
or CNC). The computers are in their personal office behind a locked door, and the 
computer requires a password to open. The password for the office computer will not be 
shared with other people; thus, the data will be safely stored in PI’s office at CNC and 
UNMCOP. Access to study databases is restricted to an as-needed basis. The 
investigators will use paper-based and electronic-based data collection when seeing the 
study subjects.
Duration of data storage
The data will be kept safely for 5 years, at which time Dr. Bhatt at ASAP will destroy all 
paper-based patient-relevant information with a shredder or put it in a confidential 
disposal box. The electronic data will be destroyed at the completion of data analysis.
Data access
Dr. Takeda, Ms Moya and Ms Greenberg will be responsible for data storage and will 
share the data with other IRB-approved investigators on an as needed basis. Dr. Takeda 
and Ms. Moya may share the data with a biostatistician at the Clinical Translational 
Science Center for the purpose of data analysis. The biostatistician will follow HIPAA 
regulations and keep the data in accordance with the data storage policy at CTSC.
17.Data and Specimen Banking
In accordance with the IRB at the UNM Health Science Center (UNM HSC), the 
investigators commit that the data will be used only for the research purpose and not to 
identify individual study subjects. The investigators will use minimum identifiers (e.g., 
date of birth, last clinic visit) to protect the identity of the participants.  
18.Risks to Subjects
The research team assumes the following risks during the study: adverse reactions from 
naloxone and loss of confidentiality.
1. Adverse reactions from naloxone
Reported adverse reactions from naloxone for opioid overdose were tremor and 
hyperventilation associated with an abrupt return to consciousness.16 According to the 
package insert, the abrupt reversal was described as follows: “Abrupt reversal of opioid 
effects in persons who were physically dependent on opioids has precipitated signs and 
symptoms of opioid withdrawal including: body aches, fever, sweating, runny nose, 
sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, 
restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased 
blood pressure, tachycardia.” The frequency of these adverse reactions is unknown. 
These adverse reactions are not life-threatening, and hyperventilation will be managed 

18
[Type text]
with rescue breathing. This topic is included in patients’ education in this study. 
The research coordinator and clinician will discuss the signs and symptoms of a near fatal 
overdose (slowed breathing, pallor, lack of responsiveness, inability to follow directions, 
etc). We provide validated materials to the patients from kaléo (Appendix 2) and 
Substance Abuse and Mental Health Services Administration (Appendix 9) related to 
opioid overdose which they can take home and study as well.  A “practice” naloxone 
autoinjector is then used in the clinic so that the patient and his/her bystander can 
understand how it might be used in an emergency and life threatening situation. In the 
event of emergency Naloxone use, the autoinjector speaks to the patient through the 
procedure so it can help with the delivery of the medication.
Distribution of the naloxone rescue kits and providing appropriate education on drug 
overdoses will potentially save lives of patients in New Mexico who took opioids. 
Naloxone auto-injector enables patients and their bystanders to provide naloxone 
immediately without the utilization of healthcare institution for the administration of 
intravenous naloxone. Additionally, the intramuscular administration route is an easy and 
effective way to deliver medication with minimum drug degradation.
2. Loss of confidentiality
The research team will make efforts to protect patient-related information as 
much as possible. The research team collects patient information, such as demographic 
information, use of opioids, and use of illegal drugs. The research team will not use a 
patient’s name or any information that might reveal the identity of the patient. The 
research team will create a specific ID (i.e., first letter of study site, enrollment number 
(3-digit); e.g., A001) for each patient to minimize using a patient’s name.
Additionally, as stated in Section 26, all paper-based study data will be kept in a locked 
cabinet at UNM ASAP. Electronic data will be kept in a secured computer system in Dr. 
Takeda’s office (UNM College of Pharmacy, Room B21B) and Dr. Joanna Kaztman’s 
office (Clinical Neuroscience Center). 
The team will handle sensitive information regarding illegal drug use of a patient and 
of his/her bystanders. The study team wants to emphasize that the information obtained 
for the study will not be reported to law enforcement authorities. The Certificate of 
Confidentiality, which insures patient’s privacy, was issued by the National Institute of 
Health  for UNM Pain Center and UNM ASAP. 
19.Potential Benefits to Subjects
Because New Mexico has led the country in unintentional opioid overdose deaths 
and opioid misuse, finding appropriate prevention for drug overdose is critical. 
Distribution of the naloxone rescue kits and providing appropriate education on drug 
overdoses will potentially save lives of patients in New Mexico who now have an opioid 
substance use disorder. Intramuscular naloxone enables patients and their bystanders to 
provide naloxone immediately without the utilization of healthcare institution for the 
administration of intravenous naloxone. Additionally, the intramuscular administration 
route is an easy and effective way to deliver medication through the muscle with 
minimum drug degradation. Moreover, appropriate education will help study subjects 
identify symptoms of drug overdose and will manage associated symptoms, such as 
rescue breathing. In our patient education, we will emphasize that naloxone is to be used 

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for opioid overdose as an antidote for patients with chronic opioid therapy but not to be 
used as a means of rescue method for recreational opioid use.
By utilizing a “Universal Precautions” approach in this study, where any patient 
on chronic opioid therapy is given an intramuscular naloxone kit, the stigma attached to 
the use of intramuscular naloxone may be diminished. Additionally, this approach may 
have an impact on the prescribing of chronic opiate medication, to the point that any 
patient being prescribed chronic opiate medications will routinely be given a naloxone 
auto-injector --Much the same as any patient prescribed insulin receives glucose tablets 
and/or a glucagon pen. This would have the potential to dramatically increase the safety 
when opiate medications are misused.
20.Recruitment Methods
Study recruitment will occur at UNM ASAP. Healthcare providers at the UNM 
ASAP will identify a potential study candidate or naloxone posters will be posted in the 
private methadone dispensing room and in the patient rooms. The patient can ask ASAP 
staff in a private setting about obtaining naloxone autoinjectors The candidates will be 
asked by ASAP staff if they are interested in taking part in the study, then they will be 
referred to a study coordinator on the team. The study coordinator will explain the 
clinical study and answer questions, such as about risks and benefits from the study 
candidates. After the candidate understands the study and agrees to sign an informed 
consent form, the candidate becomes a study subject and receives naloxone rescue kits.
21.Provisions to Protect the Privacy Interests of Subjects
Subjects will be notified by their clinic providers of this clinical study. Then the 
provider will obtain patients’ consent. Patient’s personal information will be obtained via 
PowerChart and/or interview, and pharmacy students and pharmacy residents will 
transfer the data to Excel spread sheet, which is stored in a shared drive. Any information 
on study subjects, such as demographic information and history of drug abuse, will be 
confidential. 
A subject will be able to call his/her provider and ask any study-related questions 
before, during, and after the clinical study. The investigators will never start the study if a 
subject has any concerns about the study. A patient’s provider will discuss with an 
investigator or subject’s physician as needed any issues related to a subjects’ health 
condition. 
22.Economic Burden to Subjects
No cost is needed for all study participants for naloxone rescue kits and clinic 
visit for the study purpose. 
23.Compensation
We will provide a $20 retail department store gift card for patients who 
participate in the qualitative study. The gift card will be paid upon completion of the 
interview.
24.Compensation for Research-Related Injury

20
[Type text]
Because naloxone is an antidote of opioids and only minor adverse reactions were 
reported in the similar clinical studies, the investigators will not anticipate serious 
adverse reactions. The research team will encourage all study subjects to report any 
adverse reactions from naloxone at each visit, if a subject uses the rescue kit. The 
research team will examine the causality and severity of the adverse reaction with the 
Naranjo algorithm and Common Terminology Criteria for Adverse Events (CTCAE) 
v4.0. If a serious adverse reaction occurs and the reaction is related to naloxone, the study 
team will compensate the patient for the cost of an emergency room visit and necessary 
patient’s care (primary care physician’s visit, medications, etc.).
25.Consent Process
The research team will obtain consent from all study subjects. The consent 
process will take place at the ASAP. The research team will provide enough time for a 
potential study candidate to understand the clinical study and to ask any study-related 
questions of the research team and study coordinator until all concerns are resolved. The 
research team also will explain that participation in the study will not affect the quality of 
a subject’s primary care, whether or not the subject agrees with the participation. As 
described in Section 24 in this protocol, healthcare providers at the ASAP will identify 
potential study candidates. The candidates will be asked if they are interested in taking 
part in the study. Then the candidate will be referred to an investigator on the team. The 
investigator will explain the clinical study and answer questions, such as about risks and 
benefits, from the study candidates. After the candidate understands the study and agrees 
to sign the informed consent form (ICF), the candidate becomes a study subject and will 
receive naloxone rescue kits. The research team will follow “SOP: Informed Consent 
Process for Research (HRP-090).” 
Non-English Speaking Subjects
We will not recruit patients who are not able to speak and understand English. 
According to the latest census data, 47% of the population of New Mexico is Hispanic or 
Latino (2012).10 Although the statistics shows that the major ethnicity in NM is Hispanic 
or Latino, the majority of the patient population at ASAP is English speaking, with only 
2% of the patients are Spanish speakers. Currently there is a lack of personnel and 
resources available to translate all relevant materials into Spanish, should the patient 
population change then an effort will be made to include Spanish consent and a 
translator.
Subjects who are not yet adults (infants, children, teenagers)
The research team will not recruit infants, children, and teenagers 17 or younger 
in this study. 
Cognitively Impaired Adults
The research team will not recruit cognitively impaired adults in this study. 
Adults Unable to Consent
The research team will not recruit adults unable to consent in this study.

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26.Documentation of Consent
The research team will follow “SOP: Written Documentation of Consent (HRP-
091).” 
27.Study Test Results/Incidental Findings
We will not share the study test results with study participants during the study period. 
However, the research team will publish the data to addiction psychiatry-related or pain 
management-related journal. Once the article become available in public, then we will 
share the article with the participants.
  
28.Sharing Study Progress or Results with Subjects
The results will not be shared with the study subjects. The investigator will not share any 
identified patient health related information with the study sponsor. 
29.Inclusion of Vulnerable Populations

The research team will not recruit infants, children, and teenagers 17 or younger 
in this study.

The research team will recruit pregnant and breast feeding women. Benefits from 
naloxone auto-injector outweighs the risks of opioid overdose death rather than 
the risk of congenital malformation due to naloxone. Additionally, pregnancy risk 
category of the naloxone is B.21,22 See definition below. Data on the excretion of 
naloxone in breast milk is unknown. 
o
Pregnancy category B: 
Animal reproduction studies show no evidence of impaired fertility or 
harm to the fetus; however, no adequate and well-controlled studies 
have been conducted in pregnant women. 
30.Community-Based Participatory Research
Not applicable.
31.Research Involving American Indian/Native Populations
We do recruit Native Americans but this research is not intended to target American 
Indian/Native populations nor is it conducted on tribal lands. While participants may be 
of these populations we are not seeking out these participants. We have a wealth of 
experience with persons of tribal descent and therefore we are sensitive to the local 
population in terms of tribal regulations, applicable laws and standards of professional 
conduct and practice. 
32.Transnational Research
Not applicable
33.Drugs or Devices
Drug23 

Generic name: Naloxone hydrochloride injection, USP

Brand name: EVZIO 

22
[Type text]

Strength: 0.4 mg/0.4 mL in each kit21 and 2 mg/0.4 mL in each kit22

NDC number
o
0.4 mg kit: 60842-030-0121
o
2 mg kit: 60842-051-0122

Manufacturer: 
Kaleo
Richmond, VA 23219

Pharmacology24
o
Naloxone is an antidote of opioids and has been used frequently for 
patients whose condition is opioid intoxication or for patients with 
respiratory depression with therapeutic opioid doses. Several 
formulations are available: intravenous, intramuscular, and 
subcutaneous injections are commonly used administration routes. 
However, adverse events due to opioid overdose can occur at any time. 
Thus, a convenient drug formulation of naloxone is necessary to 
administer naloxone to prevent drug overdose deaths, regardless of a 
patient’s knowledge.

Pharmacokinetics
o
Time to peak: 15 minutes 
o
Maximum serum concentration 1.24 ng/mL
o
Time to maximum concentration: 20 minutes
o
Metabolism: 

Primarily metabolism route: liver via glucuronidation 
o
Elimination half-life: 1.36 hours
o
Excretion: Urine (as metabolites)

Indications24
o
Emergency treatment of known or suspected opioid overdose, 
as manifested by respiratory and/or central nervous system 
depression. 

Immediate administration as emergency therapy in 
settings where opioids may be present.

Necessity of Investigational New Drug (IND) application
o
No. This product has an FDA approval in 2014.

Drug storage
o
Naloxone auto-injector is stored at 15-25°C (59-77°F).21 Access to the 
naloxone auto-injector should be limited to the investigators at UNM 
ASAP. 
o
The naloxone auto-injectors are stored in a secure area in the 
medication room in UNM ASAP. A pharmacist at UNM 
Investigational Pharmacy will maintain logs to track who the naloxone 
autoinjectors are dispensed for regulatory requirements (Appendix 7 
and 8).17 

Drug destruction
o
At the end of the clinical trial, all unused naloxone kits will be 

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transferred to Dr. Takeda. She will contact the Safety Office at the 
University of New Mexico, and will follow the direction for drug 
destruction accordingly. She will also create a detail report to explain 
following items upon destruction:

Numbers of kit remaining at the end of the study

Expiration date and lot number of naloxone 

Reason for the destruction
Dr. Takeda will keep the document at least 5 years from the end of the study.

24
[Type text]
Checklist Section
This section contains checklists to provide information on a variety of topics that require special 
determinations by the IRB.  Please complete all checklists relevant to your research.
I.
Waivers or Alterations of Consent, Assent, and HIPAA Authorization
A. Partial Waiver of Consent for Screening/Recruitment
1. Describe the data source that you need to review (e.g., medical records):
Medical record (PowerChart)
2. Describe the purpose for the review (e.g., screening):
Screening
3. Describe who will conducting the reviews (e.g., investigators, research staff):
Investigators and research coordinator
4. Do all persons who will be conducting the reviews already have permitted 
access to the data source?
 Yes
 No. Explain:      
5. Verify that each of the following are true or provide an alternate justification 
for the underlined regulatory criteria:
a) The activity involves no more than minimal risk to the subjects 
because the records review itself is non-invasive and the results of the 
records review will not be used for any purposes other than those 
described above.
 True
 Other justification:      
b) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects because eligible subjects will be approached for 
consent to participate in the research and are free to decline.  Further, 
the information accessed during the records review will not be 
disclosed to anyone without a legitimate purpose (e.g., verification of 
eligibility).
 True
 Other justification:      
c) The research could not practicably be carried out without the waiver or 
alteration because there is no other reasonably efficient and effective 
way to identify who to approach for possible participation in the 
research.  
 True
 Other justification:      
d) Whenever appropriate, potentially eligible subjects will be presented 
with information about the research and asked to consider 
participation.  (Regulatory criteria: Whenever appropriate, the 

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subjects will be provided with additional pertinent information after 
participation.)
 True
 Other justification:      
Partial Waiver of HIPAA Authorization for Screening/Recruitment
1. Will you be recording any PHI when conducting the records review to identify 
potential subjects and/or determine eligibility?
 Yes. Describe: 
A review of the medical records of current patients at the UNM ASAP is 
required to identify potential study subjects. This requires the use of the 
medical record number to review the medical record for eligibility 
requirements.
 No
If you answered “Yes” to question 6 above, please describe when you will destroy 
identifiers (must be the earliest opportunity consistent with the conduct of the 
research) or provide justification for why they must be retained:
The data will be kept until all data analysis is completed, the use of PHI for 
screening involves no more than minimal risk as we already have access to 
this information for clinical care of these patients. PHI that may be 
used/viewed for screening will not be retained in any way after the consent 
process has been completed. If the patient is determined to not be an eligible 
participant or declines consent all PHI that may have been collected during 
screening will be destroyed immediately and will not be retained in any way. 
If the patient is determined to be eligible the patient will be consented and will 
sign a HIPAA authorization at that time. Any PHI collected for screening 
purposes will be destroyed at the earliest time possible and will not be 
disclosed or re-used.
2.
The PHI accessed or recorded for identification/screening purposes will 
not be reused or disclosed to (shared with) any other person or entity, except as 
required by law, for authorized oversight of the research study, or for other 
research for which the use or disclosure of the PHI would be permitted under the 
Privacy Rule.
 True
 False
B. Waiver of Documentation of Consent – not applicable for our study
1. Are you requesting a waiver of documentation of consent for some or all 
subjects?
 All
 Some. Explain:      

26
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2. Provide justification for one of the following:
a) That the only record linking the subject and the research would be the 
consent document and the principal risk would be potential harm 
resulting from a breach of confidentiality. Each subject will be asked 
whether the subject wants documentation linking the subject with the 
research, and the subject's wishes will govern.
     
b) That the research presents no more than minimal risk of harm to 
subjects and involves no procedures for which written consent is 
normally required outside of the research context.
     
3. Do you intend to provide subjects with a written statement regarding the 
research in lieu of a traditional consent form?
 Yes. Please attach a copy to your submission in Click.
 No
C. Alteration of Consent – not applicable for our study
Note: FDA-regulated research is not eligible for an alteration of consent.
1. Which element(s) of consent do you wish to eliminate and why?
     
2. Which element(s) of consent do you wish to alter and why?
     
3. Provide justification for each of the following regulatory criteria:
a) The research involves no more than minimal risk to the subjects:
     
b) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects:
     
c) The research could not practicably be carried out without the waiver or 
alteration:
     
d) Whenever appropriate, the subjects will be provided with additional 
pertinent information after participation:
     
D. Full Waiver of Consent/Parental Permission – not applicable for our study
Note: FDA-regulated research is not eligible for a full waiver of consent using these 
criteria.  If you believe that your FDA-regulated research may be eligible for a waiver 
under another mechanism, such as planned emergency research, contact the HRPO 
for assistance in determining what information to provide to the HRRC.
1. Are you requesting a waiver for some or all subjects?
 All
 Some. Explain:      
2. Provide justification for each of the following regulatory criteria:
a) The research involves no more than minimal risk to the subjects:
     

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b) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects:
     
c) The research could not practicably be carried out without the waiver or 
alteration:
     
d) Whenever appropriate, the subjects will be provided with additional 
pertinent information after participation:
     
E. Full Waiver of Consent/Parental Permission (Public Benefit or Service 
Programs) – not applicable for our study
1. Are you requesting a waiver for some or all subjects?
 All
 Some. Explain:      
2. Provide justification for each of the following regulatory criteria:
a) The research or demonstration project is to be conducted by or subject 
to the approval of state or local government officials and is designed to 
study, evaluate, or otherwise examine: (i) public benefit or service 
programs; (ii) procedures for obtaining benefits or services under those 
programs; (iii) possible changes in or alternatives to those programs or 
procedures; or (iv) possible changes in methods or levels of payment 
for benefits or services under those programs:
     
b) The research could not practicably be carried out without the waiver or 
alteration.
     
F. Full Waiver of HIPAA Authorization – not applicable for our study
1. Are you requesting a waiver of authorization for some or all subjects?
 All
 Some. Explain:      
2. Describe your plan to protect health information identifiers from improper use 
and disclosure:
     
3. Describe your plan to destroy identifiers at the earliest opportunity consistent 
with conduct of the research (absent a health or research justification for 
retaining them or a legal requirement to do so):
     
4. Describe why the research could not practicably be conducted without the 
waiver or alteration:
     
5. The PHI accessed or recorded for identification/screening purposes will not be 
reused or disclosed to (shared with) any other person or entity, except as 
required by law, for authorized oversight of the research study, or for other 
research for which the use or disclosure of the PHI would be permitted under 

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the Privacy Rule.
 True
 False
G. Other Waiver Types – not applicable for our study
II. Vulnerable Populations
A. Adults with Cognitive Impairments – not applicable for our study
1. Describe why the objectives of the study cannot be met without inclusion of 
adults with cognitive impairments.
2. Describe how capacity to consent will be evaluated.
     
3. If subjects may regain capacity to consent, or if subjects may have fluctuating 
capacity to consent, describe your plans to evaluate capacity to consent 
throughout the research and to obtain consent to continue participation if 
capacity is regained.
     
4. Describe your plans, if any, to provide information about the research to 
subjects and the steps you will take to assess understanding.
     
5. Describe your plans to obtain assent, including whether assent will be 
obtained from none, some, or all subjects.
     
6. Describe why risks to subjects are reasonable in relation to anticipated 
benefits to the subjects.
     
7. If this study involves a health or behavioral intervention, describe why the 
relation of the anticipated benefit to the risk of the research is at least as 
favorable to the subjects as that presented by alternative procedures.
     
8. Describe your plans for monitoring the well-being of subjects including any 
plans to withdraw subjects from the research if they appear to be unduly 
distressed.
     
B. Children – not applicable for our study
Complete this checklist if the subject population will include children.
1. Select the category of research that you believe this research falls within and 
provide justification for any associated criteria.  If there are different 
assessments for different groups of children or arms (e.g., placebo vs. drug), 
include a memo to provide an assessment for each group.  
 Research not involving greater than minimal risk. (Minimal risk means 
that the probability and magnitude of harm or discomfort anticipated 
in the research are not greater in and of themselves than those 
ordinarily encountered in daily life or during the performance of 
routine physical or psychological examinations or tests.)
 Research involving greater than minimal risk but presenting the 

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prospect of direct benefit to the individual subjects.
Provide justification for each of the following criteria:
(1) The risk is justified by the anticipated benefit to the subjects:
     
(2) The relation of the anticipated benefit to the risk is at least as 
favorable to the subjects as that presented by available 
alternative approaches:
     
 Research involving greater than minimal risk and no prospect of direct 
benefit to individual subjects, but likely to yield generalizable 
knowledge about the subject's disorder or condition.
Provide justification for each of the following criteria:
(1) The risk represents a minor increase over minimal risk:
     
(2) The intervention or procedure presents experiences to subjects 
that are reasonably commensurate with those inherent in their 
actual or expected medical, dental, psychological, social, or 
educational situations:
     
(3) The intervention or procedure is likely to yield generalizable 
knowledge about the subjects' disorder or condition which is of 
vital importance for the understanding or amelioration of the 
subjects' disorder or condition
     
C. Pregnant Women and Fetuses
Provide justification for each of the following:
1. Where scientifically appropriate, preclinical studies, including studies on 
pregnant animals, and clinical studies, including studies on non-pregnant 
women, have been conducted and provide data for assessing potential risks to 
pregnant women and fetuses.
The research team will recruit pregnant and breast feeding women. Benefits 
from naloxone auto-injector outweighs the risks of opioid overdose death 
rather than the risk of congenital malformation due to naloxone. Additionally, 
pregnancy risk category of the naloxone is B.21 See definition below. Data on 
the excretion of naloxone in breast milk is unknown. 
o
Pregnancy category B: 
Animal reproduction studies show no evidence of impaired fertility 
or harm to the fetus; however, no adequate and well-controlled 
studies have been conducted in pregnant women. 
2. The risk to the fetus is caused solely by interventions or procedures that hold 
out the prospect of direct benefit for the woman or the fetus; or, if there is no 
such prospect of benefit, the risk to the fetus is not greater than minimal and 
the purpose of the research is the development of important biomedical 
knowledge which cannot be obtained by any other means.
Naloxone hydrochloride was administered during organogenesis to mice. 

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These studies demonstrated no embryotoxic or teratogenic effects due to 
naloxone hydrochloride. But benefits from naloxone auto-injector outweighs 
the risks of opioid overdose death rather than the risk of congenital 
malformation due to naloxone.
3. Any risk is the least possible for achieving the objectives of the research.
Naloxone is only recommended for use during pregnancy when there are no 
alternatives and benefit outweighs risk. But, again, benefits from naloxone 
auto-injector outweighs the risks of opioid overdose death rather than the risk 
of congenital malformation due to naloxone.
D. Neonates of Uncertain Viability or Nonviable Neonates – not applicable for our 
study
Provide justification for each of the following:
1. Where scientifically appropriate, preclinical and clinical studies have been 
conducted and provide data for assessing potential risks to neonates.
     
2. Each individual providing consent is fully informed regarding the reasonably 
foreseeable impact of the research on the neonate.
     
3. Individuals engaged in the research will have no part in determining the 
viability of a neonate.
     
4. The research holds out the prospect of enhancing the probability of survival of 
the neonate to the point of viability, and any risk is the least possible for 
achieving that objective, or, the purpose of the research is the development of 
important biomedical knowledge which cannot be obtained by other means 
and there will be no added risk to the neonate resulting from the research
     
E. Nonviable Neonates – not applicable for our study
Complete this checklist if the subject population will include nonviable neonates.
Provide justification for each of the following:
1. Where scientifically appropriate, preclinical and clinical studies have been 
conducted and provide data for assessing potential risks to neonates.
     
2. Each individual providing consent is fully informed regarding the reasonably 
foreseeable impact of the research on the neonate.
     
3. Individuals engaged in the research will have no part in determining the 
viability of a neonate.
     
4. The purpose of the research is the development of important biomedical 
knowledge that cannot be obtained by other means.
     
Verify each of the following:

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5. Vital functions of the neonate will not be artificially maintained
 True
 False
6. The research will not terminate the heartbeat or respiration of the neonate
 True
 False
7. There will be no added risk to the neonate resulting from the research
 True
 False
F. Biomedical and Behavioral Research Involving Prisoners – not applicable for 
our study
1. Select and justify which allowable category of research involving prisoners 
this research falls within:
 Study of the possible causes, effects, and processes of incarceration, and of 
criminal behavior, provided that the study presents no more than minimal 
risk and no more than inconvenience to the subjects
     
 Study of prisons as institutional structures or of prisoners as incarcerated 
persons, provided that the study presents no more than minimal risk and 
no more than inconvenience to the subjects
     
 Research on conditions particularly affecting prisoners as a class (for 
example, vaccine trials and other research on hepatitis which is much 
more prevalent in prisons than elsewhere; and research on social and 
psychological problems such as alcoholism, drug addiction, and sexual 
assaults)
     
 Research on practices, both innovative and accepted, which have the intent 
and reasonable probability of improving the health or well-being of the 
subject
     
 Epidemiologic studies in which the sole purpose is to describe the 
prevalence or incidence of a disease by identifying all cases or to study 
potential risk factor associations for a disease, the research presents no 
more than Minimal Risk and no more than inconvenience to the subjects, 
and Prisoners are not a particular focus of the research.
     
2. Provide justification for each of the following regulatory criteria:
a) Any possible advantages accruing to the prisoner through his or her 
participation in the research, when compared to the general living 
conditions, medical care, quality of food, amenities and opportunity 
for earnings in the prison, are not of such a magnitude that his or her 
ability to weigh the risks of the research against the value of such 
advantages in the limited choice environment of the prison is impaired

32
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b) The risks involved in the research are commensurate with risks that 
would be accepted by nonprisoner volunteers
     
c) Procedures for the selection of subjects within the prison are fair to all 
prisoners and immune from arbitrary intervention by prison authorities 
or prisoners. Unless justification is provided, control subjects must be 
selected randomly from the group of available prisoners who meet the 
characteristics needed for that particular research project
     
d) The information is presented in language which is understandable to 
the subject population
     
e) Adequate assurance exists that parole boards will not take into account 
a prisoner's participation in the research in making decisions regarding 
parole, and each prisoner is clearly informed in advance that 
participation in the research will have no effect on his or her parole
     
f)
When appropriate, adequate provision has been made for follow up 
examination or care after research participation, taking into account 
the varying lengths of individual prisoners' sentences, and for 
informing participants of this fact
     
III.Medical Devices – not applicable for our study
A. Device Name:       
B. Manufacturer:       
C. Does the research involve a Significant Risk Device under an IDE?
 Yes. Include documentation of the FDA approval of the IDE with your submission.  
Acceptable methods of documentation include: (1) FDA letter noting IDE number 
and approval status; (2) Industry sponsor letter noting IDE number and FDA 
approval status; or (3) FDA-approved industry sponsor protocol with IDE number 
noted 
 No
D. Is the research IDE-exempt?
 Yes. Include a FDA letter with your submission noting the determination that the 
research is IDE-exempt or a letter from the sponsor (or sponsor-investigator) 
justifying why they believe the research is IDE-exempt*.  
 No
E. Does the research involve a Non-Significant Risk (NSR) Device?
 Yes. Include a FDA letter with your submission noting the determination that the 
research is NSR or a letter from the sponsor (or sponsor-investigator) justifying why 
they believe the research is NSR**.  
 No
* This FDA guidance includes a description for when a device study is exempt from the 

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IDE requirements: 
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf 
**This FDA guidance includes information on how to differentiate between Significant 
Risk and Non-Significant Risk device studies: 
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf 

34
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1.
United States Department of Health and Human Services, Substance Abuse and Mental 
Health Services Administration, Center for Behavioral Health Statistics and Quality. 
National Survey on Drug Use and Health, 2010. 2014; ICPSR32722-
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McGregor T, Parkar M, Rao S. Evaluation and management of common childhood 
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Substance Abuse and Mental Health Services Administration. Results from the 
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Rockville, MD: Substance Abuse and Mental Health Services Administration;2014.
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National Institute on Drug Abuse. Monitoring the Future Study: Trends in Prevalence of 
Various Drugs. Monitoring the Future 2015; http://www.drugabuse.gov/trends-
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Prevention CfDCa. Policy Impact: Prescription Painkiller Overdoses. Injury Prevention 
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Health NMDo. Overview of Opioid Risk. Opioid Safety 2011; 
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Prescription Drug Misuse and Overdose Prevention and Pain Management Advisory 
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Boyer EW. Management of opioid analgesic overdose. N Engl J Med. 2012;367(2):146-
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Zedler B, Saunders W, Andrew J, Vick C, Murrelle L. Validation of a Screening Risk 
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