Conditions: Opioid Abuse Opioid Dependence Opioid-Related Disorders Opioid Use
Keywords: oxycodone lorcaserin Belviq
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 32
Healthy volunteers: no

Brief summary:
The overall goal of this project is to develop initial human data on effects of novel compounds on safety (interactions with oxycodone) and efficacy (subjective response to oxycodone) in non-treatment seeking opioid use disorder subjects. The compound to be studied will be the 5-HT2CR agonist lorcaserin. There are no known or reported adverse interactions between lorcaserin and oxycodone or other opioids.

Detailed description:
Lorcaserin is a serotonin (5-HT) 2C receptor agonist (Trade Name Belviq) approved for treatment of obesity. The study teams's preclinical research collaborators and others have shown that lorcaserin and other 5-HT2CR agonists have been shown to reduce drugs of abuse self-administration and cue reactivity in rodents including cocaine and nicotine. Recently, this data has been expanded to opioids. Rats trained to self-administer oxycodone showed a significant reduction in self-administration and oxycodone cue induced lever presses after lorcaserin administration.

This is a single center, double-blind, placebo-controlled, randomized, 1b/2a study. 18 subjects are planned. The following treatment regimens will be used:

Lorcaserin will be administered at a dose of 10mg twice daily. Placebo or Comparator - identical placebo capsules administered at the same time as lorcaserin.

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: Lorcaserin intervention 2: Placebo
Intervention descriptions: intervention 1: Lorcaserin will be administered at a dose of 10 mg twice daily for 5 days intervention 2: Placebo will be administered twice daily for for 5 days

Protocol document:
Prot_SAP_001.pdf: 
 
 
Title: Drug Interaction and Subjective Effects of Compounds for Opioid Use Disorder 
 
NCT #: NCT03143855 
 
Document date: 02/12/2018 
 
Document Type: Protocol and SAP 
 
 
 


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TABLE OF CONTENTS 
 
BACKGROUND 
11 
Overview of Non-Clinical Studies 
10 
Overview of Clinical Studies 11 
STUDY RATIONALE 
12 
Risk / Benefit Assessment 
12 
STUDY OBJECTIVES 
16 
Primary Objective 
16 
Secondary Objectives 16 
STUDY DESIGN 
16 
Study Overview 
16 
Criteria for evaluation 16 
Primary Efficacy Endpoint 
16 
Secondary Efficacy Endpoints 
17 
SUBJECT SELECTION 
17 
Study Population 
17 
Inclusion Criteria 
17 
Exclusion Criteria 
17 
Concurrent Medications 
18 
Allowed 
18 
Prohibited 
18 
STUDY TREATMENTS 
18 
Method of Assigning Subjects to Treatment Groups 18 
Blinding 
18 
Test and Control Formulation  
19 
Supply of Study Medication at the Site 
20 
Study Medication Accountability 
20 
STUDY PROCEDURES AND GUIDELINES 
20 
Clinical Assessments 20 
Clinical Laboratory Measurements (include sections as appropriate) 
22 
Pharmacokinetic Measurements 
23 
EVALUATIONS BY VISIT 23 
Visit 1 (Day/Week/Month # include visit window)   23 
Visit 2 (Day/Week/Month # include visit window) 24 
Visit 3 (Day/Week/Month # include visit window) 25 
Visit 4 (Day/Week/Month # include visit window) 25 
Visit 5 (Day/Week/Month #) 26 
Visit 6 (Follow-up or Day/Week/Month # include visit window) 26  
ADVERSE Experience REPORTING AND DOCUMENTATION 28 
Adverse Events 
28 


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Serious Adverse Experiences (SAE) 28 
Medical Monitoring 29 
Safety Management Plan 
4 
DISCONTINUATION And Replacement of subjects 
29 
Withdrawal of Subjects 
29 
Replacement of Subjects 
31 
Protocol Violations 
30 
DATA SAFETY MONITORING (optional Section – Include when appropriate) 30 
STATISTICAL METHODS AND CONSIDERATIONS 
31 
Data Sets Analyzed 
32 
Demographic and Baseline Characteristics 32 
Analysis of Primary Endpoint  
32 
Analysis of Secondary Endpoints 
32 
Interim Analysis 
33 
Sample Size and Randomization 
33 
DATA COLLECTION, RETENTION AND MONITORING 
34 
Data Collection Instruments 34 
Data Management Procedures 
34 
Data Quality Control and Reporting 34 
Archival of Data 
34 
Availability and Retention of Investigational Records 
35 
Subject Confidentiality 
35 
ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS 35 
Protocol Amendments  35 
Institutional Review Boards and Independent Ethics Committees 
35 
Informed Consent Form 
36 
Publications 
36 
 
 
 


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List of Abbreviations 
 
AE 
adverse event 
ALT 
alanine aminotransferase 
ASI-lite 
Addiction Severity Index 
AST 
aspartate aminotransferase 
BUN 
blood urea nitrogen 
CFR 
 
Code of Federal Regulations 
 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CGI-I 
Clinical Global Impression Improvement 
CGI-S 
Clinical Global Impression Severity 
CNS 
Central Nervous System 
COWS 
Clinical Opiate Withdrawal Scale 
CPT 
Cold Pressor Test 
CRF 
Case Report Form 
CRP 
C-reactive protein 
CRSU 
Clinical Research Services Unit 
DMC 
Data Monitoring Committee 
DMT 
Delayed Memory Task 
DSMB 
Data Safety Monitoring Board 
ESR 
erythrocyte sedimentation rate 
FDA 
Food and Drug Administration 
 
 
FTND 
Fagerstrom Test for Nicotine Dependence 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IL-8 
Interleukin-8 
IMT 
Immediate Memory Task 
IRB 
Institutional Review Board 


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IV 
intravenous 
KMSK 
Kreek-McHugh-Schluger-Kellogg Scale 
LDH 
lactate dehydrogenase 
NART 
National Adult Reading Test 
OCS 
Opioid Craving Scale 
OPUD 
Opioid Use Disorder 
PI 
Principal Investigator 
PK 
pharmacokinetic 
POMS 
Profile of Mood Sates 
SAE 
serious adverse experience 
SCID 
The Structured Clinical Interview for DSM-IV 
SCID-II 
The Structured Clinical Interview for DSM-IV Personality 
Disorders Module 
SOWS 
Subjective Opiate Withdrawal Scale 
VAS 
Visual Analog Scale 
 
 
 


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PROTOCOL SYNOPSIS 
TITLE 
Phase I drug interaction and subjective effects of compounds for 
Opioid Use Disorder 
SPONSOR 
F. Gerard Moeller, M.D. 
FUNDING 
ORGANIZATION 
National Institute on Drug Abuse 
NUMBER OF SITES 
1 
RATIONALE 
The overall goal of this project is to develop initial human data on 
effects of novel compounds on safety (interactions with opioid drug, 
e.g., oxycodone) and efficacy (subjective response to oxycodone) in 
non-treatment seeking opioid use disorder subjects. The compound to 
be studied will be the 5-HT2CR agonist lorcaserin. Lorcaserin has 
been shown to reduce oxycodone self-administration and cue 
reactivity in rodents (described in detail in Background section 
below). 
STUDY DESIGN 
This is a randomized, double-blind, placebo-controlled phase 1b/2a 
study. 
PRIMARY OBJECTIVE 
1. Assess interaction between lorcaserin and oxycodone in healthy 
opioid using subjects. 2. Assess effect of lorcaserin on subjective 
response to oxycodone in healthy opioid using subjects. 3. Assess 
effect of lorcaserin on oxycodone PK in healthy opioid using subjects.  
SECONDARY 
OBJECTIVES 
Assess effect of lorcaserin on response inhibition in healthy opioid 
using subjects. 
NUMBER OF 
SUBJECTS 
18 
SUBJECT SELECTION 
CRITERIA 
Inclusion Criteria: 
In order to participate in this study, subjects must: 
1. Males and females between 18 and 70 years-of-age. 
2. Understand the study procedures and provide written informed 
consent. 
3. Meet current DSM-5 criteria for opioid use disorder, at least 
moderate severity, but are not seeking treatment. 
4. Have at least one positive urine drug screen for opioids during 
screening to document opioid use. 
5. Have no clinically significant abnormalities in the judgment of the 
study physician in hematology and chemistry laboratory tests 
including liver function tests. 
6. Have no contraindications for study participation as determined by 
medical history and physical examination. 
7. Be able to demonstrate an understanding of study procedures and 
follow instructions including behavioral laboratory testing.  


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8. No pregnant or nursing women will be permitted in the study, and 
women must either be unable to conceive (i.e., surgically sterilized, 
sterile, or postmenopausal) or be using a reliable form of 
contraception (e.g., abstinence, birth control pills, intrauterine device 
with spermicide, or condoms). Men will be advised to use condoms. 
All females must provide negative pregnancy urine tests before study 
entry, at each visit during the study, and at the end of study 
participation. 
 
Exclusion Criteria: 
In order to participate in the study, subjects must not: 
1. Meet current DSM-5 diagnosis of any psychoactive substance use 
disorder other than opioids, cocaine, marijuana, or nicotine. Diagnosis 
of mild to moderate use disorder for alcohol will not be considered 
exclusionary. 
2. Have a current DSM-5 axis I psychiatric disorder other than 
substance use disorder including but not limited to Bipolar Disorder, 
Major Depressive Disorder, ADHD, or Schizophrenia or a 
neurological disorder requiring ongoing treatment and/or making 
study participation unsafe. 
3. Have any previous medically adverse reaction to oxycodone or 
other opioids or lorcaserin or history of serotonin syndrome. 
4. Have any untreated clinically significant medical disorder including 
cardiovascular, pulmonary, CNS, hepatic, or renal disorder.  
5. Have a history of seizures (excluding childhood febrile seizures), or 
loss of consciousness from traumatic injury for more than 30 minutes. 
6. Have significant current suicidal or homicidal ideation or a history 
of suicide attempt within the past 6 months. 
7. Have conditions of probation or parole requiring reports of drug use 
to officers of the court. 
8. Have impending incarceration.  
9. Have a positive HIV test by self-report or history.  
10. Be pregnant or nursing or not using a reliable form of 
contraception if able to conceive. All females must provide negative 
pregnancy urine tests at screening, and daily after hospital admission. 
11. Have any other illness, or condition, which in the opinion of the PI 
would preclude safe and/or successful completion of the study. 
12. Have taken any investigational drug within 90 days prior to 
baseline. 
13. Have an allergy to lorcaserin or oxycodone. 
14. Have taken or are currently taking drugs that are know to inhibit 
cytochrome P450, CYP3A or CYP2D6. 
15. ECG with QTc > 440ms. 
 


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TEST PRODUCT, 
DOSE, AND ROUTE OF 
ADMINISTRATION 
Lorcaserin 10mg  
Product will be administered orally twice daily for 3 days.   
CONTROL PRODUCT, 
DOSE AND ROUTE OF 
ADMINISTRATION 
Placebo 
Subjects who are randomized to placebo will receive identical 
capsules to the test product at the same time administered orally.  
DURATION OF 
SUBJECT 
PARTICIPATION AND 
DURATION OF STUDY 
Subjects will be on study for up to 28 days (including intervening 
weekends) 
Screening:  up to 21 days 
Baseline:  1 day 
Treatment :  4 days 
Follow-up:  2 days  
The total duration of the study is expected to be 18 months.  
CONCOMMITANT 
MEDICATIONS 
Allowed: Non-CNS Active medications 
 
Prohibited: CNS active medications that in the opinion of the PI may 
affect conduction or interpretation of the study. 
Medications which could potentially interact with lorcaserin or 
oxycodone, notably drugs inhibiting CYP3A or CYP2D6 
Efficacy Evaluations 
Primary outcome measures:  
1. Safety: Heart rate (HR), blood pressure (BP), respiratory rate, and 
pulse oximetry, pupil diameter measures during a placebo dose will be 
compared to HR and BP after each oxycodone dose (10 mg and 20 mg 
doses).  Changes in HR and BP induced by oxycodone dose along 
with lorcaserin will be compared to those without lorcaserin, by 
oxycodone dose level (10 mg and 20 mg doses), using repeated 
measures analysis of variance (ANOVA). Adverse event data will be 
compiled for lorcaserin and placebo cohorts and presented as 
summary statistics.  
2. Oxycodone PK: Plasma concentration-time profiles of oxycodone 
and its metabolites (noroxycodone, oxymorphone and 
noroxymorphone) after immediate-release oxycodone doses during 
placebo administration (Day 0,1) will be analyzed to obtain 
pharmacokinetic parameter estimates of oxycodone (cmax, tmax, 
AUC, apparent t½, CL/F for parent oxycodone and metabolic (AUC-) 
ratios for metabolites ) by individual. These parameters will be 
compared within subjects on sessions with lorcaserin (Day 4,5,6). 
3. Subjective response to oxycodone: Subjective response measures 
((visual analog scale (VAS) and Cold Pressor Test (CPT)) after 
oxycodone administration on day zero will be compared to same 
measures after oxycodone administration on day 4 between lorcaserin 
and placebo treated subjects to determine the extent to which these 
measures are modified by the administration of lorcaserin using 
repeated measures ANOVA. 


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Secondary Outcome Measures: 
1. Attention, Memory, and Response inhibition: Correct 
detections and commission errors on the Immediate and 
Delayed Memory Task (IMT/DMT) will be compared between 
lorcaserin and placebo subjects to determine the extent to 
which this measure is modified by the administration of 
oxycodone and lorcaserin using repeated measures ANOVA. 
2. Craving as measured by the opioid craving scale and brief 
substance craving scale will be compared between lorcaserin 
and placebo subjects to determine the extent to which this 
measure is modified by the administration of oxycodone and 
lorcaserin using repeated measures ANOVA. 
Planned Interim Analyses  When approximately 50% of patients have completed the study, an 
interim analysis for safety will be conducted by the DSMB. Serious 
adverse events will be monitored by the committee on an ongoing 
basis throughout the study. 
STATISTICS 
Primary Analysis Plan 
Initial analyses will evaluate group differences on demographic and 
baseline variables, will use contingency tables with chi-square testing, 
ANOVA’s, and examination of correlations between baseline 
variables subjective responses and clinical results. General data 
analysis procedures: Urn randomization will be used for gender to 
reduce any potential between-group differences (lorcaserin vs. 
placebo) on baseline variables. Prior to data analysis procedures, 
groups will be examined for differences in other baseline 
characteristics that could potentially influence treatment outcome. 
Any variables that differ between groups and are related to outcome 
measures will be examined as potential covariates in subsequent data 
analyses.  
Primary outcome measures:  
1. Safety: Heart rate (HR), blood pressure (BP), pulse oximetry, pupil 
diameter, and respiratory rate measures during a placebo dose will be 
compared to HR and BP after each oxycodone dose (10 mg and 20 mg 
doses).  Changes in HR and BP induced by oxycodone dose along 
with lorcaserin will be compared to those without lorcaserin, by 
oxycodone dose level (10 mg and 20 mg doses), using repeated 
measures analysis of variance (ANOVA). Adverse event data will be 
compiled for lorcaserin and placebo cohorts and presented as 
summary statistics.  
2. Oxycodone PK: Plasma concentration-time profiles of oxycodone 
and its metabolites after oxycodone doses during placebo 
administration (Day 0,1) will be analyzed to obtain pharmacokinetic 
parameter estimates(cmax, tmax, AUC, apparent t½, CL/F and 
metabolic (AUC-) ratios) by individual.  These parameters will be 
compared within subjects on sessions with lorcaserin (Day 4,5,6). 
3. Subjective response to oxycodone: Subjective response measures 
(VAS, CPT) after oxycodone administration on day zero will be 


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compared to VAS and CPT measures after oxycodone administration 
on day 4 between lorcaserin and placebo treated subjects to determine 
the extent to which these measures are modified by the administration 
of lorcaserin using repeated measures ANOVA. 
Secondary Outcome Measures: 
1. Attention, Memory, and Response inhibition: Correct 
detections and commission errors on the Immediate and 
Delayed Memory Task (IMT/DMT) will be compared between 
lorcaserin and placebo subjects to determine the extent to 
which this measure is modified by the administration of 
oxycodone and lorcaserin using repeated measures ANOVA. 
2. Craving as measured by the opioid craving scale and brief 
substance craving scale will be compared between lorcaserin 
and placebo subjects to determine the extent to which this 
measure is modified by the administration of oxycodone and 
lorcaserin using repeated measures ANOVA. 
Rationale for Number of 
Subjects 
Power Calculation and Sample Size: 
Rationale for sample size: Sample size for effect of lorcaserin on 
oxycodone self-administration was based on previous research 
showing effects of oxycodone on pain and subjective responses in an 
experimental laboratory session (Jones et al., 2016). In an effort to 
increase the power of the study, a Bayesian approach will also be 
utilized that incorporates information from previous studies.  This 
approach will use a Bayesian hierarchical model with subject at the 
lowest level of the hierarchy and treatment group at the second level.  
This model is analogous to the repeated measures ANOVA except 
that prior information will be introduced.  Since many similar studies 
have been conducted with oxycodone users and the same outcome 
measures we will assign an informative prior distribution on the 
control group where the mean and standard deviation are educated 
guesses from the information provided in previous study of Jones et 
al., (2016).  For the treatment group we will assume a priori no change 
in the mean from the control group and the standard deviation are 
similar to those as the experimental group of the study by Hart et al. 
(Hart et al., 2008).  The model will be calculated using standard 
Markov Chain Monte Carlo (MCMC) packages such as WinBUGS, 
OpenBUGS, JAGS or MCMCpack in R.  Because MCMC sampling 
techniques are being employed the quality of the samples from the 
posterior distribution will be checked using trace plots, effective 
sample size, potential scale reduction factor and Hellinger distances 
(for more on Bayesian analyses and MCMC sampling see (Gelman et 
al., 2013).  As necessary techniques such as discarding burn-in 
samples, thinning and over-disperse starting points will be employed 
in order to obtain a set of samples from the posterior distribution that 
have an effective sample size of 10,000 on all parameters.  All 
inferences will be made from this set of samples from the posterior 
distribution. To calculate the power for the acute effects of the study 
three analyses are considered using the paired differences of subjects 


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at baseline and acute time points.   
A two-sample test on the means is performed using: Wilcoxon test 
(non-parametric), T-test (parametric) and a Bayesian (parametric) 
approach.  While from a Bayesian paradigm the notion of power does 
not exist in the traditional sense, one can create a decision rule and 
loss function in such a way that the associated risk is analogous to the 
notion of power.  To understand the power of each of the methods a 
Monte Carlo study was performed utilizing 1,000 separate datasets for 
likely effect sizes and sample sizes. 
The power was calculated as the proportion of datasets in which the 
test “rejected” the null hypothesis.  The table below gives the power 
for each test across percent change in effect size and control group 
sample sizes, here the treatment group sample size was n2 = 12. 
Based on the table below, an n of 6 was chosen as the sample size for 
the placebo group. 
 
BACKGROUND 
Lorcaserin is a serotonin (5-HT) 2C receptor agonist (Trade Name Belviq) approved for treatment of obesity.  
Overview of Non-Clinical Studies 
Our preclinical research collaborators and others have shown that lorcaserin and other 5-HT2CR agonists have 
been shown to reduce drugs of abuse self-administration and cue reactivity in rodents including cocaine 
(Cunningham et al., 2011; Manvich et al., 2012) and nicotine (Levin et al., 2011). Recently, this data has been 
expanded to opioids. As shown in the figures below, rats trained to self-administer oxycodone showed a 
significant reduction in self-administration and oxycodone cue induced lever presses after lorcaserin 


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administration (Cunningham et al., unpublished data) 
In addition, a study was carried out in mice on the effects of lorcaserin on the oxycodone alteration of pain 
measures. As shown in the figures below, acute lorcaserin potentiated the effects of oral oxycodone on one 
measure of pain, the tail flick assay. However, it attenuated the effect of oxycodone on the hot plate assay. The 
tail flick assay is considered to be a spinal pain pathway, whereas the hot plate assay is considered to be a 
measure of supraspinal (central) pain response (Le Bars et al., 2001). This preliminary data suggests that 
lorcaserin may alter the pain reducing effects of oxycodone, which may differ based on whether the pain 
response is peripheral or central.   
 
Overview of Clinical Studies 
BELVIQ (lorcaserin hydrochloride) tablets, for oral use. BELVIQ is a serotonin 2C receptor agonist indicated 
as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults 
with an initial body mass index (BMI) of: 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) in 
the presence of at least one weight-related comorbid condition, (e.g., hypertension, dyslipidemia, type 2 
diabetes). In a preliminary report of a smoking cessation study, Eisai Inc. and Arena Pharmaceuticals Inc. 
announced results from a Phase 2 trial investigating lorcaserin HCl for smoking cessation. The trial 
demonstrated statistically significant improvement over placebo in reducing the number of patients who smoke 
after 12 weeks of treatment. Based on Arena media report dated November 3, 2014, the 12-week, randomized, 
double-blind, placebo-controlled trial assessed the efficacy and safety of lorcaserin as a potential aid to smoking 
cessation. In the trial, 603 active smokers were randomized to receive lorcaserin 10 mg once daily, 10 mg twice 
daily or placebo in a 1:1:1 ratio. At baseline subjects were dependent on nicotine averaging 18 cigarettes per 
day. Patients received medication for two weeks prior to attempting to quit around Day 15 of the trial. Subjects 
also received smoking cessation counseling during the trial. Results showed that the carbon monoxide 
confirmed continuous abstinence rate (CAR), was achieved by 5.6%, 8.7%, and 15.3% of patients in the 
placebo, once daily and twice daily groups, respectively (p-value = 0.003 and odds ratio = 3.02 for twice daily 
vs. placebo; the result for once daily vs. placebo was not statistically significant).  
Safety and tolerability data showed that there was a statistically significant difference in weight between 
lorcaserin twice daily and placebo (-0.98 kg and -0.01 kg, respectively, p-value = 0.0004). The most common 
adverse events during the study were headache, nausea, constipation, dizziness and dry mouth, similar to 
previous trials of lorcaserin. For more detail refer to Belviq prescribing information.  
 
 
 


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STUDY RATIONALE 
The overall goal of this project is to develop initial human data on effects of novel compounds on safety 
(interactions with oxycodone) and efficacy (subjective response to oxycodone) in non-treatment seeking opioid 
use disorder subjects. The compound to be studied will be the 5-HT2CR agonist lorcaserin. There are no known 
or reported adverse interactions between lorcaserin and oxycodone or other opioids.  
Risk / Benefit Assessment 
Potential risks are listed below. The primary risks to participate in this study are those involved from potential 
unexpected serious adverse events due to receiving oxycodone or lorcaserin. The risks of the medications are 
provided below. 
Risks of Lorcaserin Administration 
Lorcaserin is FDA approved for the treatment of obesity. According to the FDA briefing document on 
lorcaserin based on the clinical trials in patients with obesity, “the most common adverse events with an 
incidence in the lorcaserin group that clearly exceeded placebo were headache (16.8 vs. 10.1%), dizziness (8.5 
vs. 3.8%), nausea (8.3 vs. 5.3%), fatigue (7.2 vs. 3.6%), and dry mouth (5.3 vs. 2.3%). These events were 
typically dose-related, mild or moderate in severity and transient. Furthermore, the excess over placebo 
occurred primarily within the first several days of treatment for headache and dizziness. Rates of 
discontinuation for adverse events were similar for lorcaserin 10 mg BID (8.6%), 10 mg QD (7.5%), and 
placebo (6.8%). Serious adverse events were as expected for the population, and similar in both character and 
frequency in the lorcaserin and placebo populations.” Because lorcaserin has the potential to impair cognitive 
function, patients should be cautioned about operating hazardous machinery, including automobiles, until they 
are reasonably certain that lorcaserin therapy does not affect them adversely. In preclinical studies abnormalities 
in thyroid function and liver tests have been seen in animals, but no changes in thyroid function or liver function 
have been noted in humans. In patients with diabetes, a drop in blood sugar has been seen. Weight loss may 
increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin 
secretagogues (e.g., sulfonylureas); hypoglycemia was observed in clinical trials with lorcaserin. Lorcaserin has 
not been studied in combination with insulin. In other populations, lorcaserin has been associated with a modest 
increase in blood pressure.  
Other Potential Risks of Lorcaserin but not seen in Clinical Trials 
Risk of serotonin syndrome: As lorcaserin is a serotonergic medication, it carries the risk of serotonin syndrome 
associated with all serotonergic compounds. This risk could be increased by combining lorcaserin with other 
serotonergic compounds. Our own research experience using another serotonergic drug, citalopram with 
cocaine dependent subjects (Moeller et al., 2007) and another ongoing clinical trial has not seen any episodes of 
serotonin syndrome. Risk of valvular heart disease: Valvular heart disease has been seen in compounds that are 
5-HT2B agonists (Hutcheson et al., 2011). Lorcaserin is a 5-HT2C agonist, with minimal affinity for the 5-
HT2B receptor (see table 1 below). In addition, occurrence of valvular heart disease was examined in clinical 
trials with lorcaserin. In 3451 subjects who took lorcaserin 10mg twice daily for 1 year, 2.4% of patients who 
received lorcaserin and 2.0% of patients who received placebo developed valvular regurgitation on 
echocardiography (Belviq prescribing information). 
 
Table 1. Lorcaserin 5-HT Receptor Affinity (Belviq Prescribing Information) 
 


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Risk of Priapism: Other medications that have 5-HT2C receptor affinities have been shown to produce 
priapism. Due to this risk subjects will be warned regarding the need for prompt treatment of prolonged 
erections lasting more than four hours. 
 
Abuse Potential: Lorcaserin is a Schedule IV medication due to studies in humans showing that 
supratherapeutic doses of lorcaserin produced a rating of “high”. In a published study (Shram et al., 2011) 
subjective measures of drug response were obtained in recreational polydrug users after 20mg, 40mg, and 60mg 
of lorcaserin and compared with zolpidem (15mg and 30mg) and ketamine (100mg). Results of that study 
showed that on the visual analog scale (VAS) rating of “drug liking”, overall, the mean scores for zolpidem and 
ketamine were in the “liking” range of greater than 50 on a 100 point scale, whereas, ratings for lorcaserin were 
in the “disliking” range (less than 50). The effects were primarily due to higher doses of lorcaserin. On other 
VAS ratings, lorcaserin 40mg and 60mg produced a significant increase in the “high” rating but also produced a 
significant increase in the “feeling sick” rating. In contrast, zolpidem and ketamine were liked by the subjects. 
The authors’ conclusions regarding this study were that “This study demonstrated that lorcaserin has a very low 
potential for abuse by recreational polydrug users with a history of using perception-altering and central 
nervous system depressant drugs. Supratherapeutic doses of lorcaserin were significantly disliked, as 
demonstrated by the bipolar Drug Liking VAS (primary measure), and was associated with prominent negative 
effects.” (Shram et al, 2011). Based on the safety and abuse potential data from human studies described above 
a dosage regimen of 10mg twice daily was chosen for this study. 
 
Risks of Oxycodone Administration 
Primary adverse reactions to oxycodone include constipation, sedation, respiratory depression and hypotension. 
We will limit these potential risks in several ways: (1) We will enroll only physically healthy opioid using 
subjects with no evidence of cardiovascular or respiratory disease based on history, physical examination, ECG, 
and laboratory tests – all prospective subjects will be seen a Cardiologist on staff prior to the initiation of the 
study. (2) We will administer doses shown to be safe in previous studies that were selected to produces 
scientifically valid results. (3) We will monitor subjects closely in an outpatient hospital setting throughout the 
duration of action of the drug, under the supervision of medical personnel trained in basic life support, with 
immediate availability of physicians trained in advanced cardiac life support and resuscitation if needed. We 
will also employ a bedside monitor for heart rate, ECG, pulse oximetry and respiratory rate. Blood pressure will 
be measured non-invasively every 10 minutes for 1 hour after oxycodone treatment.  We have an intervention 
plan in place to deal with any adverse events that may occur, as described in the following paragraph. In the 
event of an adverse event, the research team and the hospital is fully prepared to respond to any situation that 
may arise. The general and psychiatric emergency rooms are located minutes away.  There is a 24-hour medical 
emergency code team in the hospital. Physicians and their designated medical staff are fully trained to respond 
to all types of medical and psychiatric emergencies. A fully equipped resuscitation cart is located on the unit 
with I.V. naloxone. This study will be conducted at the CRS unit, a specialized inpatient and outpatient research 
unit at VCU Medical Center. This unit has previously conducted phase I studies, including other drug studies 
such as cocaine studies in humans (Baker et al., 2007). In the highly unlikely event of a suspected of medical 
emergency (i.e. respiratory depression, significant hypotension) the subject will be promptly evaluated by one 
of the research physicians and either transferred to Step Down Unit, ICU or Emergency Department or 
prescribed the appropriate treatment and monitoring level. Low risk subjects such as those with resolution of 
symptoms, normalization of vital signs, non-diagnostic ECG, and lack of potentially lethal arrhythmias may be 
monitored in the CRSU (see Immediate Evaluation of Adverse Event form).  
Effects on addiction: An additional concern is exposure to oxycodone increasing opioid use. In recruiting our 
subjects, the inclusion criteria include current opioid use disorder. The risk of oxycodone administration on 
craving in general will be minimized through: 1) To enroll in this study, opioid use disorder subjects must not 
be seeking treatment. 2) Subjects will remain in the controlled outpatient environment for 3 hours after the last 


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dose of oxycodone. 3) At the time of leaving the hospital, risks of ongoing opioid use and opportunities for 
treatment are discussed with all subjects. 
Risks of Lorcaserin Combined with Oxycodone 
Lorcaserin was approved by the FDA for the treatment of obesity in June of 2012. Since that time there have 
been no reported interactions between lorcaserin and oxycodone or other opioids. There is no known theoretical 
interaction between 5-HT2CR agonists and mu opioid receptor agonists, either directly or through altering the 
metabolism of either drug when administered together other than the theoretical possibility of a serotonin 
syndrome, although this has never been reported.  
In a recent NIDA funded preclinical study described above, lorcaserin was administered with oxycodone to rats. 
No increased sedation was noted in the rodents after lorcaserin administration compared to placebo.  
 
Potential Risks Not Due to Study Medication 
Potential risks to participating in this study not involving medication include: unauthorized disclosure of 
confidential information; discomfort or embarrassment related to urine collection or questionnaires dealing with 
personal habits, lifestyle, drug or alcohol use; possible unwanted encounters with friends or associates in the 
treatment setting. 
Phlebotomy: There is the potential risk of bruising at the site of the blood draw for the blood chemistries and 
complete blood count and the intravenous catheter site for PK blood draws. This risk will be minimized by 
having blood drawn by a trained phlebotomist or nurse. 
Adequacy of Protection Against Risks 
Informed Consent Procedures. The informed consent process involves a detailed verbal description of the study, 
the behavioral intervention, and the study medication provided by a study staff member.  Staff will emphasize 
that participation is voluntary. Next, the Project Director or study coordinator will conduct an item-by-item 
reading of the consent form while the participant reads along. The participant then meets with a physician 
investigator to ask questions about the risks of the medical procedures in the study. In this initial interview, 
participants will be informed of the following: 
They have an opportunity for research participation involving a program to evaluate effects of the study 
medication on effects produced by administration of oxycodone.   
Subjects in the studies will be randomly assigned to receive study medication or placebo. All assignments are 
based on chance on a 2:1 ration of lorcaserin vs. placebo. 
As with all medications, there are risks to treatment with the study medication. These are enumerated in the 
section above describing potential risks to the medication. 
All participants will be asked to complete questionnaires and answer questions related to drug and alcohol use, 
personal habits, lifestyle and feelings.  The initial information collection will take approximately 2 hours; 
shorter data collection sessions will occur at each visit after the initial screening. 
All participants will be asked to provide a urine specimen for drug screening at each clinic visit.  
Participants may drop out at any time without penalty or loss of benefits to which they are otherwise entitled. 
Participants will be informed of procedures for ensuring their confidentiality, including: the issuance of a 
“Certificate of Confidentiality” by the federal government; the use of numbers, codes and/or pseudonyms rather 
than participants’ names; and the placement of all data in locked files.  
Participants will be informed that, despite participant confidentiality protections, research staff, under current 
state law, are required to report certain communicable diseases, and any incidents of sexual or physical abuse of 
a child or elder.   
Participants will be given the contact numbers of both the Principal Investigator and IRB to answer questions 
about the study or one’s rights as a human subject. 


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A copy of the signed form is made and given to the subject, another copy is held in the Principal Investigator’s 
records, and the original signed consent is kept in a separate, locked file accessible to the Institutional Review 
Board (IRB) upon request. Individuals who decide that they are interested in treatment for opioid use disorder 
will be assisted in selecting treatment services and self-help meetings from the community resource listings.  
Assessment of Adverse Events. Participants will be asked daily how they are doing and if they are having any 
problems. Any spontaneously reported symptoms or complaints will be recorded and reported to the IRB and 
NIDA and the FDA if events are classified as serious.  
 
Data monitoring to ensure subject safety and confidentiality.  A potential risk in studies involving drug-
dependent volunteers is breach of confidentiality. This will be limited by maintaining data files on the medical 
histories of subjects to be kept in a locked file cabinet in the P.I.’s offices, accessible only to the study P.I. and a 
study nurse as needed. Electronic media (i.e., computer-stored data, and data stored on CDs) will be password 
protected via encrypted code key known only to the senior study personnel.  
Furthermore, all subject information is coded with a unique numerical identifier. Protections of privacy of 
subjects’ medical information will be described to the prospective subjects as part of the enrollment interview 
and the informed consent procedures.  
 
As part of the Data and Safety Monitoring Plan, a Data and Safety Monitoring Board (DSMB) will monitor 
study processes and findings; part of the role of the DSMB will be to intercede to recommend halting 
enrollment of subjects if results definitively indicate that the study medication or protocol is harmful or in any 
way would negatively impact those individuals.   
 
Potential Benefits of the Proposed Research to the Subjects and Others 
Subjects in the study will receive close psychiatric attention. The potential benefits to society include decreased 
oxycodone and other opioid use if the study medications prove beneficial, with a resultant decrease in opioid 
morbidity and mortality, as well as a reduction in the overall social costs for opioid dependence. Of note, more 
Virginians die from opioid overdose than from automobile accidents, highlighting the importance of developing 
new treatments for opioid use disorder. 
 
Risk-Benefit Ratio 
The primary risks to participation to this research are those that result from exposure to the study medications. 
These risks are seen as reasonable since there are in place numerous procedures, ongoing and periodic, designed 
to detect adverse experiences that occur both at the level of the individual and at the level of the medication 
condition. Once detected, there are adequate procedures in place to determine the most appropriate method for 
addressing adverse events that occur to the individual or to a group of individuals in a specific medication 
condition. There are few anticipated physical, psychological, social, or legal risks. However, some possible 
risks to participating in these studies include: unauthorized disclosure of confidential information; discomfort or 
embarrassment related to urine collection or questionnaires dealing with personal habits, lifestyle, drug or 
alcohol use; and possible unwanted encounters with friends or associates in the study setting. If participants 
were to find any aspects of their involvement in the study psychologically or otherwise uncomfortable, they will 
first meet with the study physician to discuss the situation and determine if modifications can be made to 
accommodate them. If there is no apparent resolution available, the decision will be made whether or not to 
discontinue the participant from the study.  
 
Importance of the Knowledge to be Gained 


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The risks to participants are reasonable in relation to the anticipated benefits because: 
Staff will be trained and supervised to identify participants who are of danger to themselves or others.  Those 
participants found to be seeking treatment will be referred for appropriate care. 
The identification of effective treatments for oxycodone dependence would be a great benefit to society. 
 
If any Psychiatric or non-Psychiatric medical illness (other than substance abuse) is discovered during the study, 
subjects will be referred for additional treatment in the community. 
 
STUDY OBJECTIVES 
Primary Objective 
The primary objectives are to provide safety and PK information on potential drug interactions between 
lorcaserin and oxycodone in subjects with opioid use disorder, to provide information on effects of lorcaserin on 
subjective response to oxycodone. 
Secondary Objectives 
The secondary objective is to examine effects of lorcaserin and oxycodone on behavioral laboratory measures 
of attention, memory, and impulsivity in oxycodone use disorder subjects. 
 
STUDY DESIGN 
Study Overview 
The overall goal of this project is to develop initial human data on effects of novel compounds on safety 
(interactions with oxycodone) and efficacy (subjective response to oxycodone) in non-treatment seeking opioid 
use disorder subjects. This is a Phase I human drug interaction study examining the safety of concurrent 
administration of oxycodone with novel compounds, and the effects of the novel compounds on subjective 
response to oxycodone in non-treatment seeking opioid use disorder subjects. These data will provide important 
information for go/no-go decisions on phase II clinical trials using medications as a tool to enhance abstinence. 
The initial compound to be studied will be the 5-HT2CR agonist lorcaserin, which has been shown to reduce 
oxycodone self-administration and cue reactivity in rodents. In addition there is human safety data in obese 
subjects for lorcaserin as it is currently FDA approved for obesity, but there is no human opioid interaction/PK 
data and no PD data to support potential dosages for phase II clinical trials.  
This is a single center, double-blind, placebo-controlled, randomized, 1b/2a study. 18 subjects are planned.   
Screening data will be reviewed to determine subject eligibility.  Subjects who meet all inclusion criteria and 
none of the exclusion criteria will be entered into the study.  
The following treatment regimens will be used: 
Lorcaserin will be administered at a dose of 10mg twice daily. 
Placebo or Comparator – identical placebo capsules administered at the same time as lorcaserin. 
Total duration of subject participation will be up to 28 days. Total duration of the study is expected to be 18 
months.  
Criteria for evaluation 
Primary Efficacy Endpoint 
1. Safety: Heart rate (HR), blood pressure (BP), pulse oximetry, pupil diameter, and respiratory rate measures 
prior to oxycodone dosing will be compared to these measures after each immediate release oxycodone dose (10 
mg and 20 mg doses).  Changes in these measures induced by oxycodone along with lorcaserin will be 
compared to those without lorcaserin, by oxycodone dose level (10 mg and 20 mg doses), using repeated 
measures analysis of variance (ANOVA). Changes in ECG readings taken prior to dosing as compared to those 


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taken during/following oxycodone dosing will be reported as summary statistics. Adverse event data will be 
compiled for lorcaserin and placebo cohorts and presented as summary statistics.  
2. Subjective response to oxycodone: Subjective response measures (VAS and CPT) obtained prior to dosing 
will be compared between lorcaserin and placebo subjects to those during oxycodone dosing by oxycodone 
dose level to determine the extent to which these measures are modified by the administration of lorcaserin 
using repeated measures ANOVA. 
4. Oxycodone PK: Plasma concentration-time profiles of oxycodone after oxycodone dosing during placebo 
administration (Day 0,1) will be analyzed to obtain pharmacokinetic parameter estimates for oxycodone and its 
circulating metabolites, norxycodone, oxymorphone and noroxymporphone (cmx, tmax, AUC, apparent t½, 
CL/F and metabolic (AUC-) ratios for each metabolite) by individual. These parameters will be compared 
within subjects during treatment with lorcaserin (Day 4, 5, 6). 
Secondary Efficacy Endpoints 
1. Attention, Memory, and Response inhibition: Correct detections and Commission errors on the 
IMT/DMT will be compared between lorcaserin and placebo subjects to determine the extent to which 
this measure is modified by the administration of lorcaserin using repeated measures ANOVA. 
2. Craving as measured by the opioid craving scale and brief substance craving scale will be compared 
between lorcaserin and placebo subjects to determine the extent to which this measure is modified by the 
administration of oxycodone and lorcaserin using repeated measures ANOVA. 
 
SUBJECT SELECTION 
Study Population 
Subjects with a diagnosis of opioid use disorder who meet the inclusion and exclusion criteria will be eligible 
for participation in this study.   
 
Inclusion Criteria 
1. Males and females between 18 and 70 years-of-age. 
2. Understand the study procedures and provide written informed consent. 
3. Meet current DSM-5 criteria for opioid use disorder, at least moderate severity,  not seeking treatment. 
4. Have at least one positive urine drug screen for opioids during screening to document opioid use. 
Have no clinically significant abnormalities in the judgment of the study physician in hematology and 
chemistry laboratory tests including liver function tests. 
5. Have no contraindications for study participation as determined by medical history and physical 
examination. 
6. Be able to demonstrate an understanding of study procedures and follow instructions including 
behavioral laboratory testing.  
7. No pregnant or nursing women will be permitted in the study, and women must either be unable to 
conceive (i.e., surgically sterilized, sterile, or postmenopausal) or be using a reliable form of 
contraception (e.g., abstinence, birth control pills, intrauterine device with spermicide, or condoms). 
Men will be advised to use condoms. All females must provide negative pregnancy urine tests before 
study entry, at each visit during the study, and at the end of study participation.  
Exclusion Criteria 
1. Meet current DSM-5 diagnosis of any psychoactive substance use disorder other than opioids, cocaine, 
marijuana, or nicotine. Diagnosis of mild to moderate use disorder for alcohol will not be considered 
exclusionary. 
2. Have a current DSM-5 axis I psychiatric disorder other than substance use disorder including but not 
limited to Bipolar Disorder, Major Depressive Disorder, ADHD, or Schizophrenia or a neurological 
disorder requiring ongoing treatment and/or making study participation unsafe. 


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3. Have any previous medically adverse reaction to oxycodone or lorcaserin or history of serotonin 
syndrome. 
4. Have any untreated clinically significant medical disorder including cardiovascular, pulmonary, CNS, 
hepatic, or renal disorder.  
5. Have a history of seizures (excluding childhood febrile seizures), or loss of consciousness from 
traumatic injury for more than 30 minutes. 
6. Have significant current suicidal or homicidal ideation or a history of suicide attempt within the past 6 
months. 
7. Have conditions of probation or parole requiring reports of drug use to officers of the court. 
8. Have impending incarceration.  
9. Have a positive HIV test by self-report or history.  
10. Be pregnant or nursing or not using a reliable form of contraception if able to conceive. All females 
must provide negative pregnancy urine tests at screening, and daily after hospital admission. 
11. Have any other illness, or condition, which in the opinion of the PI would preclude safe and/or 
successful completion of the study. 
12. Have taken any investigational drug within 90 days prior to baseline. 
13. Have an allergy to lorcaserin or oxycodone. 
14. Have taken or currently taking prescription or over-the counter drugs know to inhibit CYP3A or 
CYP2D6. 
15. ECG with QTc > 440ms. 
 
Concurrent Medications 
All subjects should be maintained on the same medications throughout the entire study period, as medically 
feasible, with no introduction of new chronic therapies. 
Allowed Medications and Treatments 
Non-CNS active medications which are not known to have a potential interaction with oxycodone or lorcaserin 
would be allowed in this study. 
Prohibited Medications and Treatments 
The following medications are prohibited during the study and administration will be considered a protocol 
violation. 
Any CNS active medications that in the opinion of the PI may affect conduction or interpretation of the study. 
Any medications with a known interaction with oxycodone or lorcaserin (see 14 above) 
 
STUDY TREATMENTS 
Method of Assigning Subjects to Treatment Groups 
Up to 18 eligible patients will be randomly assigned to lorcaserin or placebo treatment groups in a 1:2 ratio 
using a SAS-based computer-generated randomization scheme developed by the study data management 
provider.   
Blinding 
Due to the objectives of the study, the identity of test and control treatments will not be known to investigators, 
research staff, or patients.  The following study procedures will be in place to ensure double-blind 
administration of study treatments.  
Access to the randomization code will be strictly controlled.   
Packaging and labeling of lorcaserin and placebo will be identical to maintain the blind.  
Lorcaserin concentrations will not be analyzed till the end of the study. 


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The study blind will be broken on completion of the clinical study and after the study database has been locked.  
During the study, the blind may be broken only in emergencies when knowledge of the patient’s treatment 
group is necessary for further patient management. Unblinding will occur by the PI contacting the research 
pharmacy to break the blind in case of emergency. 
Formulation of Test Product 
Lorcaserin HCL 10mg tablets (Belviq, Arena Pharmaceuticals) will be used for this study. To ensure blinding, 
tablets will be placed in gelatin capsules by the research pharmacist prior to administration. 
Oxycodone HCL 10mg IR tablets (generic OxyIR) .To ensure blinding, tablets will be placed in gelatin capsules 
by the research pharmacist prior to administration.  
Formulation of Control Product 
Gelatin placebo capsules identical to capsules that enclose the study drug will be used for placebo. Dextrose 
powder will be used as a filling in the capsules. 
Packaging and Labeling 
Each pill bottle of study drug will be labeled with the required FDA warning statement, the protocol number, a 
treatment number, the name of the study physician, and directions for patient use and storage.   
Administration of Study Drug 
Dosage/Dosage Regimen 
 If subjects meet inclusion criteria, they will be admitted as hospital outpatients for a total of 2 study days to 
maintain complete monitoring for adverse events. In addition, the outpatient oxycodone administration 
procedures will reduce the likelihood of increased oxycodone craving after oxycodone administration. While in 
the hospital subjects will undergo procedures as described below. Subjects will not be allowed to smoke 
cigarettes, as smoking is not allowed in the hospital or anywhere on the VCU campus. Subjects will have the 
option to use a nicotine patch dosed based on the amount of daily cigarettes smoked. Subjects will not be 
allowed to leave the CRS Unit nor receive visitors. Subjects who are unable to comply with these restrictions 
will be dropped from the study. After a screening oxycodone dosing to determine safety, eligible subjects will 
be randomized to Group A –placebo only or Group B –lorcaserin (10mg BID). Six subjects will be assigned to 
Group A (placebo) and 12 subjects will be assigned to Group B (active lorcaserin).  
Study Drug Dosage: Lorcaserin will be 10mg twice daily.  
 
Study Objectives and Outcome Measures 
 Objectives 
 Primary Objectives: 
1. Assess interaction between lorcaserin and oxycodone in healthy opioid using subjects.  
2. Assess effect of lorcaserin on subjective response to oxycodone in healthy opioid using subjects.  
3. Assess effect of lorcaserin on oxycodone PK in healthy opioid using subjects.  
Secondary Objectives: 
1. Assess effect of lorcaserin on response inhibition in healthy opioid using subjects. 
2. Assess effect of lorcaserin on opioid craving in healthy opioid using subjects. 
Outcome Measures  
The primary outcome measures are adverse events, respiratory responses (pulse oximetry and respiratory rate), 
cardiovascular responses (Heart rate (HR), blood pressure (BP), ECG measurements, pupil diameter, subjective 
response to oxycodone (visual analog scale and cold pressor test), and oxycodone blood PK. 
 Secondary outcome measures: attention, memory and impulsivity as measured by the immediate memory task 
(IMT) and delayed memory task (DMT), and Responses to Opioid Craving Scale and Brief Substance Craving 
Scale. 


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Study Drug Administration 
1) Day 0: All subjects will be admitted to the CRSU for Oxycodone Dosing Session 1 (Baseline). All subjects 
will receive placebo on Day 0 in a single blind fashion. All subjects will undergo an ascending dose oxycodone 
administration (10 and 20mg OxyIR) to ensure safety of later oxycodone studies. Vital signs including heart 
rate, blood pressure, respiration rate and pupil diameter, pulse oximetry will be obtained after placebo 
administration. Day 0 will be single-blind placebo, whereas all remaining study days will be double-blind. All 
subjects will be discharged from the CRSU at the end of study day 0. 
2) Days 1-3: All subjects will come to the CARI clinic for drug dispensing/monitoring. On days 1-3, subject 
group A will receive one placebo pill twice daily, and group B will receive one lorcaserin 10 mg pill in the 
morning while in the clinic and one matching lorcaserin 10 mg pill will be dispensed to the participant to take in 
the evening, for a total dose of 20 mg daily.  
3) Day 4: All subjects will be re-admitted to the CRSU on Day 4 for Oxycodone Dosing Session 2. To assess 
the safety and subjective effects of oxycodone in the presence of lorcaserin, subjects will receive ascending 
doses of oxycodone (0, 10 mg, 20 mg), with each oxycodone administration separated by 45 minutes 
Monitoring will be continued for 3 hours after the last dose of oxycodone. 
 
Dispensing 
Study drug will be dispensed by the research pharmacist and administered by the research nurse on the CRS 
unit. 
Supply of Study Drug at the Site 
Study drug will be provided to the CRS research unit after an order from the study physician. 
Storage 
At the testing facility, all lorcaserin and placebo must be kept in a secure, locked storage place with access 
limited to authorized study personnel only. Lorcaserin bottles must be kept at room temperature (15°C–25°C) 
until ready for administration with controlled access.  
Study Drug Accountability 
An accurate and current accounting of the dispensing and return of study drug for each subject will be 
maintained on an ongoing basis by a member of the study site staff.  The number of study drug dispensed and 
returned by the subject will be recorded on the Investigational Drug Accountability Record. The study staff 
must record an accurate accounting of each lorcaserin, and Oxycodone/placebo dispensation and assignment 
number, as well as the date dispensed. 
 
STUDY PROCEDURES AND GUIDELINES 
A Schedule of Events representing the required testing procedures to be performed for the duration of the study 
is diagrammed in Appendix 1.  
 
Prior to conducting any study-related activities, written informed consent and the Health Insurance Portability 
and Accountability Act (HIPAA) authorization must be signed and dated by the subject.  If appropriate, assent 
must also be obtained prior to conducting any study-related activities. 
 
Clinical Assessments 
Concomitant Medications 
All concomitant medication and concurrent therapies will be documented during screening at Outpatient 
Hospital study days, CARI clinic study days, and Follow-Up days.  Dose, route, unit frequency of 
administration, and indication for administration and dates of medication will be captured. 


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Clinical Opiate Withdrawal Scale (COWS) and Subjective Opiate Withdrawal Scale (SOWS) 
These scales will be administered each study day during screening, admission to the CRSU, and CARI clinic 
study days to determine the presence of symptoms indicative of opiate withdrawal. A score  > 5 on the scale 
would prohibit study participation. In the event of a positive urine drug screen for opiates the study physician 
will review the COWS/SOWS and the subject’s drug use history to determine the likelihood of opiate 
withdrawal which would also prohibit study participation. 
Demographics  
Demographic information (date of birth, gender, race) will be recorded at screening. 
Medical History  
Relevant medical history, including history of current disease, other pertinent respiratory history, and 
information regarding underlying diseases will be recorded at screening. 
Physical Examination 
A complete physical examination will be performed by qualified staff (MD, DO, NP).  New abnormal physical 
exam findings must be documented and will be followed by a physician or other qualified staff at the next 
scheduled visit. 
Vital Signs 
Body temperature, blood pressure, pulse and respirations will be performed after resting for 5 minutes at each 
study day. 
The Structured Clinical Interview for DSM-IV (SCID) 
The SCID (First et al, 2002) will be used to collect diagnostic information used to make eligibility 
determinations. This interview will be conducted by staff who will be trained by experienced SCID interviewers 
using standardized training videotapes from Biometrics Research, NY. This interview will be conducted at 
screening. 
Structured Clinical Interview for DSM-IV Personality Disorders Module (SCID-II) 
This instrument provides a DSM-IV axis II diagnosis, and will be used to determine a diagnosis of Antisocial 
Personality Disorder and Borderline Personality Disorder (First et al, 1997). This interview will be conducted at 
screening by trained staff. 
Kreek-McHugh-Schluger-Kellogg Scale (KMSK) 
This scale (Kellogg et al, 2003) will be used to quantify use of opioids, cocaine, marijuana, alcohol, and other 
substances of abuse by assessing the frequency, amount, and duration of use of the particular substance during 
the individual’s period of greatest consumption. The scale also assesses the mode of use, whether the substance 
use is current or past, and whether each substance is the substance of choice. This will be conducted at 
screening by trained staff. 
Addiction Severity Index (ASI-lite) 
This scale (Cacciola et al, 2007) will be used in conjunction with the KMSK as measures of baseline severity of 
substance use. This will be conducted at screening by trained staff. 
Fagerström Test for Nicotine Dependence (FTND) 
This is a short self-report questionnaire (Heatherton et al, 1991) designed to measure the construct of nicotine 
dependence, will be included to explore the potential moderating effects of tobacco dependence in relation to 
opioid use and response to treatment. This will be conducted at screening by trained staff. 
National Adult Reading Test (NART) 
The NART-R is a 61-item vocabulary test (Nelson and O’Connell, 1978) will be used to estimate general 
intellectual ability and to control for individual differences in subject’s premorbid level of intelligence. This test 
has been shown to have high inter-rater (.96-.98) and test-retest reliability (.98) and predictive validity (.74) 
with the WAIS-R IQ.  This will be conducted at screening. 


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Clinical Opiate Withdrawal Scale (COWS) 
The COWS is an 11-item scale (Wesson and Ling, 2003) designed to be administered by a clinician. This tool 
can be use in both outpatient and outpatients settings to reproducibly rate common signs and symptoms of 
opiate withdrawal and monitor symptoms over time. The summed score for the complete scale can be used to 
help clinicians determined the stage or severity of opiate withdrawal and assess the level of physical 
dependence on opioids.  
Subjective Opiate Withdrawal Scale (SOWS) 
The SOWS contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely).  
Immediate Memory Task (IMT) 
The Immediate Memory Task (IMT) is a behavioral task designed to measure a subject's ability to retain and 
subsequently identify a stimulus kept in memory. As well as the ability to inhibit impulsive responding. The 
task is computer driven and takes approximately 20 minutes to complete. A series of 5-digit numbers are 
displayed on the monitor for a 0.5 s blackout period. 
Delayed Memory Task (DMT) 
The Delayed Memory Task (DMT) similar to the IMT involves responding to matching numbers, but the 
numbers to be compared are separated by a filler sequence (e.g. 12345). 
Adjusting Delay Discounting Task 
Adjusting Delay Discounting Task- This task is designed to measure participants’ discounting rate when they 
are presented with the possibility of receiving a real reward.  
Opioid Craving Scale (OCS) 
The Opioid Craving Scale, a modification of the Cocaine Craving Scale, is a brief, 3-item measure used to 
measure opioid craving. The scale consists of 3 items rated on a visual analogue scale from 0-10. 
Cold Pressor Test (CPT) 
The analgesic effects of oxycodone will be evaluated with experimentally induced pain using the cold pressor test 
(CPT), a commonly used and well-established model for producing pain. Methods for the cold pressor test 
will be the same as previously published (Jones et al., 2016). Crushed ice is added to a cold tank, and warm 
water was placed in a warm tank. The temperature in the cold talk will be maintained at 4 °C in and the 
temperature in the warm tank will be maintained at 37°C. Each participant is asked to immerse a hand in the 
warm tank for 2 min (to equalize baseline skin temperature across participants), afterwards participants are 
asked to immerse the same hand in the cold tank for up to 2 minutes. During the cold water immersion 
subjective measures of pain are collected using a visual analog scale. Objective measures of pain during the 
cold water immersion include pain threshold (time in seconds to the first report of pain) and pain tolerance (time 
until removal of the hand from water). Immediately following the CPT, subjective ratings of pain will be 
measured using a shortened version of the McGill Pain Questionnaire and a visual analog scale.  
 
Adverse Events 
Information regarding occurrence of adverse events will be captured throughout the study. Duration (start and 
stop dates and times), severity, outcome, treatment and relation to study drug will be recorded on the case report 
form (CRF). 
 
Clinical Laboratory Measurements  
Hematology 


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Blood will be obtained and sent to each site’s clinical hematology lab a complete blood count (hemoglobin, 
hematocrit, red blood cell count, white blood cell count, white blood cell differential, and platelet count). 
Blood Chemistry Profile 
Blood will be obtained and sent to each site’s clinical chemistry lab for determination of serum sodium, 
potassium, chloride, bicarbonate, random glucose, BUN, creatinine, aspartate aminotransferase (AST/SGOT), 
alanine aminotransferase (ALT/SGPT), alkaline phosphatase, total bilirubin, direct bilirubin, albumin and LDH. 
Pregnancy Test 
A urine pregnancy test will be obtained from female subjects who are of childbearing age prior to their 
participation in the study. 
Urinalysis 
Urine will be obtained and sent to each site’s clinical laboratory for determination of color, specific gravity, pH, 
protein, glucose, ketones, and blood. 
Urine Drug Screen 
Urine will be obtained from all subjects to be tested for cocaine (benzoylecgonine), opiates and opioids, 
benzodiazepines, amphetamine, methamphetamine, and THC. 
Breathalyzer 
Breath alcohol level will be obtained from all subjects. Subjects who have a positive breath alcohol will be told 
that they must return at a later date with a negative breath alcohol in order to take part in study procedures. 
 
Pharmacokinetic Measurements 
Pharmacokinetic samples for analysis of oxycodone and its metabolites: Blood samples for analysis of the 
pharmacokinetics of 10/20mg oxycodone will be collected during treatment with 0 mg Lorcaserin (on Study 
Day 0,1) and during treatment with lorcaserin at 10mg twice daily (Study Day 4,5,6). Plasma oxycodone levels 
at these time points for each of those days:  0, 45, 90, 135, 180, 195, 330, 600, and 1440 minutes (on the 
following day). After separation of plasma by routine methods, samples will be frozen at -70°C until ready for 
analysis.  Plasma concentrations of oxycodone and metabolites (noroxycodone, oxymorphone and 
noroxymorphone) will be assayed by liquid chromatography-tandem mass spectrometry.   
 
EVALUATIONS BY VISIT (see Table 2. below for overview of study time course) 
 
Screening Conducted at CARI clinic (Days -21 to -1, can be extended based on ability to schedule day 0)  
Review the study with the subject and obtain written informed consent. 
Assign the subject a unique screening number. 
Record demographics data. 
Record medical history.  
Record concomitant medications. 
Administer COWS 
Administer SOWS 
Perform a complete physical examination (once during screening). 
Perform a complete neurological exam (once during screening). 
Perform a 12-Lead ECG (once during screening). 
Collect urine for clinical laboratory tests (urine drug screen, pregnancy test, urinalysis). 
Perform and record vital signs. 


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Perform and record Breathalyzer. 
Collect blood for clinical laboratory tests (serum chemistry and hematology) (once during screening). 
Perform psychiatric interviews (SCID, SCID-II) (once during screening). 
Conduct clinical assessments (KMSK, FTND, NART, ASI-lite, POMS, C-SSRS) (once during screening). 
Record brief substance craving scale, timeline follow back oxycodone use, and drug use history. 
Verify inclusion and exclusion. 
Schedule subject for Day 0 visit as soon as possible. 
 
Outpatient Hospital Visit 1 (Day 0) 
Report to CRS unit. 
Collect urine for pregnancy test and urine drug screen. 
Perform and record Breathalyzer. 
Administer COWS.  
Administer SOWS 
Perform and record vital signs. 
Perform a 12-Lead ECG. 
Perform a brief physical exam. 
Begin continuous pulse oximetry and physiological monitoring, pupils, subjective effects, CPT 
Administer placebo in morning. 
Administer IMT/DMT. 
Administer oxycodone for Dosing session 1. 
Collect blood samples for oxycodone pK. 
Update concomitant medications. 
Record Visual Analog Scale (VAS). 
Record adverse events. 
Conduct clinical assessments (POMS, CGI-S, C-SSRS, OCS). 
Administer IMT/DMT. 
Administer Delay Discounting Task 
Perform a 12-Lead ECG. 
Perform sobriety test, leave CRS unit. 
 
Study Days Conducted at CARI clinic (Days 1-3) 
Collect urine for pregnancy test and urine drug screen. 
Blood draw for oxycodone and metabolite levels 24 hours post oxycodone dose (day 1 only) 
Perform and record Breathalyzer and vital signs. 
Record adverse events. 
Administer COWS. 
Administer SOWS 
Document drug use by self-report over last 24 hours. 
Update concomitant medications. 
Conduct clinical assessments (POMS, CGI-I, C-SSRS, OCS). 


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Dispense study drugs (AM dose taken in clinic, PM dose given to participant) 
 
Outpatient Hospital Visit 2 (Day 4) 
Report to CRS unit. 
Collect urine for pregnancy test and urine drug screen. 
Perform and record Breathalyzer. 
Administer COWS.  
Administer SOWS 
Perform and record vital signs. 
Perform a 12-Lead ECG. 
Perform a brief physical exam and continuous cardiovascular monitoring. 
Begin continuous physiological monitoring, pupils, subjective effects, CPT 
Administer study drug in morning. 
Administer IMT/DMT. 
Administer oxycodone for Dosing session 2. 
Collect blood samples for oxycodone/lorcaserin pK. 
Update concomitant medications. 
Record Visual Analog Scale (VAS). 
Record adverse events. 
Conduct clinical assessments (POMS, CGI-S, C-SSRS, OCS). 
Administer IMT/DMT. 
Administer Delay Discounting Task 
Perform a 12-Lead ECG. 
Perform Sobriety test 
Leave CRS unit. 
 
Follow-Up Conducted at CARI clinic (Days 5, 6) 
Collect urine for pregnancy test and urine drug screen. 
Blood draw for oxycodone and metabolite levels 24 hours post oxycodone dose (Day 5) 
Perform and record Breathalyzer and vital signs. 
Perform a 12-Lead ECG and brief physical exam (Day 6 only). 
Record OCS and timeline follow back opioid use. 
Administer COWS 
Administer SOWS 
Update concomitant medication. 
Conduct clinical assessments (POMS, CGI-I (only Day 6), and C-SSRS). 
Record adverse events. 
 
 
 
 


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Table 2.  Time Course of Study 
 
Screening 
(up to six 
visits  
Days -21 
to -1) 
Baseline 
(Day 0 
Week 1) 
Day 1 
Week 2 
 
Day 2 
Week 2 
Day 3 
Week 2 
Day 4 
Week 2 
Day 5 
Week 2 
Day 6 
Week 3 
Location 
CARI 
CRSU 
CARI 
CARI 
CARI 
CRSU 
CARI 
CARI 
Test Drug 
 
Placebo 
Lorcaserin 
10mg BID 
or Placebo 
Lorcaserin 
10mg BID 
or Placebo 
Lorcaserin 
10mg BID 
or Placebo 
Lorcaserin 
10mg in 
AM or 
Placebo 
 
 
Oxycodon
e Dose 
 
0, 10, 
20mg 
 
 
 
0, 10, 
20mg 
 
 
Behaviora
l Measures 
Self-
report 
Drug Use  
Subjective 
responses, 
Cold 
pressor 
tests, 
IMT/DMT 
Delay 
Discountin
g 
 
 
 
Subjective 
responses, 
Cold 
pressor 
tests, 
IMT/DMT 
Delay 
Discountin
g 
 
 
Other 
Once 
during 
screening 
ECG and 
Routine 
Blood 
work 
Blood 
samples 
for PK for 
oxycodone 
Blood 
sample for 
PK for 
oxycodon
e 
 
 
Blood 
samples 
for PK for 
oxycodone 
Blood 
samples 
for PK for 
oxycodon
e 
Follow-
up for 
side 
effects 
Follow-
up for 
side 
effects 
UDS 
Obtained 
Obtained  
Daily  
Daily  
Daily 
Daily 
Obtained 
Obtaine
d 
 
 
On each day of oxycodone administration, the following schedule will be used for procedures: 
Time 
Procedure 
-15 
Begin continuous physiological monitoring, pupils, subjective effects, CPT, ECG 
0 
Lorcaserin or placebo, IMT/DMT 
30 
Subjective effects, pupils 
45 
Subjective effects, pupils, blood, CPT 


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60 
OXY 0 mg, PO 
75 
Subjective effects, pupils 
90 
Subjective effects, pupils, blood, CPT 
105 
OXY 10 mg, PO: Subjective effects, pupils 
120 
Subjective effects, pupils 
135 
Subjective effects, pupils, blood, CPT 
150 
OXY 20 mg, PO (cumulative dose of 30 mg): Subjective effects, pupils 
165 
Subjective effects, pupils 
180 
Subjective effects, pupils, blood, CPT 
195 
Subjective effects, pupils, blood 
210 
IMT/DMT, Delay Discounting 
225 
Subjective effects, pupils, CPT 
270 
Subjective effects, pupils, CPT 
315 
Subjective effects, pupils, CPT 
330 
Subjective effects, pupils, blood, CPT, ECG 
600 
Subjective effects, pupils, blood, Sobriety test 
 
Criteria for withholding Oxycodone Administration 
Oxycodone administration will not be initiated if: 
• Heart rate less than 50/min or abnormal cardiac rhythm  
• Blood pressure less than 90/60mmHg 
• Pulse Oximetry of 92% or less 
• Respiratory Rate < 6/min  
• Behavioral manifestations of oxycodone toxicity (moderate sedation or greater, inability to 
cooperate with study procedures). 
 
Stopping Criteria for Subject Participation 
Subject participation will be terminated if any of the following events occur: 
The following values do not return to acceptable limits within appropriate time frames 
(approximately 30 minutes); 
• Heart rate less than 50/min or abnormal cardiac rhythm  
• Blood pressure less than 90/60mmHg 
• Pulse Oximetry of 92% or less 
• Respiratory Rate < 6/min  
• Behavioral manifestations of oxycodone toxicity (moderate sedation or greater, inability to 
cooperate with study procedures). 
• QTc increase of more than 30ms from baseline on repeat ECG 
• Symptoms of serotonin syndrome (fever, agitation, confusion, rapid heart rate and high blood pressure 


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ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION 
Adverse Events 
Adverse Events (AEs) will be identified through daily interviews with participants and noted at any visit. The 
data will be entered on the standard VCU IRB AE and SAE forms. Continuous logs of all SAEs and AEs will 
be maintained. SAEs will be reported to the VCU IRB, the NIDA PO, the DSMB and the US FDA (when 
appropriate) as described above. In addition to immediate reports where appropriate, there will be annual 
reports and descriptions in the results section of publications. 
Table 3.  AE Severity Grading 
Severity (Toxicity Grade) 
Description 
Mild (1) 
Transient or mild discomfort; no limitation in activity; no 
medical intervention or therapy required. The subject may be 
aware of the sign or symptom but tolerates it reasonably well. 
Moderate (2) 
Mild to moderate limitation in activity, no or minimal medical 
intervention/therapy required. 
Severe (3) 
Marked limitation in activity, medical intervention/therapy 
required, hospitalizations possible. 
Life-threatening (4) 
The subject is at risk of death due to the adverse experience as it 
occurred. This does not refer to an experience that hypothetically 
might have caused death if it were more severe. 
 
AE Relationship to Study Drug 
The relationship of an AE to the study drug will be assessed using the following the guidelines in Table 4. 
Table 4.  AE Relationship to Study Drug 
Relationship 
to Drug 
Comment 
Definitely 
Previously known toxicity of agent; or an event that follows a reasonable 
temporal sequence from administration of the drug; that follows a known or 
expected response pattern to the suspected drug; that is confirmed by stopping 
or reducing the dosage of the drug; and that is not explained by any other 
reasonable hypothesis. 
Probably 
An event that follows a reasonable temporal sequence from administration of 
the drug; that follows a known or expected response pattern to the suspected 
drug; that is confirmed by stopping or reducing the dosage of the drug; and 
that is unlikely to be explained by the known characteristics of the subject’s 
clinical state or by other interventions. 
Possibly 
An event that follows a reasonable temporal sequence from administration of 
the drug; that follows a known or expected response pattern to that suspected 
drug; but that could readily have been produced by a number of other factors. 
Unrelated 
An event that can be determined with certainty to have no relationship to the 
study drug. 
Serious Adverse Experiences (SAE) 
An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: 


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• death 
• a life-threatening adverse experience 
• outpatient hospitalization or prolongation of existing hospitalization 
• a persistent or significant disability/incapacity 
• a congenital anomaly/birth defect  
Other important medical events may also be considered an SAE when, based on appropriate medical judgment, 
they jeopardize the subject or require intervention to prevent one of the outcomes listed.  
 
Serious Adverse Experience Reporting 
All adverse events (AEs) occurring during the course of the study will be collected, documented, and reported 
to the PI. The occurrence of AEs will be assessed at baseline and each clinic visit during the treatment phase of 
the study.  
 
AE’s deemed to be serious (SAEs), as defined by the FDA, will be systematically evaluated at each clinic visit. 
Any SAE, whether or not related to study, will be reported to the VCU IRB, the NIDA Program Officer (Aidan 
Hampson, and the FDA (when appropriate) within 24-48 hours. A full written report to all institutions will 
follow as soon as possible but in no more than three days.  The written report will be in the format required by 
the local IRB and will contain information regarding the date of the SAE, description of the SAE, severity 
rating (Grade 1 to 4), assessment of cause, whether the SAE indicates an increased risk for current or future 
subjects, and whether changes to the informed consent form will be necessary.   
 
In cases of early termination from the study due to SAE, the participant will have appropriate follow-up medical 
monitoring. Monitoring will continue until the problem has resolved or stabilized with no further change 
expected, is clearly unrelated to study medication, or results in death.  Outcome of SAEs will be periodically 
reported to NIDA. A summary of the SAEs that occurred during the previous year will be included in the annual 
progress report to NIDA. 
 
Medical Monitoring 
Dr. F. Gerard Moeller should be contacted directly at these numbers to report medical concerns or questions 
regarding safety. 
Phone: (804) 828-4134 
Pager: (804) 828-4999, pager 3479 
   
DISCONTINUATION AND REPLACEMENT OF SUBJECTS 
Early Discontinuation of Study Drug (Lorcaserin) 
A subject may be discontinued from study treatment at any time if the subject, the investigator, or the Sponsor 
feels that it is not in the subject’s best interest to continue.  The following is a list of possible reasons for study 
treatment discontinuation:  
Subject withdrawal of consent (or assent) 
Subject is not compliant with study procedures 
Adverse event that in the opinion of the investigator would be in the best interest of the subject to discontinue 
study treatment 
Protocol violation requiring discontinuation of study treatment 
Lost to follow-up 


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Sponsor request for early termination of study 
Positive pregnancy test (females) 
Chest discomfort or shortness of breath consistent with ischemia or other cardiac abnormality 
Systolic BP > 180 mmHg 
Diastolic BP > 110 mmHg 
Heart rate > Maximum predicted heart rate (> 220 – age x 0.85) bpm. 
Symptoms of serotonin syndrome (fever, agitation, confusion, rapid heart rate, and high blood pressure 
If a subject is withdrawn from treatment due to an adverse event, the subject will be followed and treated by the 
Investigator until the abnormal parameter or symptom has resolved or stabilized.   
All subjects who discontinue study treatment should come in for an early discontinuation visit as soon as 
possible and then should be encouraged to complete all remaining scheduled visits and procedures. 
All subjects are free to withdraw from participation at any time, for any reason, specified or unspecified, and 
without prejudice. 
Reasonable attempts will be made by the investigator to provide a reason for subject withdrawals.  The reason 
for the subject’s withdrawal from the study will be specified in the subject’s source documents Refer to Section 
10 for early termination procedures. 
Withdrawal of Subjects from the Study 
A subject may be withdrawn from the study at any time if the subject, the investigator, or the Sponsor feels that 
it is not in the subject’s best interest to continue.   
All subjects are free to withdraw from participation at any time, for any reason, specified or unspecified, and 
without prejudice. 
Reasonable attempts will be made by the investigator to provide a reason for subject withdrawals.  The reason 
for the subject’s withdrawal from the study will be specified in the subject’s source documents.   
Replacement of Subjects 
Subjects who withdraw from the study treatment will be replaced.   
Subjects who withdraw from the study will be replaced.   
 
Protocol Violations 
A protocol violation occurs when the subject, investigator, fails to adhere to significant protocol requirements 
affecting the inclusion, exclusion, subject safety and primary endpoint criteria.  Protocol violations for this 
study include, but are not limited to, the following: 
Failure to meet inclusion/exclusion criteria 
Use of a prohibited concomitant medication 
Failure to follow study procedures as described in the study protocol. 
Failure to comply with Good Clinical Practice (GCP) guidelines will also result in a protocol violation. The 
investigator will determine if a protocol violation will result in withdrawal of a subject. 
When a protocol violation occurs, it will be discussed with the investigator and a Protocol Violation Form 
detailing the violation will be generated. A copy of the form will be filed in the site’s regulatory binder. 
 
DATA SAFETY MONITORING  
a. The Data Safety and Monitoring Board includes, Michael J. Lennon (M.D., Richmond VA Hospital), and 
Ananda Pandurangi (M.D., VCU school of Medicine), and John M. Hettema (M.D., Ph.D., VCU school of 
Medicine), Roshanak Markley, (M.D. Cardiology VCU school of Medicine), Brandon Willis (DO, Emergency 


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medicine and toxicology VCU school of medicine), Spencer Hays, (statistician, VCU department of statistics). 
Members are individuals who are completely independent of the investigators and who have no financial, 
scientific, or other conflict of interest with the trial.  Each member will provide written documentation attesting 
to absence of conflict of interest.  
 
b.  Frequency of meetings 
The first meeting will take place face-to-face to discuss the protocol, any modifications of the trial, and to 
establish guidelines to monitor the study. The DSMB Chairperson and the PI will prepare the agenda to address 
the review of manual of operating procedures, modification of the study design, initiation of the trial, reporting 
of adverse events, stopping rules, interim analysis plan, etc.  
 
Meetings of the DSMB will be held at time points corresponding with annual progress reports.  Open DSMB 
meetings will be attended by the PI, co-investigators, and research staff member (as appropriate).  A closed 
DSMB session will be held at study completion and attendance will be limited to DSMB members and the PI.  
Meetings may be convened as conference calls as well as in person, although the initial meeting and meetings to 
discuss interim analysis will be face-to-face. An emergency meeting of the DSMB (open, closed, or executive 
session) may be called at any time by the Chairperson should questions of patient safety arise.  
 
Issues discussed at DSMB sessions will include conduct and progress of the study, patient accrual, compliance 
with protocol, and problems encountered. As patient-specific data and treatment group data may be presented at 
DSMB sessions, the discussion will be regarded as completely confidential.   
 
c.  Conflict of interest 
All participating investigators and DSMB members will declare any conflicts of interest before the study is 
initiated, annually, and in the event of changing circumstances. Beyond this, the investigators are blind to the 
conditions and the PI does not make active decisions about assignment or subject care or participation. This 
separation of activities diminishes the risk of harm to either science or subjects due to conflicts of interest.  
 
d.  Protection of confidentiality 
All materials, discussions and proceedings of the DSMB are completely confidential. Members and other 
participants in DSMB meetings will be expected to maintain confidentiality.  
 
e.  Monitoring activities 
After initial review and approval of the project, the monitoring activities of the DSMB will be to evaluate the 
progress of the trial, including periodic assessments of data quality and timeliness, participant recruitment, 
accrual and retention, participant risk versus benefit, performance of the trial site, and other factors that can 
affect study outcome. 
 
f.  Communication plans to IRB, NIDA, and FDA 
The DSMB will make recommendations to the PI, who will then communicate the recommendations to the 
NIDA PO, and if necessary, to the FDA.  Recommendations of the DSMB will be sent to the IRB as well.   
 
 
STATISTICAL METHODS AND CONSIDERATIONS 


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Prior to the analysis of the final study data, a detailed Statistical Analysis Plan (SAP) will be written describing 
all analyses that will be performed.  The SAP will contain any modifications to the analysis plan described 
below.   
Data Sets Analyzed 
Initial analyses will evaluate group differences on demographic and baseline variables, will use contingency 
tables with chi-square testing, ANOVA’s, and examination of correlations between baseline variables subjective 
responses and clinical results. General data analysis procedures: Urn randomization will be used for gender to 
reduce any potential between-group differences (lorcaserin vs. placebo) on baseline variables. Prior to data 
analysis procedures, groups will be examined for differences in other baseline characteristics that could 
potentially influence treatment outcome. Any variables that differ between groups and are related to outcome 
measures will be examined as potential covariates in subsequent data analyses. 
Demographic and Baseline Characteristics 
Women, minorities, and children (18-21 years of age) will be included to the extent they are reflected in this 
non-treatment seeking population.  In our previous oxycodone clinical trials, the percentage of females and 
males is approximately 30% and 70% respectively. We will continue recruitment efforts to achieve a 50-50 
balance and thus permit meaningful analyses by sex across groups.  
 
The ethnic representation has been 55% Black, 44% White, 15% Hispanic, and <1% Asian in previous research 
by our group. Nevertheless, we are prepared to implement recruitment procedures to ensure a more diverse 
patient population.  These procedures include: 1) Targeted advertising in newspapers which serve minority 
communities (e.g., Hispanic or Latino communities). 2) Distribution of flyers and notices in neighborhoods 
known to have a high minority population. 3) Engaging in outreach activities on an ongoing basis, e.g., 
contacting church and community leaders in the Hispanic communities to provide educational material about 
oxycodone dependence and its consequences; providing contact information to aid in referrals to our clinic.  
 
Children as defined by NIH (age 18-21years) will be included in this research.  The incidence of severe 
oxycodone abuse/dependence is relatively small in the population of youth less than 18 years old.  From a 
safety perspective, risks of exposure to the proposed study medication and oxycodone administration in 
substance-dependent children under 18 have not been established.  
  
Analysis of Primary Endpoint 
1. Safety: Heart rate (HR), blood pressure (BP), pulse oximetry, pupil diameter, and respiratory rate measures 
during a placebo dose will be compared to these measures after each oxycodone dose (10 mg and 20 mg doses).  
Changes in these measures induced by oxycodone dose along with lorcaserin will be compared to those without 
lorcaserin, by oxycodone dose level (10 mg and 20 mg doses), using repeated measures analysis of variance 
(ANOVA). Adverse event data will be compiled for lorcaserin and placebo cohorts and presented as summary 
statistics.  
2. Oxycodone PK: Plasma concentration-time profiles of oxycodone after oxycodone doses during placebo 
administration (Day zero) will be analyzed to obtain pharmacokinetic parameter estimates of oxycodone (Tmax, 
AUC, apparent t½, CL) by individual. These parameters will be compared within subjects on sessions with 
lorcaserin (Day 5). 
3. Subjective response to oxycodone: Subjective response measures (VAS, CPT) after oxycodone 
administration on day zero will be compared to VAS, CPT measures after oxycodone administration on day 4 
between lorcaserin and placebo treated subjects to determine the extent to which these measures are modified 
by the administration of lorcaserin using repeated measures ANOVA. 
Analysis of Secondary Endpoints 


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1. Response inhibition: Commission errors on the IMT/DMT will be compared between lorcaserin and 
placebo subjects to determine the extent to which this measure is modified by the administration of 
lorcaserin using repeated measures ANOVA. 
2. Craving as measured by the opioid craving scale and brief substance craving scale will be compared 
between lorcaserin and placebo subjects to determine the extent to which this measure is modified by the 
administration of oxycodone and lorcaserin using repeated measures ANOVA. 
 
Safety and tolerability data will be summarized by treatment group.   
Adverse event rates will be coded by body system and MedDra classification term.  Adverse events will be 
tabulated by treatment group and will include the number of patients for whom the event occurred, the rate of 
occurrence, and the severity and relationship to study drug.   
Interim Analysis 
When approximately 50% of patients have completed the study, an interim analysis for safety will be conducted 
by the DSMB. Serious adverse events will be monitored by the committee on an ongoing basis throughout the 
study. 
Sample Size and Randomization 
Rationale for sample size: Sample size for effect of lorcaserin on oxycodone self-administration was based on 
previous research showing effects of oxycodone on pain and subjective responses in an experimental laboratory 
session (Jones et al., 2016). In an effort to increase the power of the study, a Bayesian approach will also be 
utilized that incorporates information from previous studies.  This approach will use a Bayesian hierarchical 
model with subject at the lowest level of the hierarchy and treatment group at the second level.  This model is 
analogous to the repeated measures ANOVA except that prior information will be introduced.  Since many 
similar studies have been conducted with oxycodone users and the same outcome measures we will assign an 
informative prior distribution on the control group where the mean and standard deviation are educated guesses 
from the information provided in previous study of Jones et al., (2016).  For the treatment group we will assume 
a priori no change in the mean from the control group and the standard deviation are similar to those as the 
experimental group of the study by Hart et al. (Hart et al., 2008).  The model will be calculated using standard 
Markov Chain Monte Carlo (MCMC) packages such as WinBUGS, OpenBUGS, JAGS or MCMCpack in R.  
Because MCMC sampling techniques are being employed the quality of the samples from the posterior 
distribution will be checked using trace plots, effective sample size, potential scale reduction factor and 
Hellinger distances (for more on Bayesian analyses and MCMC sampling see (Gelman et al., 2013).  As 
necessary techniques such as discarding burn-in samples, thinning and over-disperse starting points will be 
employed in order to obtain a set of samples from the posterior distribution that have an effective sample size of 
10,000 on all parameters.  All inferences will be made from this set of samples from the posterior distribution. 
To calculate the power for the acute effects of the study three analyses are considered using the paired 
differences of subjects at baseline and acute time points.  A two-sample test on the means is performed using: 
Wilcoxon test (non-parametric), T-test (parametric) and a Bayesian (parametric) approach.  While from a 
Bayesian paradigm the notion of power does not exist in the traditional sense, one can create a decision rule and 
loss function in such a way that the associated risk is analogous to the notion of power.  To understand the 
power of each of the methods a Monte Carlo study was performed utilizing 1,000 separate datasets for likely 
effect sizes and sample sizes. 


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The power was calculated as the proportion of datasets in which the test “rejected” the null hypothesis.  The 
table below gives the power for each test across percent change in effect size and control group sample sizes, 
here the treatment group sample size was n2 = 12. Based on the table below, an n of 6 was chosen as the sample 
size for the placebo group. 
 
 
 
DATA COLLECTION, RETENTION AND MONITORING 
Data Collection Instruments 
The Investigator will prepare and maintain adequate and accurate source documents designed to record all 
observations and other pertinent data for each subject treated with the study drug.   
Study personnel at each site will enter data from source documents corresponding to a subject’s visit into the 
protocol-specific paper CRF when the information corresponding to that visit is available.  Subjects will not be 
identified by name in the study database or on any study documents to be collected by the Sponsor (or 
designee), but will be identified by a subject number. 
The Investigator is responsible for all information collected on subjects enrolled in this study.  All data collected 
during the course of this study must be reviewed and verified for completeness and accuracy by the 
Investigator.  
Data Management Procedures 
The data will be entered into a REDCap database.  The Data Management group will be responsible for data 
processing, in accordance with procedural documentation.  Database lock will occur once quality assurance 
procedures have been completed. 
All procedures for the handling and analysis of data will be conducted using good computing practices meeting 
FDA guidelines for the handling and analysis of data for clinical trials. 
Data Quality Control and Reporting 
After data have been entered into the study database, a system of computerized data validation checks will be 
implemented and applied to the database on a regular basis. The study database will be updated in accordance 
with the resolved queries.  All changes to the study database will be documented. 
Archival of Data 
The database is safeguarded against unauthorized access by established security procedures; appropriate backup 
copies of the database and related software files will be maintained.  Databases are backed up by the database 
administrator in conjunction with any updates or changes to the database.   


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At critical junctures of the protocol (e.g., production of interim reports and final reports), data for analysis is 
locked and cleaned per established procedures. 
Availability and Retention of Investigational Records 
The Investigator will make study data accessible to IRB, and Regulatory Agency (e.g., FDA) inspectors upon 
request.  A file for each subject must be maintained that includes the signed Informed Consent, HIPAA 
Authorization and Assent Form and copies of all source documentation related to that subject.  The Investigator 
will ensure the reliability and availability of source documents from which the information on the CRF was 
derived. 
All study documents (patient files, signed informed consent forms, copies of CRFs, Study File Notebook, etc.) 
will be kept secured for a period of six years after study completion and the IND has been discontinued.   
Subject Confidentiality 
In order to maintain subject confidentiality, only a subject number will identify all study subjects on CRFs and 
other documentation submitted to the Sponsor.  In addition, a Certificate of Confidentiality will be obtained 
from NIDA to protect subject confidentiality. 
 
ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS 
The study will be conducted according to the Declaration of Helsinki, Protection of Human Volunteers (21 CFR 
50), Institutional Review Boards (21 CFR 56), and Obligations of Clinical Investigators (21 CFR 312). 
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other records will be 
identified by a coded number and initials only.  All study records will be kept in a locked file cabinet and code 
sheets linking a patient’s name to a patient identification number will be stored separately in another locked file 
cabinet.  Clinical information will not be released without written permission of the subject, except as necessary 
for monitoring by the FDA.  The Investigator must also comply with all applicable privacy regulations (e.g., 
Health Insurance Portability and Accountability Act of 1996, EU Data Protection Directive 95/46/EC). 
Protocol Amendments 
Any amendment to the protocol will be written by the investigator  Protocol amendments cannot be 
implemented without prior written IRB approval except as necessary to eliminate immediate safety hazards to 
patients.  A protocol amendment intended to eliminate an apparent immediate hazard to patients may be 
implemented immediately, provided the IRBs are notified within five working days. 
Institutional Review Boards and Independent Ethics Committees 
The protocol and consent form will be reviewed and approved by the VCU IRB prior to study initiation.  
Serious adverse experiences regardless of causality will be reported to the IRB in accordance with the standard 
operating procedures and policies of the IRB, and the Investigator will keep the IRB informed as to the progress 
of the study.  The Investigator will obtain assurance of IRB compliance with regulations. 
Any documents that the IRB may need to fulfill its responsibilities (such as protocol, protocol amendments, 
Investigator’s Brochure, consent forms, information concerning patient recruitment, payment or compensation 
procedures, or other pertinent information) will be submitted to the IRB.  The IRBs written unconditional 
approval of the study protocol and the informed consent form will be in the possession of the Investigator 
before the study is initiated.   
Protocol and/or informed consent modifications or changes may not be initiated without prior written IRB 
approval except when necessary to eliminate immediate hazards to the patients or when the change(s) involves 
only logistical or administrative aspects of the study.  Such modifications will be submitted to the IRB and 
written verification that the modification was submitted and subsequently approved should be obtained.   
The IRB must be informed of revisions to other documents originally submitted for review; serious and/or 
unexpected adverse experiences occurring during the study in accordance with the standard operating 


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procedures and policies of the IRB; new information that may affect adversely the safety of the patients of the 
conduct of the study; an annual update and/or request for re-approval; and when the study has been completed. 
Informed Consent Form  
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH GCP, US Code of 
Federal Regulations for Protection of Human Subjects (21 CFR 50.25[a,b], CFR 50.27, and CFR Part 56, 
Subpart A), the Health Insurance Portability and Accountability Act (HIPAA, if applicable), and local 
regulations. 
The Investigator will prepare the informed consent form and HIPAA authorization. The written consent 
document will embody the elements of informed consent as described in the International Conference on 
Harmonization and will also comply with local regulations.  
A properly executed, written, informed consent will be obtained from each subject prior to entering the subject 
into the trial.  Information should be given in both oral and written form and subjects must be given ample 
opportunity to inquire about details of the study. A copy of the signed consent form will be given to the subject 
and the original will be maintained with the subject’s records. 
Publications  
The publication or presentation of any study results shall comply with all applicable privacy laws, including, but 
not limited to, the Health Insurance Portability and Accountability Act of 1996.  
 
 
References: 
Baker, J.R., Jatlow, P., McCance-Katz, E.F., 2007. Disulfiram effects on responses to intravenous cocaine 
administration. Drug Alcohol Depend 87, 202-209. 
Cunningham, K.A., Fox, R.G., Anastasio, N.C., Bubar, M.J., Stutz, S.J., Moeller, F.G., Gilbertson, S.R., 
Rosenzweig-Lipson, S., 2011. Selective serotonin 5-HT(2C) receptor activation suppresses the reinforcing 
efficacy of cocaine and sucrose but differentially affects the incentive-salience value of cocaine- vs. sucrose-
associated cues. Neuropharmacology. 
Gelman, A., Carlin, J., Stern, H., Dunson, D.B., Vehtari, A., Rubin, D.B., 2013. Bayesian Data Analysis, Third 
Edition. Chapman and Hall/CRC, Boca Raton, Florida. 
Hart, C.L., Haney, M., Vosburg, S.K., Rubin, E., Foltin, R.W., 2008. Smoked cocaine self-administration is 
decreased by modafinil. Neuropsychopharmacology 33, 761-768. 
Hutcheson, J.D., Setola, V., Roth, B.L., Merryman, W.D., 2011. Serotonin receptors and heart valve disease--it 
was meant 2B. Pharmacol Ther 132, 146-157. 
Jones, J.D., Sullivan, M.A., Manubay, J.M., Mogali, S., Metz, V.E., Ciccocioppo, R., Comer, S.D., 2016. The 
effects of pioglitazone, a PPARgamma receptor agonist, on the abuse liability of oxycodone among 
nondependent opioid users. Physiol Behav 159, 33-39. 
Le Bars, D., Gozariu, M., Cadden, S.W., 2001. Animal models of nociception. Pharmacol Rev 53, 597-652. 
Levin, E.D., Johnson, J.E., Slade, S., Wells, C., Cauley, M., Petro, A., Rose, J.E., 2011. Lorcaserin, a 5-HT2C 
agonist, decreases nicotine self-administration in female rats. J Pharmacol Exp Ther 338, 890-896. 
Manvich, D.F., Kimmel, H.L., Howell, L.L., 2012. Effects of serotonin 2C receptor agonists on the behavioral 
and neurochemical effects of cocaine in squirrel monkeys. J Pharmacol Exp Ther 341, 424-434. 
Moeller, F.G., Schmitz, J.M., Steinberg, J.L., Green, C.M., Reist, C., Lai, L.Y., Swann, A.C., Grabowski, J., 
2007. Citalopram combined with behavioral therapy reduces cocaine use: a double-blind, placebo-controlled 
trial. American Journal of Drug and Alcohol Abuse 33, 367-378. 


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Shram, M.J., Schoedel, K.A., Bartlett, C., Shazer, R.L., Anderson, C.M., Sellers, E.M., 2011. Evaluation of the 
abuse potential of lorcaserin, a serotonin 2C (5-HT2C) receptor agonist, in recreational polydrug users. Clin 
Pharmacol Ther 89, 683-692. 
 


Protocol Number 
Confidential 
 
Version #: 3 
Version Date 03/21/17 
Page 38 of 40 
 
APPENDIX 1.  DETAILED TIMELINE OF MEASURES 
Study Day 
Screening 
-21 to -1 
Baseline 
Day 0 
Study 
Day 1 
Study 
Day 2 
Study 
 Day 3 
Study 
Day 4 
Follow 
Up  
Day 5 
Follow 
Up 
Day 6 
Location 
CARI 
CRSU 
CARI 
CARI 
CARI 
CRSU 
CARI 
CARI 
Procedure 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
Serum Chemistry 
X 
 
 
 
 
 
 
 
Hematology 
X 
 
 
 
 
 
 
 
Admission to Unit 
 
X 
 
 
 
X 
 
 
Discharge from 
Unit 
 
X 
 
 
 
X 
 
 
History, Physical 
Exam, and 
Neurological 
Exam 
X 
 
 
 
 
 
 
 
Urine Pregnancy 
test (females) 
X 
X 
X 
X 
X 
X 
X 
X 
Psychiatric 
Interview (SCID) 
X 
 
 
 
 
 
 
 
Psychiatric 
Interview (SCID-
II) 
X 
 
 
 
 
 
 
 
Psychiatric 
Interview (KID-
SCID) 
X 
 
 
 
 
 
 
 
Kreek-McHugh-
Schluger-Kellogg 
scale (KMSK) 
X 
 
 
 
 
 
 
 
Fagerstrom Test 
for Nicotine 
Dependence 
(FTND) 
X 
 
 
 
 
 
 
 
National Adult 
Reading Test 
(NART) 
X 
 
 
 
 
 
 
 
Addiction Severity 
Index (ASI-lite) 
X 
 
 
 
 
 
 
 


Protocol Number 
Confidential 
 
Version #: 3 
Version Date 03/21/17 
Page 39 of 40 
 
Brief Substance 
Craving Scale 
X 
X 
X 
X 
X 
X 
X 
X 
Opioid Craving 
Scale (OCS) 
X 
X 
X 
X 
X 
X 
X 
X 
Timeline Follow 
Back Opiate Use 
X 
 
 
 
 
 
 
X 
Drug Use History 
X 
 
 
 
 
 
 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Opiate 
Withdrawal Scale 
(COWS) 
X 
X 
X 
X 
X 
X 
X 
X 
Subjective Opiate 
Withdrawal Scale 
(SOWS) 
X 
X 
X 
X 
X 
X 
X 
X 
Urine drug screen 
X 
X 
X 
X 
X 
X 
X 
X 
Breathalyzer 
X 
X 
X 
X 
X 
X 
X 
X 
Verify Inclusion & 
Exclusion 
X 
X 
 
 
 
 
 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG 
(baseline 
triplicate) and 
singlet thereafter) 
X 
X 
 
 
 
X 
 
 
Brief Physical 
Exam 
 
X 
 
 
 
X 
 
X  
Oxycodone 
Administration for 
3 Doses 
 
X 
 
 
 
X 
 
 
Continuous pulse 
oximetry and 
physiological 
monitoring 
 
X 
 
 
 
X 
 
 
Cold Pressor Test 
(CPT) 
 
X 
 
 
 
X 
 
 
Pupil 
Measurement 
 
X 
 
 
 
X 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 


Protocol Number 
Confidential 
 
Version #: 3 
Version Date 03/21/17 
Page 40 of 40 
 
Inventory 
Visual Analog 
Scale (VAS) 
 
X 
 
 
  
X 
 
 
Profile of Mood 
States (POMS) 
X 
X 
X 
X 
X 
X 
X 
X 
Delayed Memory 
Task (DMT) 
 
X 
 
 
 
X 
 
 
Immediate 
Memory Task 
(IMT) 
 
X 
 
 
 
X 
 
 
Delay Discounting  
Task 
 
X 
 
 
 
X 
 
 
Clinical Global 
Impression 
Severity & 
Improvement 
(CGI-S&I) ( 
baseline CGI-S, 
and CGI-I 
thereafter) 
X 
X 
X 
X 
X 
X 
X 
X 
Columbia Suicide 
Severity Rating 
Scale (C-SSRS) 
(Lifetime version 
at screening and 
since last visit 
version thereafter) 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Draw for 
Oxycodone PK 
 
X 
X 
 
 
X 
X 
 
Blood Draw for 
Lorcaserin PK 
measurement 
 
 
 
 
 
X 
X 
 
Lorcaserin or 
Placebo 
 
X 
X 
X 
X 
X 
 
 
 

ICF_000.pdf: 
 
 
Title: Phase I Drug Interaction and Subjective Effects of Compounds for Opioid Use Disorder 
 
NCT #: NCT03143855 
 
Document approval date: 03/07/2018 
 
Document Type: Informed Consent Form 
 
 
 


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02/19/2018 
 
 
1
 
 
 
RESEARCH PARTICIPANT INFORMATION AND CONSENT FORM 
 
TITLE: Phase I Drug Interaction and Subjective Effects of Compounds for Opioid 
Use Disorder 
 
VCU IRB PROTOCOL NUMBER: HM20008062 
 
INVESTIGATOR: Dr. F. Gerard Moeller 
 
Study Sponsor: National Institute on Drug Abuse (NIDA) 
 
If any information contained in this consent form is not clear, please ask the study 
doctor or the study staff to explain any information that you do not fully understand. 
You may take home an unsigned copy of this consent form to think about or discuss with 
family or friends before making your decision. 
 
INVITATION TO TAKE PART 
You are invited to take part in a research project called “Phase I Drug Interaction 
and Self Administration Studies of Compounds for Opioid Use Disorder” 
conducted by Dr. F. Gerard Moeller, of Virginia Commonwealth University (VCU) 
School of Medicine. For this research project, he will be called the Principal 
Investigator or PI. 
We are inviting you as a person who has been using opioids to take part in this 
clinical research study to look at the interaction between a medication (lorcaserin, trade 
name Belviq) and opioids. At some point during the study you will be given an inactive 
placebo while at other points during the study you may be given lorcaserin. We ask you 
to please read this form carefully.  
 
PURPOSE OF THE STUDY 
The main purpose of this investigational study is to find out how the medication 
lorcaserin reacts with oxycodone and the effects of lorcaserin on how oxycodone makes a 
person feel. Lorcaserin is a medicine that is approved by the FDA for the treatment of 
obesity under the trade name Belviq. Oxycodone is a medicine that is approved by the 
FDA for the treatment of pain under a variety of trade names including OxyContin and 
OxyIR. More information about how lorcaserin reacts with oxycodone may be helpful to 
develop new treatments for addiction to oxycodone and other opioids. The study will 
enroll a total of 72 people all at VCU.  
 
PROCEDURES 
 
If you decide to be in this research study, you will be asked to sign this consent form 
after you have had all your questions answered. 
 
Your participation in this study will last up to 28 days (including intervening weekends). 
 
You are either currently enrolled or have already completed the primary eligibility 
screening procedure as per the screening protocol (HM20000294) and have potentially 
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2
qualified to participate in this study . If needed, you may have up to 2 additional visits 
lasting approximately 1 hour each at CARI before your first hospital day in order to 
confirm study eligibility.   
After you complete the screening, we will review the test results and tell you if you 
qualify for continued study participation.  If you live more than 20 miles from VCU, you 
may stay overnight during the screening at a nearby hotel at no cost to you (we will make 
the hotel arrangements for you).   
 
 
 
The study will consist of one hospital day at the Clinical Research Services (CRS) 
unit at VCU Medical Center, three days at the Collaborative Advanced Research Imaging 
(CARI) facility, and another hospital day at the CRS. There will also be two follow-up 
visits at the CARI facility. The first hospital visit at the CRS will last about 10 hours. 
After the first visit in the hospital you will have three visits at the CARI facility which will 
last around two hours each. The next day after the last visit to the CARI facility you will 
have a second hospital visit that will last about 10 hours, just like the first hospital visit. 
When you arrive at the CRS unit, you will be asked to shower and change into hospital 
scrubs.  Your street clothes and personal belongings (including your cell phone), will be 
collected from you and stored in a secured area for safekeeping until you leave the unit.  
We ask that you leave any valuables at home prior to your CRS visit. Visitors will not be 
allowed during either of your hospital visits, and you must remain on the unit at all times 
during your visit. If you leave the unit before the end of the visit this will lead to you being 
dropped from the research study. VCU is a non- smoking campus, so no tobacco products 
will be allowed. If you are a tobacco user, we can provide you with a nicotine patch at a 
dose based on the amount of cigarettes you typically smoke per day.   
 
During each hospital visit, you will be asked to provide a urine sample for 
complete drug screen analysis, and a breath sample to screen for alcohol. If you are a 
woman, you will also be asked to provide a urine sample for a pregnancy test. Before 
starting any of the study drug procedures, you will get a physical exam, a heart test 
(electrocardiogram (ECG)) where electrodes are placed on you to measure the electrical 
activity of your heart, and be placed on monitors to continuously measure your blood 
oxygen level.  You will then have a catheter (tube) inserted in a vein in your arm. At 
each visit a total of 9 blood samples (4 mL each, which equals approximately 1 
teaspoon) will be drawn from an arm vein in order to check the amount of medication in 
your blood. The maximum total amount of blood that will be drawn during this study 
will be no more than 124 mL, which equals approximately 8 tablespoons. During each 
visit, you will also be given three doses of oxycodone (by mouth) and one of the 
following study medications to take by mouth at 8:00 a.m.; lorcaserin (10 mg); or 
Placebo (inactive pill). You will complete some questionnaires that ask about things like 
recent drug and alcohol use, cravings, and your mood, whether you have had any self- 
harm thoughts, and whether you have experienced any side effects. You will also be 
asked to complete some computer tasks of memory and attention, and also a computer 
task on how the oxycodone makes you feel. You will also have some tests of how 
oxycodone affects pain responses, which will be measured by your placing your hand in 
a container of cold water. At the end of each hospital visit, you will have a test of your 
coordination and you will be provided transportation home by taxi. 
 
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3
On the days you come to the CARI facility you will be given a dose of lorcaserin 
(10 mg); or Placebo (inactive pill). You will be given a dose of medication to take in the 
evening when you are at home. The medication you receive will be assigned randomly; 
that means the decision is made “by chance”, like the flip of a coin.  Using the active 
study medication or placebo will test whether the medication really works.  Urine samples 
will also be tested daily for drugs, and breath samples to screen for alcohol.  If you are a 
woman, your daily urine sample will also be used for a pregnancy test. You will also be 
asked to complete some forms about how you have been feeling and your mood.  
 
You will be asked to complete two follow-up visits after the last visit to the 
hospital.  The first visit will take place three days after your hospital stay has been 
completed, and the second visit will occur a week later.  On each day, you will be asked 
to provide a urine sample for complete drug screen analysis, a blood sample for study 
drug analysis, and a breath sample to screen for alcohol. If you are a woman, your urine 
will also be used for a pregnancy test. You will get a physical exam, and will also  
 
 
be asked to fill out forms about how you feel, whether you have had any self-harm 
thoughts, and whether you have experienced any side effects. At the end of the second 
follow-up visit, you will also meet with the study investigator for a brief discussion about 
your study participation, and final instructions prior to completing the study. 
 
If you live more than 20 miles from VCU, hotel accommodations can be provided at no 
cost to you during each of your study visits (we will make hotel arrangements for you). 
You will also be provided meals, and transportation to and from the hospital each day.    
 
TIME COMMITMENT 
The study elements and time are (see table below for schedule of activities): 
1. Additional screening If needed you may have up to 2 additional visits of about 1 hours 
each at CARI before your first hospital day in order to confirm that you are eligible to 
participate in the study. 
2.   Hospital Day 0 (about 10 hours total time for the this day) 
3.   Outpatient CARI days 1-3: (about 2 hours each visit) 
4.   Hospital Day 4 (about 10 hours total time for this day) 
5.   Outpatient CARI days 5 and 6: Follow-up visit to the CARI for final checkup and 
testing (about 2 hours each) 
The total maximum number of hours is about 46 hours spread over a maximum of 28 
days. 
 
Schedule of Study Activities 
Visit 
Baseline 
Day 0 Week 1 
Day 1 Week 2 
 
Day 2 Week 2 
Day 3 Week 2 
Day 4 Week 2 
Day 5 Week 2 
Day 6 Week 3 
Where 
CRSU 
CARI 
CARI 
CARI 
CRSU 
CARI 
CARI 
Time 
required 
10 hours 
2 hours 
2 hours 
2 hours 
10 hours 
2 hours 
2 hours 
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4
 
Activities 
Urine 
collection 
Vital signs 
Study drug 
dispensed 
Blood draws 
ECG 
Cold water test 
Memory tasks 
Choice Tasks 
Questionnaires 
Urine 
collection 
Vital Signs 
Study drug 
dispensed 
Blood draws 
Questionnaires 
Urine 
collection 
Vital signs 
Study drug 
dispensed 
Questionnaires 
Urine 
collection 
Vital signs 
Study drug 
dispensed 
Questionnaires 
Urine 
collection 
Vital signs 
Study drug 
dispensed 
Blood draws 
ECG 
Cold water test 
Memory tasks 
Choice Tasks 
Questionnaires 
Follow-up for 
side effects 
Urine 
collection 
Vital signs 
Blood draws 
Questionnaires 
Choice Tasks 
 
Follow-up for side 
effects 
Urine collection 
Vital signs & ECG 
Questionnaires 
 
RISKS AND DISCOMFORTS 
 
There are two kinds of risks; one is physical and the other is psychological 
(mental). The most common side effects of lorcaserin include headache, dizziness, 
fatigue, nausea, dry mouth, drowsiness, and constipation. Possible but uncommon side 
effects of lorcaserin include: a prolonged (more than 4 hours) painful erection (priapism), 
dry mouth, flushed dry skin, increased hunger, increased thirst, increased urination, 
itching, redness or swelling of the eye or eyelid, loss of consciousness, severe skin rash or 
hives, stomachache, sweating, tingling of the hands or feet, trouble with breathing, 
trouble with  
 
 
sleeping, vomiting, and unexplained weight loss. 
 
The risks of combining oxycodone and lorcaserin have not been studied in humans, 
although a study in rats did not find any additional dangers in the dosages that will be used 
in this study from opioids alone. However, there are potentially unknown risks of 
combining these two medications including the theoretical possibility of symptoms of 
serotonin syndrome (fever, agitation, confusion, rapid heart rate and high blood pressure), 
although this has never been reported. 
 
The most common side effects of oxycodone are constipation, nausea, stomach pain, 
loss of  
appetite, and vomiting, and other symptoms including somnolence (sleepiness), 
dizziness, itching, headache, dry mouth, sweating, and decreases in the ability to feel 
pain. Possible but uncommon side effects of oxycodone include low blood pressure, and 
loss of consciousness leading to reduced breathing, which can be dangerous if not treated. 
Since you currently use opioids, these side effects are  
less likely, but not impossible. Possible side effects will be monitored carefully through 
blood pressure and breathing monitoring and a form that you fill out each day. The risks 
of combining oxycodone and lorcaserin have not been studied in humans, although both 
oxycodone and lorcaserin are being prescribed and there are no reports of any 
interactions between these medications. However, there are potentially unknown risks of 
combining these two medications. You will be provided with copies of the package 
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5
inserts for both lorcaserin and oxycodone which contain detailed prescribing information 
and a complete listing of potential side effects. For additional information you can 
consult the FDA database online at 
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.  
 
In order to test effects of lorcaserin and oxycodone on pain, you will have several 
tests that involve placing your hand in a container of ice water. This may be 
uncomfortable but you can remove your hand from the water when it becomes too 
uncomfortable for you. 
 
The possible psychological effects of lorcaserin and oxycodone are changes in 
mood or behavior.  We will ask you about your mood during the study and you should 
tell us if you are having any changes in your mood or thoughts of self-harm. Some of 
these questions will be about drug and alcohol use, sex, possible mental health problems, 
legal problems, or your family. You may be uncomfortable because of some of the 
questions that are asked during the interviews, but you have the right to refuse to answer 
any questions. You may feel uncomfortable when providing blood and urine samples and 
breath tests.  If you are a smoker, you may also feel uncomfortable not being able to 
smoke during your hospital stays.  To help relieve any discomfort from nicotine 
withdrawal, we can provide you with a nicotine patch dosed based on the amount of 
cigarettes you smoke per day. A television will be available in your room for 
entertainment, and a telephone will also be available for local calls. 
 
Risks of Cocaine exposure: Medical complications that have been reported with cocaine 
use include heart attack, rupture of major blood vessels, stroke, difficulty breathing, 
swelling, cessation of bowel function, and death. Cocaine is a potent sympathomimetic 
and has been associated with adverse cardiovascular events, including myocardial 
infarction and stroke, when taken illicitly.  
 
Risks of Lorcaserin Combined with Cocaine 
In a recent NIDA funded preclinical study (NIDA Study Report 1812-12132, Sep. 20, 
2013), lorcaserin was administered to rodents in combination with cocaine without any 
significant toxicity.  
 
 
 
However, at 5-fold higher doses (i.e., 25 mg/kg in rats, equivalent to 100 mg/day in 
humans – substantially beyond what is used illicitly), there are indications of increased 
sensitivity to cocaine-induced convulsions due to lorcaserin. The combination of lorcaserin 
and cocaine is currently being studied in our active study (HM20003768- Phase I drug 
interaction and self-administration studies of compounds for Cocaine Use Disorder 
COCUD), which has found no risks associated with combined lorcaserin and cocaine use 
to-date. Further, lorcaserin is FDA approved and widely marketed for the treatment of 
obesity, and no adverse events have been reported to the FDA regarding lorcaserin in 
conjunction with illicit cocaine use.  
 
Risks of positive urine drug screen: 
Possible psychological effects of the urine drug screen are that you may be 
uncomfortable because of a positive drug test. If known to employers or insurance 
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6
companies, the results of urine drug screen might affect a person's ability to obtain a job 
or health or life insurance.  However, data is being collected only for research purposes. 
Your data will be identified by ID numbers assigned to you by our study staff (not 
names), and stored separately from medical records in a locked research area. All 
personal identifying information will be kept in password protected computer files. 
Access to all data will be limited to study personnel. A data and safety monitoring plan is 
established. To help us protect your  
 
 
privacy, we have obtained a Certificate of Confidentiality from the National Institutes of 
Health (see Confidentiality section below). 
 
Special note to women: Additional risks to an unborn child may exist with study 
medications. Therefore, pregnancy testing will be done every day during the study. 
Women of childbearing potential must not be pregnant or breast feeding, and if sexually 
active, must be using acceptable methods of birth control to be enrolled in the study. 
Acceptable methods include: 
a)  Oral contraceptives 
b)  Barrier plus spermicide 
c)  Hormonal or surgical implants 
 
 
Special note to men: Because of possible unknown risks of the study medication on 
reproduction, male subjects will be advised during the study to use a condom when 
having sex. 
Risks associated with having an ECG include: psychological discomfort in learning 
of a potential health condition and the potential for hair removal where the ECG lead is 
applied to the chest. Some individuals who have allergies to tape adhesive may have a 
mild allergic reaction to the ECG adhesive. 
 
Risks associated with the blood draws:  You may have some pain and a bruise when 
the blood is drawn and at the location on your arm where the IV is placed. You will have 
your IV catheter replaced every day hours. There is also a slight chance of infection. 
 
You will be asked to leave the study if you do not follow the study rules or complete 
the requirements and fulfill your responsibilities to complete the study visits, give urine 
or breath samples, or complete forms.  It may also be necessary for you to leave this 
study if you have other problems or illness during the study.  If this happens, appropriate 
referrals will be given. 
USE AND DISCLOSURE OF PROTECTED HEALTH INFORMATION 
Authority to Request Protected Health Information 
The following people and/or groups may request my Protected Health Information: 
• Health Care Providers at the VCUHS 
• Principal Investigator and Research Staff 
• Study Sponsor 
• Research Collaborators 
• Data Coordinators 
• Institutional Review Boards 
• Data Safety Monitoring Boards 
• Government/Health Agencies 
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7
• Others as Required by Law 
 
Authority to Release Protected Health Information 
The VCU Health System (VCUHS) may release the information identified in this 
authorization from my medical records and provide this information to: 
• Health Care Providers at the VCUHS 
• Principal Investigator and Research Staff 
• Study Sponsor 
• Research Collaborators 
• Data Coordinators 
• Institutional Review Boards 
• Data Safety Monitoring Boards 
• Government/Health Agencies 
• Others as Required by Law 
 
 
Once your health information has been disclosed to anyone outside of this study, the 
information may no longer be protected under this authorization. 
 
Type of Information that may be Released 
The following types of information may be used for the conduct of this research: 
   Complete health record 
 
 
Expiration of This Authorization 
 
 This authorization will expire when the research study is closed, or there is no need to 
review, analyze and consider the data generated by the research project, whichever is 
later. 
 This research study involves the use of a Data or Tissue Repository (bank) and will 
never expire. 
  Other (specify):  
 
 
Right to Revoke Authorization and Re-disclosure 
You may change your mind and revoke (take back) the right to use your protected health  
 
information at any time. Even if you revoke this Authorization, the researchers may still 
use or disclose health information they have already collected about you for this study.  If 
you revoke this Authorization you may no longer be allowed to participate in the research 
study.  To revoke this Authorization, you must write to the Principal Investigator, Dr. F. 
Gerard Moeller at 203 East Cary St., Suite 202, Richmond, VA 23219. 
 
 
 
 
BENEFITS TO YOU AND OTHERS 
The benefit you can expect as a result of taking part in this study is information 
regarding your physical and mental health status learned during the screening procedures. 
It is also possible that information will be learned about how lorcaserin affects how 
people feel about opioids, which may help develop new treatments for drug abuse in the 
future. 
 
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COSTS 
All medical tests, hospital stays, and study drug will be offered at no cost to you.  
 
 
PAYMENT FOR PARTICIPATION 
You will be compensated $25 for each of the 1-2 additional eligibility confirmation 
visits (if needed). You will be compensated $150 for each of the 2 hospital days, and an 
additional $20 for each of the visits at the CARI clinic between and after the hospital stays 
for a total of $400 for two hospital days and 5 clinic visits.  If you complete the entire 
study as per specified procedures, you will receive up to  $450 dollars. Payment will be 
dispensed as follows:   
You will receive $25 for each eligibility confirmation visit needed (up to 2), and 
compensated at the end of each visit.  
You will receive $50 for the first hospital stay right after you complete your first 
hospital day.   
 
You will receive $20 for each of the CARI clinic visits completed between hospital 
stays (up to $100 total for completing all five visits),  
After your second hospital stay you will receive $100.  
You will receive the final payment ($150) after your final follow-up visit.  
 
Participants traveling more than 20 miles to VCU will be reimbursed for their travel 
expenses (mileage only at the current VCU rate), and hotel accommodations. Meals will 
also be made available to all participants for each of the study visits if timing of your 
study visit would make it difficult for you to eat on your own. 
All compensation will be provided in the form of cash and or checks (that will be mailed 
to you).  
 
If you are dropped early or choose to withdrawal from the study before 
completing it, you will receive a prorated portion of the compensation, based on the study 
activities you completed. Total payments within one calendar year that exceed $600 will 
require the University to annually report these payments to the IRS and you.  This may 
require you to claim the money you receive for participation in this study as taxable 
income.  VCU is required by federal law to collect your social security number.  Your 
social security number will be kept confidential and will only be used to process payment. 
If you receive payment for taking part in this study please be informed that you 
will be asked to complete a W-9 form that will be forwarded to the accounting 
department as a requirement by the Internal Revenue Service. You will also be issued a 
1099-Misc form from this study for tax reporting purposes. 
 
 
 
ALTERNATIVE TREATMENT 
This study is not intended to treat any medical condition. The alternative to taking part in 
this study is to not take part. 
 
CONFIDENTIALITY 
It will be noted in your protected electronic medical record at VCU Health System 
that you are in this clinical trial. Information about the study including any medications 
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other than the study medications you may receive will be noted in the record. This 
information is protected just as any of your other medical records are protected. The 
name of the study medication will not be in the electronic medical record. It will be listed 
as an investigational medication. 
  Your research data will be identified by ID numbers, not names, and stored 
separately from medical records in a locked research area. All personal identifying 
information will be kept in password protected files and these files will be deleted at the 
end of 6 years. Other study records will be kept in a locked file cabinet for 6 years after 
the study ends and will be destroyed at that time.  Access to research data will be limited 
to study personnel. A data and safety monitoring plan has been established.  
  VCU and the VCU Health System have established secure databases to help with 
monitoring and oversight of clinical research. Your information may be maintained in 
these databases but are only accessible to individuals working on this study or 
VCU/VCUHS officials who have access for specific research related tasks. Identifiable 
information in these are not released outside VCU unless stated in this consent or 
required by law. Personal information about you might be shared with or copied by 
authorized officials of the Federal Food and Drug Administration or the Department of 
Health and Human Services. 
 
We will not tell anyone the answers you give us. But, if you tell us that you intend to 
hurt yourself or someone else, the law says that we have to let people in authority 
know so they can protect you and others. 
  To help us protect your privacy, we will obtain a Certificate of Confidentiality 
from the National Institutes of Health. With this Certificate, the researchers cannot be 
forced to give out information that would identify you, even by a court subpoena, in any 
federal, state, or local civil, criminal, administrative, legislative, or other proceedings. 
The researchers will use the Certificate to resist any demands for information that would 
identify you, except as explained. 
 The Certificate cannot be used to resist a demand for information from employees 
of the United States Government that is used for auditing or evaluation of federally 
funded projects or for information that must be given in order to meet the requirements 
of the federal Food and Drug Administration (FDA). You should understand that a 
Certificate of Confidentiality does not prevent you or a member of your family from 
voluntarily giving information about yourself or your involvement in this research. If an 
insurer, employer, or other person obtains your written consent to receive research 
information, then the researchers may not use the Certificate to withhold the information. 
The Certificate of Confidentiality does not prevent the researchers from disclosing 
voluntarily, without your consent, information that would identify you as a participant in 
the research project under the following circumstances, child abuse, elder abuse, the 
intent to hurt self or others, or required reportable communicable diseases, such as HIV. 
No one outside the research staff may call and get information about you.  If you 
decide you would like copies of your medical test results, you may sign a form to release 
information to you or your physician. Only specific medical information, not research 
information, will be released. 
 
You will not be personally identified in any reports or publications that may result 
from this study.  Any personal information about you that is gathered during this study 
will remain confidential to every extent of the law.   
A description of this clinical trial will be available on 
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http://www.ClinicalTrials.gov as required by U.S. Law.  This website will not include 
any information that can identify you. At most the website will include a summary of 
the results.  You can search this website at any time. 
 
COMPENSATION FOR INJURY or ILLNESS 
If you suffer any injury as a result of taking part in this research study, please 
understand that nothing has been arranged to provide free treatment of the injury or any 
other type of payment. However, all needed facilities, emergency treatment and 
professional services will be available to you, just as they are to the community in 
general. You should report any injury to Dr. Moeller at (804) 828-3810 (daytime) or 
(804) 828-0951 (after hours emergency paging). You will not give up any of your legal 
rights by signing this consent form. 
Fees for such treatment may be billed to you or to appropriate third party 
insurance. Your health insurance company may or may not pay for treatment of injuries 
or illness as a result of your participation in this study. 
To help avoid research-related injury or illness it is very important to follow all 
study directions. 
 
VOLUNTARY PARTICIPATION AND WITHDRAWAL 
Your decision to take part is voluntary and you may refuse to take part, or choose to 
stop taking part, at any time.  A decision not to take part or to stop being a part of the 
research project will not change the services that are available to you from the research 
clinic or Virginia Commonwealth University School of Medicine. You do not have to 
take part in this study to take part in other research studies in the clinic. Your decision to 
withdraw will involve no penalty or loss of benefits to which you are otherwise entitled. 
You may refuse to answer any questions asked or written on any forms, however 
answering some questions about your health and safety are necessary to take part in this 
study. 
Your participation in this study may be stopped at any time by the study doctor or 
the sponsor without your consent. The reasons might include: 
• 
 the study doctor thinks it necessary for your health or safety; 
• 
 you have not followed study instructions; 
• 
 the sponsor has stopped the study;  
• 
 administrative reasons require your withdrawal. 
 
QUESTIONS 
The investigators of this study will be glad to answer any further questions at any 
time.  In the event of problems due to this study you should report them to Dr. Moeller at 
(804)828-3810. If you would like to withdraw your permission to use blood or tissue 
samples, mail address for sending a letter notifying us to 203 East Cary Street, Suite 202, 
Richmond, VA 23219. 
 
If you have general questions about your rights as a participant in this or any other 
research, you may contact: 
 
Office of Research 
Virginia Commonwealth University 
800 East Leigh Street, Suite 3000 
P.O. Box 980568 
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Richmond, VA 23298 
Telephone: (804) 827-2157 
 
Contact this number for general questions, concerns, or complaints about 
research. You may also call this number if you cannot reach the research team or if you 
wish to talk to someone else. General information about participation in research studies 
can also be found at http://www.research.vcu.edu/irb/volunteers.htm. 
Do not sign this consent form unless you have had a chance to ask questions and 
have received satisfactory answers to all of your questions. 
 
 
CONSENT 
I have been provided with an opportunity to read this consent form carefully. All of the 
questions that I wish to raise concerning this study have been answered. 
By signing this consent form, I have not waived any of the legal rights or benefits, 
to which I otherwise would be entitled.  My signature indicates that I freely consent to 
participate in this research study.  I will receive a copy of the consent form once I have 
agreed to participate. 
 
 
 
 
Participant Name, (Printed) 
 
 
 
 
Participant Signature 
Date 
 
 
 
 
Name of Person Conducting Informed Consent Discussion / Witness (Printed) 
 
 
Signature of Person Conducting Informed Consent 
Date 
Discussion / Witness 
 
 
 
 
Principal Investigator Signature (if different from above) 
Date 
 
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