Treatment With Lorcaserin for Cocaine Use: The TLC Study
Phase: PHASE2
Conditions: Cocaine Use Disorder
Sponsor: Glenn-Milo Santos

PI: Santos, Glenn-Milo 
Confidential 
 
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University of California, San Francisco 
Clinical Research Protocol 
The TLC Study:  Treatment with Lorcaserin for Cocaine Use 
Protocol Number: 
17-21502 
Version Date: 
7/22/2017 
Investigational Product: 
BELVIQ® XR (lorcaserin) 
IND Number: 
134951 
Development Phase: 
Phase II 
Sponsor: 
Glenn-Milo Santos, PhD, MPH 
University of California at San Francisco 
Department of Community Health Systems 
School of Nursing 
2 Koret Way, N505 
San Francisco, California 94143-0608 
Funding Organization: 
National Institute on Drug Abuse (NIDA) 
Principal Investigator: 
Name: Glenn-Milo Santos, PhD, MPH 
Telephone:  (628) 217-6231  
E-mail:  Glenn-milo.Santos@ucsf.edu 
 
Medical Monitor: 
Name: Phillip Coffin,  
 
Telephone: (510) 407-2603  
 
 
E-mail:  Phillip.coffin@sfdph.org 
 
Coordinating Center: 
San Francisco Department of Public Health 
Population Health Division 
25 Van Ness Avenue, Suite 500 
San Francisco, California 94102 
 
Approval: 
 
 
 
07-22-2017 
PI or Sponsor Signature (Name and Title)  
 
Date 
This confidential information about an investigational product is provided for the exclusive use of 
investigators of this product and is subject to recall at any time.  The information in this document 
may not be disclosed unless federal or state law or regulations require such disclosure.  Subject to the 
foregoing, this information may be disclosed only to those persons involved in the study who have a 
need to know, with the obligation not to further disseminate this information.   
 

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PROTOCOL AGREEMENT 
 
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include ensuring the safety of the study subjects enrolled under my supervision as outlined in the 
protocol.  It is understood that all information pertaining to the study will be held strictly 
confidential and that this confidentiality requirement applies to all study staff at this site. 
Furthermore, on behalf of the study staff and myself, I agree to maintain the procedures required 
to carry out the study in accordance with accepted GCP principles and to abide by the terms of 
this protocol. 
 
Protocol Number:  17-21502 
 
Protocol Title:  The TLC Study:  Treatment with Lorcaserin for Cocaine Use 
 
Protocol Date:  TBD 
 
 
 
07-22-2017 
Investigator Signature  
 
Date 
Glenn-Milo Santos, Associate Professor 
Print Name and Title 
Site # 
1 
 
Site Name 
San Francisco Department of Public Health 
Address 
25 Van Ness Ave, Suite # 500 
 
San Francisco, CA. 94102 
 
 
 
 
Phone Number 
 

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TABLE OF CONTENTS 
 
1 
BACKGROUND .................................................................................................................. 10 
1.1 
Overview of Clinical Studies ....................................................................................... 10 
2 
STUDY RATIONALE ........................................................................................................ 12 
2.1 
Risk / Benefit Assessment ........................................................................................... 12 
3 
STUDY OBJECTIVES ....................................................................................................... 13 
3.1 
Primary Objective ........................................................................................................ 13 
3.2 
Secondary Objectives .................................................................................................. 13 
4 
STUDY DESIGN ................................................................................................................. 14 
4.1 
Study Overview ........................................................................................................... 14 
5 
CRITERIA FOR EVALUATION...................................................................................... 14 
5.1 
Primary Efficacy Endpoint .......................................................................................... 14 
5.2 
Secondary Efficacy Endpoints ..................................................................................... 14 
5.3 
Safety Evaluations ....................................................................................................... Error! 
Bookmark not defined. 
6 
SUBJECT SELECTION ..................................................................................................... 14 
6.1 
Study Population .......................................................................................................... 14 
6.2 
Inclusion Criteria ......................................................................................................... 14 
6.3 
Exclusion Criteria ........................................................................................................ 15 
7 
CONCURRENT MEDICATIONS .................................................................................... 15 
7.1 
Allowed ....................................................................................................................... 15 
7.2 
Prohibited..................................................................................................................... 15 
8 
STUDY TREATMENTS .................................................................................................... 15 
8.1 
Method of Assigning Subjects to Treatment Groups ................................................... 15 
8.2 
Blinding ....................................................................................................................... 16 
8.3 
Test and Control Formulation ...................................................................................... 16 
8.4 
Supply of Study Medication at the Site ....................................................................... Error! 
Bookmark not defined. 
8.5 
Study Medication Accountability ................................................................................ 18 
8.6 
Measures of Treatment Compliance ............................................................................ 18 
9 
STUDY PROCEDURES AND GUIDELINES ................................................................. 18 
9.1 
Clinical Assessments ................................................................................................... 18 
9.2 
Clinical Laboratory Measurements  ............................................................................. 21 
10 EVALUATIONS BY VISIT ............................................................................................... 21 
10.1 Visit 1 (Screening 1 Visit) ........................................................................................... 21 
10.2 Visit 2 (Screening 2 Visit) ........................................................................................... 22 
10.3 Visit 3 (Enrollment) ..................................................................................................... 22 
10.4 Visit 4 (Weekly Visits) ................................................................................................ 22 
10.5 Visit 5 (Monthly) ......................................................................................................... 23 
10.6 Early Withdrawal Visit ................................................................................................ 23 

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11 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION ........................ 23 
11.1 Adverse Events ............................................................................................................ 23 
11.2 Serious Adverse Experiences (SAE) ........................................................................... 25 
11.3 Protocol Defined Important Medical Findings Requiring Real Time Reporting ........ Error! 
Bookmark not defined. 
11.4 Medical Monitoring ..................................................................................................... Error! 
Bookmark not defined. 
11.5 Safety Management Plan ............................................................................................. 25 
12 DISCONTINUATION AND REPLACEMENT OF SUBJECTS ................................... ERROR! 
BOOKMARK NOT DEFINED. 
12.1 Withdrawal of Subjects ............................................................................................... Error! 
Bookmark not defined. 
12.3 Replacement of Subjects.............................................................................................. Error! 
Bookmark not defined. 
13 PROTOCOL VIOLATIONS .............................................................................................. ERROR! 
BOOKMARK NOT DEFINED. 
14 DATA SAFETY MONITORING– .................................................................................... ERROR! 
BOOKMARK NOT DEFINED. 
15 STATISTICAL METHODS AND CONSIDERATIONS ................................................ ERROR! 
BOOKMARK NOT DEFINED. 
15.1 Data Sets Analyzed ...................................................................................................... Error! 
Bookmark not defined. 
15.2 Demographic and Baseline Characteristics ................................................................. Error! 
Bookmark not defined. 
15.3 Analysis of Primary Endpoint ..................................................................................... 29 
15.4 Analysis of Secondary Endpoints ................................................................................ 30 
15.5 Interim Analysis .......................................................................................................... 30 
15.6 Sample Size and Randomization ................................................................................. 30 
16 DATA COLLECTION, RETENTION AND MONITORING ........................................ 30 
16.1 Data Collection Instruments ........................................................................................ 30 
16.2 Data Management Procedures ..................................................................................... 31 
16.3 Data Quality Control and Reporting ............................................................................ 31 
16.4 Archival of Data .......................................................................................................... 31 
16.5 Availability and Retention of Investigational Records ................................................ 31 
16.6 Monitoring ................................................................................................................... 32 
16.7 Subject Confidentiality ................................................................................................ 33 
17 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS ................... 32 
17.1 Protocol Amendments ................................................................................................. 32 
17.2 Institutional Review Boards and Independent Ethics Committees .............................. 33 
17.3 Informed Consent Form ............................................................................................... 34 
17.4 Publications ................................................................................................................. 34 
17.5 Investigator Responsibilities ........................................................................................ 34 
18 APPENDICES ...................................................................................................................... 36 

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18.1 Study Procedures ......................................................................................................... 36 
18.2 References ................................................................................................................... 36 
 

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LIST OF ABBREVIATIONS 
ACASI 
Audio Computer Assisted Survey Instrument 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BART 
Balloon Analogue Risk Task – impulsivity test 
BMI 
Body Mass Index 
BUN 
blood urea nitrogen 
CBC 
Complete blood count 
CBO 
Community based organization  
CCG 
Community Consulting Group 
CFR 
Code of Federal Regulations 
CRF 
case report form 
CPHR 
Center for public health research 
DMC 
Data Monitoring Committee 
DSMB 
Data Safety Monitoring Board 
DSM-IV 
Diagnostic and Statistical Manual for Mental disorders 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEE 
generalized estimating equations 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
Human Immunodeficiency Virus 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
MM 
Medical Management counseling 
MSM 
Men who have sex with men 
NIAAA 
National Institute on Alcohol Abuse and Alcoholism  
PrEP 
pre-exposure prophylaxis 
PI 
Principal Investigator 
SAE 
serious adverse experience 
SAMHSA 
Substance Abuse and Mental Health Services Administration 
SCID 
Structural clinical interview for DSM disorders 
SFDPH 
San Francisco Department of Public Health 
SMS 
Text message 
TLFB 
Timeline follow-back 

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PROTOCOL SYNOPSIS 
TITLE 
The TLC Study:  Treatment with Lorcaserin for Cocaine Use 
SPONSOR 
Glenn-Milo Santos 
FUNDING 
ORGANIZATION 
NIDA 
NUMBER OF SITES 
1 
RATIONALE 
Lorcaserin’s mechanism of action as a potent 5-HT2CR selective agonist may 
have inhibitory control on DA activity, which may decrease the positive 
rewarding effects of cocaine and lead to reductions in use, while 5-HT2CR 
activation itself may lead to reductions in likelihood of relapse.  There are no 
pharmacological agents available to reduce cocaine use disorder.   
STUDY DESIGN 
This study will enroll 45 actively using Men who have sex with men with 
cocaine use disorders in a placebo-controlled 12-week trial. Individuals will 
be randomly assigned (2:1) to receive 12 weeks of lorcaserin 20mg (n=30) 
or placebo (n=15) to be taken daily in this double-blind trial.  
PRIMARY 
OBJECTIVE 
To establish the feasibility, tolerability, acceptability and adherence of 
enrolling and retaining 45 adults with cocaine use disorders in a 12-week 
randomized, double-blind study of lorcaserin versus placebo. 
 
SECONDARY 
OBJECTIVES 
To evaluate the preliminary efficacy of lorcaserin versus placebo to 
reduce cocaine use and HIV-related sexual risk behaviors among MSM 
with cocaine use disorders, as determined by the proportion of cocaine-
positivity from twice weekly urine samples and self-reported sexual 
behaviors. 
NUMBER OF 
SUBJECTS 
45 
SUBJECT 
SELECTION 
CRITERIA 
Inclusion Criteria:  1) Male gender; 2) self-reported anal intercourse with 
men in the prior six months while under the influence of cocaine; 3) cocaine 
use disorder by DSM-V SCID criteria; 4) current cocaine use confirmed by 
urinalysis and cocaine use at least 1 day in the past 30 days; 5) HIV-negative 
by rapid test or HIV-positive with medical record of HIV infection; 6) no 
current acute illnesses requiring prolonged medical care; 7) no chronic 
illnesses that are likely to progress clinically during trial; 8) able and willing 
to provide informed consent and adhere to visit schedule; 9) age 18–65 
years; 10) baseline CBC, total protein, albumin, glucose, alkaline 
phosphatase, creatinine, BUN, and electrolytes without clinically significant 
abnormalities as determined by study clinician in conjunction with 
symptoms, physical exam, and medical history. 
 
Exclusion Criteria:  1) Any psychiatric condition (e.g., depression with 
suicidal ideation, schizophrenia) or medical condition that would preclude 
safe study participation; 2) HIV-positive test result at screening visit but 
previously unaware of HIV infection (i.e., newly diagnosed with HIV 
infection at screening; those with a medical record of HIV infection are 

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eligible); 3) any moderate to severe alcohol or substance use disorders (other 
than cocaine use disorders), according to DSM-V criteria; 4) known allergy 
or previous adverse reaction to lorcaserin; 5) current CD4 count < 200 
cells/mm3 ;6) severe liver impairment (Child-Pugh score > 9); 7) severely 
impaired renal function (creatinine clearance £ 30 ml/min); 8) use of 
medications that affect the serotonergic neurotransmitter system (e.g., 
selective serotonin reuptake inhibitors (SSRIs), selective serotonin- 
norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, 
monoamine oxidase inhibitors (MAOIs)); 9) predisposition to priapism; 10) 
currently participating in another longitudinal intervention research study; 
11) body mass index (BMI) ≥ 30 with desire to use weight management 
medication, or BMI > 40;12) BMI < 15; 13) anticipated use of agents that 
are associated with valvulopathy and/or pulmonary hypertension 
 
TEST PRODUCT, 
DOSE, AND ROUTE 
OF 
ADMINISTRATION 
BELVIQ® XR (lorcaserin)  20mg., manufactured by: Arena 
Pharmaceuticals: Untere Brühlstrasse 4, 4800 Zofingen, Switzerland 
Product will be administered orally each day for 12 weeks length of time.   
 
CONTROL 
PRODUCT, DOSE 
AND ROUTE OF 
ADMINISTRATION 
Placebo, 20 mg.   
Product will be administered orally each day for 12 weeks length of time.   
DURATION OF 
SUBJECT 
PARTICIPATION 
AND DURATION OF 
STUDY 
Subjects will be on study for up to 12 weeks 
Screening:  up to 4 weeks 
Treatment:  12 weeks 
The total duration of the study is expected to be 16 weeks or 4 months.  1 
month for subject recruitment and 3 months for treatment phase.   
CONCOMMITANT 
MEDICATIONS 
Allowed: standard treatment  
 
Prohibited:  Serotonin reuptake inhibitors (SSRIs), selective serotonin- 
norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, 
monoamine oxidase inhibitors (MAOIs) 
EFFICACY 
EVALUATIONS 
 
PRIMARY ENDPOINT 
In the overall sample of 45, proportions will be estimated with margins of 
sampling error (MSEs; i.e., half widths of 95% confidence intervals) of 
<=14.4 percentage points, and means with MSEs of 0.30 standard 
deviations, both typical for a small pilot study. While the study will only be 
powered to detect large between-group differences in process measures, it 
will provide warning of potential problems. 
 
SECONDARY 
ENDPOINTS 
We will also classify AEs as any AE that results in stopping study 
medication, specific common AEs (>2% in both groups), AEs for general 

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organ system categories, and AEs potentially related to study drug. The 
probability of observing at least one AE with population incidence of 1, 2, 
and 5% in the active arm will be 26, 45, and 70% with 2:1 randomization, 
respectively. 
SAFETY 
EVALUATIONS 
Change in clinical safety labs from baseline to Week 12 
Incidence of adverse events 
PLANNED INTERIM 
ANALYSES  
No planned interim analyses 
STATISTICS 
Primary Analysis Plan 
To establish the feasibility of enrolling and retaining 45 MSM with cocaine 
use disorders in a 12-week 2:1 randomized, double-blind study of lorcaserin 
versus placebo. We will calculate the following feasibility measures: 1) 
proportion of those eligible among those screened; 2) proportion enrolled 
among those eligible; and 3) study completion rate. Process measures (e.g., 
visit length, counseling session completion) and reactions to study 
procedures will also be collected and reported. Between-group differences 
will be assessed using Fisher’s exact and Wilcoxon rank sum tests. We will 
also calculate Kaplan-Meier curves for time to dropout, by group, and test 
for differences using the log-rank test. Precision: In the overall sample of 45, 
proportions will be estimated with margins of sampling error (MSEs; i.e., 
half widths of 95% confidence intervals) of ≤14.4 percentage points, and 
means with MSEs of 0.30 standard deviations, both typical for a small pilot 
study. While the study will only be powered to detect large between-group 
differences in process measures, it will provide warning of potential 
problems. 
To explore the tolerability of lorcaserin versus placebo among MSM with 
cocaine use disorders, as determined by the number of adverse clinical 
events in the cocaine and placebo arms. We will compute the proportions of 
those experiencing adverse events, both overall and by type. Adverse 
clinical events, AEs and SAEs, and other binary safety outcomes will be 
presented as percent of participants that experience the safety outcome by 
treatment assignment. We will also classify AEs as any AE that results in 
stopping study medication, specific common AEs (>2% in both groups), 
AEs for general organ system categories, and AEs potentially related to 
study drug. The probability of observing at least one AE with population 
incidence of 1, 2, and 5% in the active arm will be 26, 45, and 70% with 2:1 
randomization, respectively. 
 To describe the acceptability and adherence for lorcaserin versus placebo 
MSM with cocaine use disorders. We will measure the acceptability of 
lorcaserin compared to placebo among participants through a qualitative 
interview and survey evaluations of the study procedures, study drug 
characteristics, and dosing schedule at the final visit. We will determine 
medication adherence via MEMs Cap data, pill count, and self-report from 
TLFB and SMS texts. Measures of interest will include percent of doses 
taken, patterns of adherence, and time to stopping medication. We will 
assess how these measures of adherence track with patterns of cocaine use as 
measured in TLFB and urinalysis. Concordance of the adherence measures 
will be examined using weighted Kappa and correlations. 

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Rationale for Number 
of Subjects 
 In the overall sample of 45, proportions will be estimated with margins of 
sampling error (MSEs; i.e., half widths of 95% confidence intervals) of 
≤14.4 percentage points, and means with MSEs of 0.30 standard 
deviations, both typical for a small pilot study. While the study will only 
be powered to detect large between-group differences in process 
measures, it will provide warning of potential problems. 
 
 

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1. BACKGROUND 
Lorcaserin, a novel selective serotonin (5-HT) receptor agonist, is a promising agent to treat cocaine use 
disorders. Cocaine use increases dopamine (DA) levels, the neurochemical responsible for the reinforcing 
effects of the drug, and there is compelling data suggesting that the DA system’s activity is modulated by 
the central 5-HT systems.69-71   
 
In particular, the 5-HT2C receptor (5-HT2CR) has been identified as the primary 5-HT receptor subtype 
that inhibits the DA system’s activity.71 5-HT2CR agonists have reduced dopamine release in the nucleus 
accumbens (NAcc) and frontal neurocortex.69,71 Conversely, increased DA release in the NAcc result 
from the blockade of 5-HT2CR.72 
OVERVIEW OF CLINICAL STUDIES 
Cocaine use in the US is an unrelenting public health problem with serious negative medical, societal, 
and economic impacts.
1-3 The US is the world’s largest consumer of cocaine, accounting for nearly 
36% of the total global consumption.
4,5 In both powder and rock 
(i.e., “crack”) form, cocaine is an addictive psychostimulant; it is 
estimated that up to one in six cocaine users may develop 
dependence/moderate-to-severe use disorders.
2,6,7 Cocaine is the 
leading cause of illicit substance–related emergency department 
visits in the US
3 and it is associated with direct cardiac toxicity, 
myocardial infarctions and, sudden cardiac death.
9-13 Cocaine 
use is a significant decrease (test for trend p<0.001)
17,18 in 
methamphetamine use among San Francisco MSM (from 22% to 13%). San Francisco community-
based surveys observed similar trends: cocaine use among MSM increased from 9.6% in 2009 to 
20.4% in 2013.
19,20 Of the estimated 19,657 illicit psychostimulant- using MSM in San Francisco, 
81.3% are cocaine users.16  MSM remain disproportionately impacted by HIV—despite sizable 
efforts to stem the epidemic in this group—accounting for 61% and 90% of new infections in the US 
and San Francisco, respectively.21-24 It is imperative to develop more evidence-based HIV 
interventions for MSM; the National HIV/AIDS Strategy specifically calls for additional interventions 
for this population.
25 Cocaine use is associated with HIV-related sexual risk behaviors in MSM. In 
NHBS, 54% of cocaine users reported having sex while under the influence of cocaine.
14 The acute 
pharmacological effects of cocaine (e.g., altered cognition, impairment of judgment, and increased 
sexual desire and confidence) have been attributed to the association between cocaine use and sexual 
risk behaviors.
26-30 Moreover, a myriad of psychosocial factors (e.g., cognitive escape, impulsivity, and 
expectancies) are thought to account for the link between cocaine use and sexual risks.
31-34 
Furthermore, the bar, club, and circuit-party (weekend-long dance events) settings frequented by MSM 
are environments conducive to both cocaine use and meeting multiple sex partners.
35-37 Indeed, cocaine 
use is independently associated with unprotected anal intercourse, multiple partners, increased duration 
of sex, anonymous partners, sex in a public sex venue, and exchanging money or drugs for sex.
38-43 In 
the Project ECHO study, a large San Francisco study of substance-using MSM conducted by the 
proposed research team, increased frequency of cocaine use was associated with greater HIV-related 
sexual risk; those who reported episodic use (less than weekly) and those with weekly or greater cocaine 
use had 1.86- and 3.13-fold greater odds of HIV serodiscordant unprotected anal intercourse, 

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respectively, compared to non-users.
44 This dose-dependent relationship is consistent with findings 
from a probability sample of HIV-negative MSM; those with cocaine dependence were more likely to 
have high-risk sexual behaviors than their non-dependent counterparts.
41 
Cocaine use has been significantly associated with new HIV infections.45-47 In the EXPLORE 
longitudinal study of 4,295 HIV-negative MSM from six cities, cocaine use was associated with a 2.24-
fold greater hazard for HIV seroconversion.
46 Similarly, in the Multicenter AIDS Cohort Study, use of 
cocaine or other stimulants, alone or in combination with other drugs, was attributed to 37.3% of the 
new HIV infections in the study.
45 In a probability sample of San Francisco MSM, cocaine and other 
stimulant use was also 2.5-fold more common among MSM living with HIV.
48 Among HIV-positive 
individuals, cocaine use was associated with poor adherence to antiretroviral treatment (ART), HIV 
disease progression, lower CD4 count, and higher mortality.
49-52 Weekly cocaine use was associated 
with higher HIV viral load, even after controlling for ART adherence, 
53and in in vitro studies, cocaine 
enhanced HIV viral replication.
54,55 Poor ART adherence and higher HIV viral load among cocaine users 
may potentiate greater risk of HIV transmission.
56 
Innovative treatments for cocaine use disorders are needed for MSM.
57 Because cocaine use is 
common among MSM and is associated with high-risk sexual behavior and HIV infection, 
interventions that can reduce cocaine use are likely to have an impact on reducing the transmission of 
HIV.
28 Current prevention approaches to cocaine use for MSM are therapy and substance use treatment 
programs. However, most substance-using MSM do not access drug treatment, reinforcing the need to 
develop interventions outside of treatment settings.
44,58,59 Furthermore, while some behavioral 
interventions for substance-using MSM report reductions in both substance use and HIV risk 
behaviors,
60,61 behavioral interventions alone have limited efficacy and may benefit from adjuvant 
pharmacologic agents.57,62 However, there are no FDA-approved medications for cocaine use 
disorders, which severely limits treatment options.
63,64 Pharmacologic approaches have been 
successful in treating nicotine, alcohol, and heroin dependence.
65-67 Despite the link between cocaine 
use and HIV risk, the use of pharmacologic interventions to reduce cocaine-related sexual risk 
among MSM remains underexplored. The absence of published studies on efficacious interventions to 
reduce cocaine- related sexual risk behaviors among MSM who have no desire to abstain from cocaine 
presents a major gap in the field of substance use research and HIV prevention. Pharmacotherapy 
for methamphetamine dependence in MSM has shown that reductions in substance use can result in 
parallel reductions in methamphetamine-related sexual risk behaviors among MSM not seeking 
treatment.
68 Pharmacotherapy for cocaine use may lead to an analogous parallel reduction in cocaine-
related sexual risks. 
Lorcaserin, a novel selective serotonin (5-HT) receptor agonist, is a promising agent to treat 
cocaine use disorders. Cocaine use increases dopamine (DA) levels, the neurochemical responsible 
for the reinforcing effects of the drug, and there is compelling data suggesting that the DA system’s 
activity is modulated by the central 5-HT systems.69-71 In particular, the 5-HT2C receptor (5-HT2CR) has 
been identified as the primary 5-HT receptor subtype that inhibits the DA system’s activity.71 5-HT2CR 
agonists have reduced dopamine release in the nucleus accumbens (NAcc) and frontal neurocortex.69,71 
Conversely, increased DA release in the NAcc result from the blockade of 5-HT2CR.72 Furthermore, 

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genetic variations in the 5-HT2CR and its functional status have been associated with vulnerability to 
cocaine cue reactivity—a strong predictor of relapse—and relapse- like behaviors in cocaine dependent 
rodents and humans.73,74 These data lend support to the use of agents that selectively activate the 5-
HT2CR.  We postulate that lorcaserin’s mechanism of action as a potent 5-HT2CR selective agonist 
will have inhibitory control on DA activity, which may decrease the positive rewarding effects of 
cocaine and lead to reductions in use, while 5-HT2CR activation itself may lead to reductions in 
likelihood of relapse. 
Preclinical data support the potential of lorcaserin in reducing cocaine use.
70,75-85 Lorcaserin is 18- and 
120-fold more selective toward the 5-HT2CR compared to 5-HT2A and 5-HT2B receptors, respectively.86 
5-HT2CR selective agonists, including lorcaserin, have been associated with reductions in cocaine self-
administration in mice
87,88 and non-human primates.
84,89 Consistent reductions in cue- and cocaine-
primed drug seeking have resulted from use of 5-HT2CR selective agonists.79,87,90,91 Furthermore, 5-
HT2CR selective agonists have attenuated acute cocaine-induced activity and the development of long-
term cocaine-induced locomotor sensitization.78 Reinstatement studies to model the relapse processes 
have also found that 5-HT2CR selective agonists reduced cocaine seeking behavior, again in both 
rodents 
79,87,91-94 and primates.
84 
Data from other preclinical and clinical studies also support lorcaserin’s potential to treat drug 
disorders. For example, lorcaserin has been shown to reduce nicotine self-administration, 95 as well as 
nicotine discrimination, and cue-induced reinstatement of nicotine seeking.96 Currently, another team 
is evaluating lorcaserin in a placebo-controlled Phase 2, 12-week trial on smoking cessation 
(ClinicalTrials.gov #: NCT02044874). 
 
2. STUDY RATIONALE 
2.1 Study Overview: 
This study will represent the first Phase 2 randomized outpatient clinical trial to evaluate the potential of 
lorcaserin to reduce cocaine use among actively using participants with cocaine use disorders. Although 
there is an ongoing human laboratory study of lorcaserin’s effects on craving and intravenous cocaine self-
administration during overnight confinements at a medical center (ClinicalTrials.gov #: NCT02680288), 
our proposed study will provide distinct yet complementary data on the viability of lorcaserin to reduce 
cocaine. Our study is unique because it involves the outpatient treatment and evaluation of lorcaserin to 
reduce cocaine use and cocaine- associated sexual risk behaviors among men who have sex with men 
over a 12-week follow-up period. Hence, data from this pilot can inform the sample size required for a 
larger clinical efficacy trial of lorcaserin for outpatient treatment of cocaine use. Additionally, this study 
will determine if lorcaserin is a feasible, tolerable, and acceptable option for cocaine outpatient treatment. 
 
2.2  Risk / Benefit Assessment 
Lorcaserin is an FDA-approved medication that is well-tolerated with relatively few adverse 
events (AEs).
103 Three Phase 3 trials (cumulative N=7789) that evaluated lorcaserin’s treatment effect 
on obesity have established its safety among patients with and without diabetes.
104-107 The most 

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common reported side effects for lorcaserin include headaches, dizziness, fatigue, nausea, dry mouth, 
and constipation.
104-107 In these trials, 8.6% of individuals given lorcaserin discontinued treatment as a 
result of AEs, compared to 6.7% individuals given placebo.
104-107 Aside from pregnancy, there are no 
contraindications for lorcaserin.
104 Nevertheless, the safety and tolerability of lorcaserin among active 
cocaine users is unknown. Lorcaserin has a low potential for abuse.
108 The frequency of AEs 
associated with lorcaserin increases when taken above the therapeutic dose, which may limit abuse 
potential.
104,108 A double-blind randomized crossover study to test abuse liability found that lorcaserin 
was similar to placebo with respect to subjective liking, overall liking, and ratings on desire to take the 
drug again.
108 Exceeding the recommended lorcaserin dose levels (10 mg, twice daily) were associated 
with higher levels of known unpleasant side effects and subjective dislike, compared to placebo.
108 
Thus, lorcaserin dose escalation would result in primarily negative subjective effects; these self-
regulating properties will likely limit the medication’s abuse liability.
70,10 
 
 
3. STUDY OBJECTIVES 
3.1 Primary Objective 
The primary objective is to evaluate the feasibility, tolerability, acceptability and adherence of lorcaserin 
versus placebo (2:1) to reduce cocaine use disorder among 45 MSM cocaine users over 12 week treatment 
period.  
3.2 Secondary Objectives 
To evaluate the preliminary efficacy of lorcaserin versus placebo to reduce cocaine use and 
HIV-related sexual risk behaviors among MSM with cocaine use disorders, as determined by the 
proportion of cocaine-positivity from twice weekly urine samples and self-reported sexual behaviors over a 
12 week treatment period. 
 
4. STUDY DESIGN 
4.1 Study Overview 
The goal of the  TLC Study is to evaluate the feasibility, tolerability, acceptability and adherence for 
lorcaserin among actively using, MSM with cocaine use disorders in a placebo-controlled 12-week trial. In 
a double-blind trial, 45 individuals will be randomly assigned (2:1) to receive 12 weeks of lorcaserin 20mg 
(n=30) or placebo (n=15), to be taken once a day. 
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: 
• 
Experimental treatment:  BELVIQ® XR (lorcaserin). 20 mg.   
• 
Placebo or Comparator – Placebo, 20 mg.   

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Total duration of subject participation will be twelve weeks.  Total duration of the study is expected to be 
16 weeks. 
5. CRITERIA FOR EVALUATION 
5.1 Primary Efficacy Endpoint 
For the primary efficacy endpoint, we conservatively estimate that the sample will provide 80% power to 
detect reductions of 29 percentage points in the rate of cocaine urine positivity.  The time course for which 
this endpoint will be assessed will be from baseline to 12 week end of treatment.   We will also evaluate 
between-group differences on changes in: 1) any cocaine positive samples, defined as having a positive 
urine or sweat patch sample, over follow-up; 2) any cocaine positive samples or self-report of cocaine use in 
text messages; and 3) cocaine positivity from sweat samples only. 
 
5.2 Secondary Efficacy Endpoints 
For the secondary efficacy endpoint, to evaluate treatment effects on cocaine-associated sexual risk 
behaviors, GEE Poisson, binomial, and negative binomial models will be used to assess treatment effects 
on HIV sexual risk behaviors including high-risk sexual behaviors while under the influence of cocaine.  
5.3 Safety Evaluation: 
• 
Change in clinical laboratory findings  
• 
Incidence of adverse events 
6. SUBJECT SELECTION 
6.1 Study Population 
Men who have sex with men with a diagnosis of cocaine use disorder who meet the inclusion and 
exclusion criteria will be eligible for participation in this study.   
 
6.2 Inclusion Criteria 
1) Male gender;  
2) self-reported anal intercourse with men in the prior six months while under the influence of cocaine;  
3) cocaine use disorder by DSM-V SCID criteria;  
4) current cocaine use confirmed by urinalysis and cocaine use at least 1 day in the past 30 days;  
5) HIV-negative by rapid test or HIV-positive with medical record of HIV infection;  
6) no current acute illnesses requiring prolonged medical care;  
7) no chronic illnesses that are likely to progress clinically during trial;  
8) able and willing to provide informed consent and adhere to visit schedule; 
9) age 18–65 years;  
10) Baseline CBC, total protein, albumin, glucose, alkaline phosphatase, creatinine, BUN, and 
electrolytes without clinically significant abnormalities as determined by study clinician in 
conjunction with symptoms, physical exam, and medical history.  
11) Written informed consent (and assent when applicable) obtained from subject or subject’s legal 
representative and ability for subject to comply with the requirements of the study. 

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6.3 Exclusion Criteria 
1) Any psychiatric condition (e.g., depression with suicidal ideation, schizophrenia) or medical condition 
that would preclude safe study participation;  
2) HIV-positive test result at screening visit but previously unaware of HIV infection (i.e., newly 
diagnosed with HIV infection at screening; those with a medical record of HIV infection are eligible);  
3) any moderate to severe alcohol or substance use disorders (other than cocaine use disorders), according 
to DSM-V criteria;  
4) known allergy or previous adverse reaction to lorcaserin;  
5) current CD4 count < 200 cells/mm3 ; 
6) severe liver impairment (Child-Pugh score > 9);  
7) severely impaired renal function (creatinine clearance £ 30 ml/min);  
8) use of medications that affect the serotonergic neurotransmitter system (e.g., selective serotonin 
reuptake inhibitors (SSRIs), selective serotonin- norepinephrine reuptake inhibitors (SNRIs), 
tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs));  
9) predisposition to priapism;  
10) currently participating in another longitudinal intervention research study;  
11) body mass index (BMI) ≥ 30 with desire to use weight management medication, or BMI > 40; 
12) BMI < 15; 13) anticipated use of agents that are associated with valvulopathy and/or pulmonary 
hypertension 
7. 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. 
7.1 Allowed Medications and Treatments 
Standard therapy is allowed except for treatments noted in the exclusion criteria described above and as 
noted in the prohibited medications section below.   
 
7.2 Prohibited  Medication and Treatments 
No prohibited medication or treatment besides those in the exclusion criteria. 
 
8. STUDY TREATMENTS 
8.1 Method of Assigning Subjects to Treatment Groups 
Up to 45 eligible participants will be randomly assigned to lorcaserin or placebo treatment groups in a 2:1 
allocation ratio (lorcaserin and placebo), using the computer-generated randomization code for the study 
blocks. Assignment of two-thirds of participants to the lorcaserin arm was specifically chosen to improve 
our ability to detect adverse events in the active treatment arm, while preserving our ability to assess 
recruitment in a study in which randomization to placebo is likely. The study biostatistician, Dr. 

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Vittinghoff, will generate and provide the randomization code directly to the pharmacy. No study staff 
will have access to the code. 
8.2 Blinding 
Due to the objectives of the study, the identity of test and control treatments will not be known to 
investigators, research staff, or participant.  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 test and control treatments will be identical to maintain the blind.  
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. When possible, the Investigator should 
discuss the emergency with the Medical Director prior to unblinding.   
8.3 Formulation of Test and Control Products 
Drug Name and Active Ingredients 
 
Name(s): BELVIQ® XR 
Active Ingredients: lorcaserin hydrochloride 
Pharmacological Class 
BELVIQ®  XR (lorcaserin hydrochloride) is a serotonin 2C receptor agonist for oral administration 
used for chronic weight management. [1] 
Structural and Chemical Formula 
Its chemical name is (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride 
hemihydrate. The empirical formula is C H Cl N·0.5H O, and the molecular weight of the hemihydrate 
form is 241.16 g/mol.[1] 
The structural formula is: 
 
 
Formulation of Dosage 
This drug is in the form of an orange, film-coated, round, film-coated, 20 mg extended release tablet. 
The tablets are biconvex, debossed with “A” on one side and “20” on the other side 
For this investigation, BELVIQ® XR will not be compounded. We will have Safeway Pharmacy 
(located at 6100 Hellyer Avenue, Suite 100 San Jose, CA 95138) encapsulate the BELVIQ® XR pill in 
whole form and create identical placebo capsules.[1] 
Route of Administration 

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Packaging and Labeling 
Safeway Compounding Pharmacy, 6100 Hellyer Ave Ste 100, San Jose, CA, 95138, is used to provide 
study drug. Each treatment bottle from the UCSF pharmacy was labeled with the study drug number, 
prescribing physician name (medical director), required FDA warning statement, emergency pager 
number, directions for participant use and storage, and expiration information. Each treatment bottle from 
Safeway pharmacy is labeled with the study drug number, principal investigator name, prescribing 
physician name (medical director), required FDA warning statement, emergency pager number, directions 
for participant use and storage, and lot and expiration information. 
 
Sample Label: 
 
8.4   Supply of Study Drug at the Site 
The Safeway Compounding Pharmacy (San Jose, CA), which is currently supplying the study drug for our 
ongoing trials, will prepare and supply lorcaserin and placebo in identical-looking gel capsules to maintain 
blinding. The initial study drug shipment will be shipped after site activation (i.e., all required regulatory 
documentation has been completed). Subsequent study drug shipments will be made after site request for 
resupply. 
8.4.1Dosage/Dosage Regimen 
The recommended dose of BELVIQ® XR is one 20mg tablet administered orally once daily.[1] 
8.4.2 Dispensing 
Study medications will be dispensed by the study clinician (licensed medical practitioner) in treatment 
bottles that are labeled with the study drug number, principal investigator name, prescribing physician 
name (medical director), required FDA warning statement, emergency pager number, directions for 
participant use and storage, and lot and expiration information. 
 
Further, at time of study drug dispensing, the study clinician will review with the participant how to take 
the study medication, possible side effects they may encounter, and how to access the study clinician by 
emergency pager if necessary. The study clinician will also answer any questions the participant might 
have. 
8.4.3 Administration Instructions  
Participants will receive training on dosing at enrollment. Participants will be given a week’s supply of 
20mg tablets at enrollment and at weekly visits; they will be instructed to only take 1 tablet every 24 
hours. This optimal dose was informed by pharmacokinetic studies which estimated that 20mg of 
lorcaserin has a mean plasma half-life of 11 hours and once daily 20mg dosing of lorcaserin will lead to 
steady state within 3 days of treatment.
104  

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8.4.4 Storage 
Study drug should be stored by the study site at controlled room temperature, 15 to 30ºC (59 to 86ºF). If 
the temperature of study drug storage in the clinic/pharmacy exceeds or falls below this range, this should 
be reported to the Principal Investigator and captured as a deviation. Subjects will be instructed to store 
the medication in original packaging at room temperature according to the instructions outlined on the 
Drug Administration Instructions. 
8.5 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.   
8.6 Measures of Treatment Compliance 
Study medications will be dispensed by the study clinician in MEMs cap dispensers with dosing 
instructions, date of dispensing, prescribing clinician, a 24-hour telephone study phone number for 
medical emergencies, and advisements against drug combinations. MEMS Caps will track adherence 
daily; each dispenser opening is recorded as a medication event sent to a remote database in real time 
9. 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 or 
subject’s legal representative.  If appropriate, assent must also be obtained prior to conducting any study-
related activities. 
9.1 Clinical Assessments 
Concomitant Medications 
All concomitant medication and concurrent therapies will be documented at Baseline/Screening and at 
Month 1, Month 2 and Month 3 visits.  Dose, route, unit frequency of administration, and indication for 
administration and dates of medication will be captured. 
Demographics  
Demographic information (date of birth, gender, race) will be recorded at Screening. 
Balloon Analogue Risk Tast (BART)  
To better understand the mechanism in which lorcaserin may reduce cocaine and cocaine-
associated sexual risk behaviors, we will evaluate lorcaserin’s effect on impulsivity through two 
validated measures of impulsivity: the state impulsivity scale (the STIMP)183 and the Balloon 
Analogue Risk Task (BART).182 We will evaluate changes in cocaine craving by arm using the 
visual analog scale for craving187 and the Minnesota cocaine craving scale.188 
Medical History  
Relevant medical history, including history of current disease, other pertinent respiratory history, and 
information regarding underlying diseases will be recorded at Screening. 

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Physical Examination 
A complete physical examination will be performed by the study clinician at Screening, 
Enrollment, Month 1, Month 2, and Month 3 visits.   Qualified staff (MD, NP, RN, and 
PA) may complete the abbreviated physical exam at all other visits.  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 Enrollment, Month 1, Month 2 and Month 3 visits 
Electrocardiogram (ECG):  
The ECG will be administered during screening to assist in determination of participant 
eligibility and again at study exit (ie. week 12/Month 3) to assess safety at termination. 
The ECG tracings will be reviewed by a qualified medical clinician for accuracy at the 
site. 
 
Urinalysis for Cocaine Use 
Urinalysis for Cocaine Use: Urine samples will be collected once a week and tested for cocaine metabolites 
(benzoylecgonine) with EZ-SCREEN screening assays (MedTox Diagnostics, Inc., Burlington, NC). On 
average, cocaine is detectable in urine for approximately 72 hours. To detect use over weekends, when 
cocaine use is likely to be higher compared to the remainder of the week.  Furthermore, the MedTox 
assays we will use for urine toxicology tests can also detect the following classes of substances: 
amphetamine, barbiturates, benzodiazepines, buprenorphine, methadone, methamphetamine, opiates, 
oxycodone, phencyclidine, propoxyphene and THC (cannabinoids).   
 
Sweat Testing Using Perspiration Patches 
To further enhance our ability to detect cocaine use, we will also utilize tamper evident sweat 
patches—PharmChek Drugs of Abuse Sweat Patch (PharmChem, Inc., Fort Worth, Texas)—that absorb 
perspiration 24 hours per day, for up to 10 days of continuous wear.
8 These patches will be tested for the 
presence of cocaine and cocaine metabolites, using testing procedures approved by the FDA since 1995.
8 
Pharmchek patch enzyme immunoassays to detect cocaine in sweat have been found to have 94-95% 
sensitivity and 91-99% specificity rates, compared to gas chromatography-mass spectrometry.
166,167 At 
baseline visit, we will affix patches on all participants (see Figure 6). These patches have a semi-
permeable membrane to allow oxygen, carbon dioxide and water vapor to pass through the patch, 
keeping the skin underneath sterile and healthy. At each weekly follow-up visit, we will replace the 
used patch worn since the prior visit and send those used patches for  
cocaine testing to PharmChem’s laboratories. These patches will retain cocaine and cocaine 
metabolites for any use during the period it was worn. Hence, we anticipate no gaps in the window of 
detection for cocaine use. Extra replacement patches will be provided to participants at weekly visits, 
in anticipation of the rare event that a patch falls off prematurely; participants will be instructed to use a 
replacement patch when needed. Used patches will be collected and tested weekly. In sensitivity 
analyses, we will impute cocaine-positive results for weeks in which multiple patches were used or 
when patches fell off. 
 
HIV Testing and Counseling: 

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Participants will receive standard HIV risk reduction counseling
168 at screening and at month 3 visits with 
HIV rapid test and pooled viral load (HIV-negative participants) or CD4 and viral load testing (HIV-
positive participants). Participants with positive rapid tests will have a confirmatory Western Blot assay 
performed and will receive HIV counseling and referrals to HIV service providers. Participants newly 
diagnosed with HIV at screen will be referred to community resources. Consistent with our prior trials, 
after obtaining the participant’s permission, we will contact LINCS (Linkage, Integration, Navigation, and 
Comprehensive Services), a program of the San Francisco Department of Public Health (SFDPH), which 
provides coordinated comprehensive linkage to care, navigation and partner services for HIV-positive 
people living in San Francisco, particularly those who are newly HIV-positive and those who have fallen 
out of care. 
Substance Use Counseling 
 In addition to HIV risk-reduction counseling done at screening and month 3 visits, all participants will 
receive weekly 30-minute substance use counseling. This standardized protocol is based on a manual-
driven psychosocial treatment program using cognitive behavioral therapy,
169 motivational 
interviewing techniques,
170,171 and incorporating the Stages of Change Model.
172 This platform has been 
used to treat substance use and has high acceptability among substance-using MSM.
122,173-175 
Counseling will be provided by trained study staff closely supervised by a licensed clinical psychologist 
in weekly quality assurance session. 
Ecological Momentary Assessments (EMA) Messages:  
As with our Project iN and Better THAN pharmacologic trials, participants will receive daily EMA 
texts to collect data on cocaine use patterns and medication compliance (see sample texts shown 
Figure 5).
163 Messages will use shorthand notations to maintain participant confidentiality. Participants 
will be trained on text messaging procedures and receive a reference guide during enrollment (sample 
guide from The Project iN Study included in the Appendix). Participants will be encouraged to regularly 
delete text messages and encrypt their phone with passwords for privacy. Our current studies already 
utilize this technology with great success and the majority of our participants prefer text appointment 
reminders. Moreover, text messaging has been highly acceptable in health and research settings.110 
 
Medical Safety and AE Assessments:  
Blood specimens will be collected via venipuncture using universal precautions. Medications taken in 
the 30 days prior to enrollment and while enrolled in the study will be documented. Because lorcaserin 
is not approved for cocaine use, we include extensive safety parameters, as is required by the Food and 
Drug Administration when testing a medication for a new indication. AEs and concomitant 
medications will be elicited from participants verbally and documented weekly. As previously noted, 
participants will also be given the 24-hour study phone number to communicate with the study 
clinician in the event of an emergency. Clinicians will follow the “Division of AIDS Table for Grading 
the Severity of Adult and Pediatric Adverse Events” (version 2.0) and UCSF IRB reporting 
guidelines.179 Safety monitoring will include assessment, follow-up, and reporting of clinical and 
serious AEs, and abnormal lab results. 
Addressing Medical/Social Needs:  
While our study will not provide direct medical care, we may identify problems and will provide 
referrals, identifying community providers suited for individual participants (sample list of resources 
referrals). Clinical staff will be available as needed for clinical consultation. 

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Qualitative Interviews:  
All participants will be scheduled for in-depth semi-structured interviews at their 12-week treatment visit. 
Qualitative experts, Drs. Wilson and Matheson will conduct interviews to explore participant treatment 
and study acceptability and assess medication adherence challenges. Semi-structured interview guides 
will begin with a discussion of motivations for treatment seeking and ask about the participant’s history of 
drug use and treatment programs. The guide will then assess overall experiences as part of the study (e.g., 
frequency of study visits, frequency of medication dosing, appraisal of study activities and staff, study 
location). Participants who have experience with pharmacologic interventions for substance use treatment  
will be asked to compare their experiences 
Adverse Events 
Information regarding occurrence of adverse events will be captured throughout the study. 
Duration (start and stop dates and times), severity/grade, outcome, treatment and relation to 
study drug will be recorded on the case report form (CRF). 
9.2 Clinical Laboratory Measurements  
Hematology 
Blood will be obtained and sent to each site’s clinical hematology lab for 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, gamma-glutamyl transferase (GGT), 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 cocaine 
metabolites (benzoylecgonine). On average, cocaine is detectable in urine for approximately 72 hours.  
 
10. EVALUATIONS BY VISIT 
10.1 VISIT 1 (SCREENING VISIT—WEEK 1 ) 
Review the study with the subject (subject’s legal representative) and obtain written informed consent and 
HIPAA authorization and assent, if appropriate. 
Assign the subject a unique screening number. 
Record demographics data. 

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Record medical history, including a history of mental health, sexual behaviors and substance use, 
diagnosis date, and prior cocaine treatments. 
Record concomitant medications. 
Perform a complete physical examination. 
Collect urine sample for cocaine use and other substances test.  If capable of becoming pregnant then a 
pregnancy test.  Record results. 
If urine is not positive for cocaine metabolites then place a sweat patch on participant. 
10.2 Visit 2 (Screening Visit – week 2) 
Perform and record vital signs (including weight and height for calculating BMI)  
Perform and record results of blood pressure testing. 
Perform and record results of ECG 
Collect blood for clinical laboratory tests (chemistry, hematology, HIV test, pooled viral load test.  If HIV 
positive, a CD4 test). 
Collect and record contact information 
Collect urine sample for cocaine use and other substances test.  If capable of becoming pregnant then a 
pregnancy test.  Record results. 
If urine is not positive for cocaine metabolites then place a sweat patch on participant. 
 
10.3 Visit 3 (Enrollment Visit – month 1) 
 Assign randomization.  You are assigned by a computer by chance to either the lorcaserin hydrochloride 
or placebo groups.  
Collect urine to test for cocaine metabolites and other substances.     
If capable of becoming pregnant, we will collect urine and perform a pregnancy test. 
Perform and record results for the BART test. 
Provide study medication (lorcaserin or placebo) in medical monitoring devices (“MEMS” containers). 
MEMS devices will record each time you open the container to retrieve a study medication capsule.   
Provided with a Wallet Card that explains that you may or may not be on a study medication (lorcaserin 
or placebo). This card will provide the study clinician’s pager number who can provide information to 
other doctors in the event of an emergency.  The card will also instruct the emergency room or other 
doctor providing treatment to provide information to the study clinician about the care they provide. 
Perform ACASI questionnaire on a computer.   
Meet with counselor about cocaine use. 
Initiate Ecological Momentary Assessments 
10.4 Visit 4 (weeks 1, 2, 3, 5, 6, 7, 9, 10, and 11)) 
Record any Adverse Experiences and dosing compliance by downloading MEMs cap dispenser. 
Meet with the counselor regarding cocaine use and use of the study medication. 
Collect urine sample to test for cocaine use and other substances.  If capable of becoming pregnant, we 
will also conduct a pregnancy test. 
Answer ACASI questions on a compute 

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Receive the study medication: if needed, you will be given more of the study medication (except at the 
week 12 visit). 
Meet with the study doctor or nurse: to talk about any problems with the study medication or any changes 
in your health or medications if needed. A physical exam may be done.  
 
10.5 Visit 5 (Month 1, 2 and 3 with visit window 2 weeks before visit and 2 weeks after visit) 
All the same procedures as the weekly visits PLUS these additional procedures:  
Answer ACASI questions on a computer about your mood, your recent sexual behavior and drug use, and 
your feelings about being in the study.  
Record any Adverse Experiences and dosing compliance. 
Record changes to concomitant medications. 
Perform and record results for the BART test.  
Meet with the study doctor or nurse: to talk about any problems with the study medication or any changes 
in your health or medications if needed. A physical exam may be done. 
Collect blood for clinical laboratory tests (chemistry, hematology).   
 
At month 3 visit, collect blood for HIV test, pooled viral load test.  If HIV positive, a CD4 test. 
At month 3 visit, perform and record ECG results. 
At month 3, perform qualitative exit interview.  
10.6 Early Withdrawal Visit 
Record any Adverse Experiences and/or Review for adverse experiences and exclusionary medication 
use. 
Record changes to concomitant medications. 
Perform complete physical examination. 
Perform and record vital signs. 
Collect blood for clinical laboratory tests:  Chemistry, Hematology, Urinalysis, Pregnancy (urine or 
serum). 
 
11. ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION 
11.1 
Adverse Events 
An adverse event (AE) is any untoward medical occurrence in a clinical investigation of a patient 
administered a pharmaceutical product and that does not necessarily have a causal relationship 
with the treatment.  An AE is therefore any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom or disease temporally associated with the administration 
of an investigational product, whether or not related to that investigational product.  An 
unexpected AE is one of a type not identified in nature, severity, or frequency in the current 
Investigator’s Brochure or of greater severity or frequency than expected based on the 
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The Investigator will probe, via discussion with the subject, for the occurrence of AEs during 
each subject visit and record the information in the site’s source documents.  Adverse events will 
be recorded in the patient CRF.  Adverse events will be described by duration (start and stop 
dates and times), severity, outcome, treatment and relation to study drug, or if unrelated, the 
cause. 
11.2 AE Severity 
The National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) 
Version 3.0 should be used to assess and grade AE severity, including laboratory abnormalities 
judged to be clinically significant. The modified criteria can be found in the study manual.  If the 
experience is not covered in the modified criteria, the guidelines shown in Table 1 below should 
be used to grade severity.  It should be pointed out that the term “severe” is a measure of 
intensity and that a severe AE is not necessarily serious. 
Table 1.  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 should be assessed using the following the guidelines 
in Table 2. 
Table 2.  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 
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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. 
11.3 
Serious Adverse Experiences (SAE) 
An SAE is defined as any AE occurring at any dose that results in any of the following 
outcomes: 
• 
death 
• 
a life-threatening adverse experience 
• 
inpatient 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.  
 
11.3  Medical Monitoring 
John Walker, RN, FNP-C, research clinician, should be contacted directly at these numbers to report 
medical concerns or questions regarding safety. 
 
 
 
 
Phone:  (628) 217-6227 
 
 
 
Pager:  (415) 356-8980 
 
Phillip Coffin, MD MIA FACP FIDSA, medical director, should be contacted directly at this number to 
report medical concerns or questions regarding safety. 
Phone: (510) 407-2603  
   
12. DISCONTINUATION AND REPLACEMENT OF SUBJECTS 
12.1 Early Discontinuation of Study Drug  
A subject may be discontinued from study treatment at any time if the subject or the investigator 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 

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• 
Protocol violation requiring discontinuation of study treatment 
• 
Lost to follow-up 
• 
PI or clinician request for early termination of study 
• 
Positive pregnancy test (females) 
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. 
12.2 Withdrawal of Subjects from the Study 
A subject may be withdrawn from the study at any time if the subject or the investigator 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.  
As noted above, subjects who discontinue study treatment early (i.e., they withdraw prior to Week 8 Visit 
) should have an early discontinuation visit. Refer to Section 10 for early termination procedures.  
Subjects who withdraw after Week 8 Visit  but prior to Week 12 Visit  should be encouraged to come in 
for a final visit (and the procedures to be followed would include those for their next scheduled visit).   
12.3 Replacement of Subjects 
Subjects who withdraw from the study treatment will not be replaced.   
13. PROTOCOL VIOLATIONS 
A protocol violation occurs when the subject or 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 (such as those listed in the exclusion criteria) 
 
Failure to comply with Good Clinical Practice (GCP) guidelines will also result in a protocol violation. 
The PI 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. This form will be signed by a Sponsor representative and the 
Investigator. A copy of the form will be filed in the site’s regulatory binder and in the Sponsor’s files. 

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14. DATA SAFETY MONITORING  
The PI along with the site physician Dr. Coffin, will be responsible for ensuring proper monitoring of the 
safety and efficacy of this trial, including the execution of the DSM plan, and complying with the 
reporting requirements, including reports to the IRB, DSMB, NIDA and (where applicable) the FDA (see 
Figure 1 below). 
 
The 
research 
team 
including 
the PI, 
clinicians, 
data 
manager, 
research 
associates
, and 
recruitme
nt 
coordinat
or, meets weekly to discuss all aspects of the study such as recruitment and retention, clinical or 
counseling issues, and any regulatory or operation issues.  All study documents are monitored by the 
study coordinator for quality assurance on a weekly basis to ensure timely corrections to charting such as 
missing initials or cross-outs with error-correction.  Although there is no outside monitor, the clinicians 
review each other’s charts for accuracy, consistency, and adherence to protocol. Regular audits will be 
conducted as well on consent forms, laboratory logs and other data collection forms. 
 The interim DSMB report will contain a brief description of the trial, baseline socio‐demographic 
characteristics of participants, retention and disposition of study participants, a description of any quality 
assurance or regulatory issues, a report of AEs and SAES, and the status of outcome data.  
 Members and affiliation:  We will use the existing University of California, Los Angeles (UCLA) Data & 
Safety Monitoring Board for Addiction Medicine (DSMBAM), which has extensive experience in 
monitoring pharmacologic interventions, including among vulnerable populations. The DSMBAM has 
monitored all of our pharmacologic trials for substance users.    
 To ensure that the DSMB oversight of the study remains independent from the proposed study, the 
PI(Santos) as well as others who serve on the DSMBAM that might be linked with the study in some way 
recuse themselves from review of the present study.  
 The purpose of the DSMBAM is to provide oversight and monitoring of Phase I and Phase II clinical 
trials of pharmacological and behavioral treatments for stimulant dependence. There are three 
fundamental charges of the board, which are:  
• 
To ensure the safety of trial participants   
• 
To preserve validity and integrity of research data   
• 
To facilitate the availability of timely as well as reliable findings to the broader clinical 
community   
Below are members who serve as committee chairs as well as clinical research experts:  
 
PI (Santos) and 
Medical 
Director 
(Coffin) 
oversight: 
reports to IRB, 
NIDA, and FDA 
as required 
Subjects enroll and complete study visits 
Medical staff members evaluate subjects during 
trial 
Figure 1: 
Initial protocol review: NIDA, IRB; 
approve data safety monitoring process 
for the trial
DSMB: Two 
members review 
medical progress; 
statistician reviews 
symptom 
complaints; reports 
to PI (Santos), IRB, 
NIDA, FDA as 
required 
 

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• Steven Shoptaw, PhD, is Professor in both the Department of Family Medicine and the Department of 
Psychiatry and Biobehavioral Sciences at UCLA. Over the past 20 years, Dr. Shoptaw has conducted a 
series of clinical studies in community clinic settings, primarily on topics that involve developing medical 
and behavioral interventions to treat substance abusers.  
• Timothy M. Hall, MD, PhD, is Health Sciences Assistant Clinical Professor at UCLA Department of 
Family Medicine and Center for Behavioral and Addiction Medicine. His research expertise is in sexual 
identity formation, social/sexual MSM networks, non-gay-identified MSM, ethnography and MSM 
substance use.  
• Gayle Baldwin, PhD, is Associate Professor in the Department of Medicine at the University of 
California, Los Angeles. Her research focuses on how specific immune cells fight infectious diseases and 
cancer.  
• Dominick Frosch, PhD, is an Associate Staff Scientist in the Department of Health Services Research at 
the Palo Alto Medical Foundation’s Research Institute. He is also an Assistant Professor of Medicine at 
the University of California, Los Angeles. His research is focused on developing and implementing 
interventions to increase patient participation in clinical decision making and understanding the effects of 
health information in the media on behavior.  
 
Below are members who serve as experts in biostatistics and epidemiology:  
• Scott Comulada, PhD  
• Sung-Jae Lee, PhD  
• Jesse Fletcher, PhD  
 
Below are members who serve as clinical research experts:  
• Adam Carrico, PhD  
• David Farabee, PhD  
• Timothy Fong, MD  
• Liz Evans, PhD  
• Lara Ray, PhD  
 
Administrative support staff:  
• Uyen Kao, MPH, Director  
• Oluwadamilola O. Jolayemi, MSc, Coordinator  
 
The DSMC evaluates known risks to subjects’ participation, the safety of the subjects as pre-specified in 
the protocol, and monitors the operational performance of the trial. The DSMC makes recommendations 
to continue, amend, or terminate the trial based on their findings. Recommendations are made in writing 
to the study investigators. The DSMC are given blinded trial data, but may request unblinding if safety 
data warrant. The initial review includes a review of the following items: statement of the protocol design, 
characteristics of the study data collection site, inclusion/exclusion criteria, randomization plan, definition 
of participants (e.g., screened, enrolled, randomized, treated, drop-out, lost to follow-up), intervention 
definition, dosage and frequency of study drug, reasons to discontinue study or to terminate individual 

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participants, reasons to discontinue treatment, outcome measures, sample size target, key adherence and 
safety variables, and the data analysis plan.  
Subsequent ongoing reviews include: enrollment data, including those screened, enrolled, and active; 
subject eligibility; demographic characteristics of participants (total, and by group), recruitment and 
retention (total and by group). Protocol compliance are evaluated by reviewing: the expected recruitment 
rate, study drop-outs and reasons for leaving the study, data quality assurance reports, overall data flow 
procedures, CRFs collected, received, and entered; protocol deviations; protocol violations; missing data; 
staff omissions; subject refusal to provide data; adherence to stopping rules. The data safety report are 
provided in total and by group, and include any relevant medical, psychosocial or laboratory data, AEs 
summarized in tables, individual SAE reports, concomitant medications, and concomitant illnesses. The 
outcome data report includes outcome data analyzed by group, masked or unblended, with or without 
statistical analyses, and include all outcome variables. 
15. STATISTICAL METHODS AND CONSIDERATIONS 
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.   
15.1 Data Sets Analyzed 
All eligible patients who are randomized into the study and receive at least one dose of the study drug (the 
Safety Population) will be included in the safety analysis. 
15.2 Demographic and Baseline Characteristics 
The following demographic variables at screening will be summarized by treatment group: race, gender, 
age, educational attainment, employed, and HIV positivity. 
15.3 Analysis of Primary Endpoint 
To establish the feasibility of enrolling and retaining 45 MSM with cocaine use disorder in a 12 week 
with 2:1 randomized, double-blind study of lorcaserin versus placebo. We will calculate the following 
feasibility measures: 1) proportion of those eligible among those screened; 2) proportion enrolled 
among those eligible; and 3) study completion rate. Process measures (e.g., visit length, counseling 
session completion) and reactions to study procedures will also be collected and reported. Between-
group differences will be assessed using Fisher’s exact and Wilcoxon rank sum tests. We will also 
calculate Kaplan-Meier curves for time to dropout, by group, and test for differences using the log-rank 
test. Precision: In the overall sample of 45, proportions will be estimated with margins of sampling 
error (MSEs; i.e., half widths of 95% confidence intervals) of ≤14.4 percentage points, and means with 
MSEs of 0.30 standard deviations, both typical for a small pilot study. While the study will only be 
powered to detect large between-group differences in process measures, it will provide warning of 
potential problems. 
 To explore the tolerability of lorcaserin versus placebo among MSM with cocaine use disorders, as 
determined by the number of adverse clinical events in the cocaine and placebo arms. We will compute 
the proportions of those experiencing adverse events, both overall and by type. Adverse clinical events, 
AEs and SAEs, and other binary safety outcomes will be presented as percent of participants that 
experience the safety outcome by treatment assignment. We will also classify AEs as any AE that results 
in stopping study medication, specific common AEs (>2% in both groups), AEs for general organ 
system categories, and AEs potentially related to study drug. The probability of observing at least one 
AE with population incidence of 1, 2, and 5% in the active arm will be 26, 45, and 70% with 2:1 
randomization, respectively. 

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To describe the acceptability and adherence for lorcaserin versus placebo MSM with cocaine use 
disorders. We will measure the acceptability of lorcaserin compared to placebo among participants 
through a qualitative interview and survey evaluations of the study procedures, study drug 
characteristics, and dosing schedule at the final visit. We will determine medication adherence via 
MEMs Cap data, pill count, and self-report from TLFB and SMS texts. Measures of interest will 
include percent of doses taken, patterns of adherence, and time to stopping medication. We will assess 
how these measures of adherence track with patterns of cocaine use as measured in TLFB and 
urinalysis. Concordance of the adherence measures will be examined using weighted Kappa and 
correlations. Qualitative Analysis: In-depth, semi-structured qualitative interviews will be analyzed 
to establish the acceptability of study procedures and study medication, and identify key factors 
affecting treatment adherence for MSM with cocaine use disorders. Transcribed semi-structured 
interviews will be imported into Atlas.ti, a qualitative research software program. Data will be separated 
by study arm initially to determine if adherence differed between groups. If it appears there were no 
differences between placebo and study drug arms, then we will collapse data to assess study 
acceptability and adherence challenges together. If there are noticeable differences, we will analyze 
each set of data separately. In either scenario, we will utilize two qualitative analytic methods to 
interpret data.190 First, content analysis to assess a priori themes using a structured codebook will 
allow us to focus on answering study questions about acceptability of study procedures and medication 
adherence. Second, thematic analysis primarily focused on adherence challenges will be 
conducted using open coding to allow themes to emerge from the data.191 A coding system for the 
thematic analysis will be developed using an iterative process. In the initial phase, Drs. Wilson and 
Matheson will review transcripts and field notes to become familiar with the data, and the analytic 
team will make notes of their observations and potential codes for use in the initial analysis meeting. 
Then a thematic codebook consisting of the code definition and inclusion and exclusion criteria will be 
created to aid analysis. In addition to anticipated adherence challenges, additional codes will be 
developed independently by each analytic team member through an inductive process of identifying 
themes that emerge from the data. Group analysis meetings will be held to compare independently 
developed codes for similarity and further definition. A consensus will be reached regarding each 
code, its application, and definition. To ensure consistency, a codebook and dictionary will be 
developed with universal definitions for each code. Inter-rater reliability: The two coders will assess 
inter-rater reliability by calculating the correlation between a set of ratings done by two independent 
raters for the initial set of 3–6 transcripts, and then again on the next set of 6 transcripts. After each 
inter-rater reliability assessment, the codebook and codes will be revised based on reconciliation of 
findings done between coders. Inter-rater reliability will be assessed as a team twice during the 
analysis process and again at the end of analysis as a post-hoc evaluation of reliability and validity. 
This evolving analysis process will ensure high quality of research decisions, the rationale behind 
decisions, and the responsiveness of investigators to the data.192 Once the thematic analysis 
codebook is developed and verified all remaining transcripts will be coded by study staff under the 
direction of Dr. Wilson. Further meetings will be held to discuss any differences in coding and to 
ensure consistency in the application of codes. Final analysis will begin with data reduction, then 
display, analysis and conclusion drawing using a conceptual framework in which hypothesized 
factors affecting adherence are assessed and unanticipated findings are identified.193 The analytic 
team will work from the coded data to merge findings into a final summary and a consensus of major 
themes, relationships between themes, and ranking of items of most importance to adherence. This 
method of data reduction encompassing both site- and team-based analysis creates a robust iterative 
process through which the data is thoroughly discussed and analytical consensus achieved. Atlas.ti 
software will be used to both code and develop data displays used in the analysis 

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15.4 Analysis of Secondary Endpoints 
To evaluate the preliminary efficacy of lorcaserin versus placebo to reduce cocaine use and HIV-
related sexual risk behaviors among MSM with cocaine use disorders, as determined by the proportion 
of cocaine-positivity from twice weekly urine samples and self-reported sexual behaviors. Minimum 
detectable effects (MDE) of the intervention on cocaine use outcomes will be substantial, as is 
typical of a pilot study. In our prior trial for MSM actively using stimulants, 68 the within-subject 
correlation of the repeated measures for urine positivity was 0.45, the urine positivity in the 
control group was 55%, and the retention was 93% at the end of the study. On this basis, we 
conservatively estimate that the sample will provide 80% power to detect reductions of 29 
percentage points in the rate of cocaine urine positivity. In preparation for a larger trial, we will 
conduct exploratory assessments using GEE Poisson models to assess treatment effects on 
cocaine urine positivity.194 In sensitivity analyses, we will also evaluate between-group 
differences on changes in: 1) any cocaine positive samples, defined as having a positive urine or 
sweat patch sample, over follow-up; 2) any cocaine positive samples or self-report of cocaine 
use in text messages; and 3) cocaine positivity from sweat samples only. Concordance of the 
urine testing, sweat testing, and self-reported measures will be examined using weighted 
Kappa and correlations. To evaluate treatment effects on cocaine-associated sexual risk 
behaviors, GEE Poisson, binomial, and negative binomial models will be used to assess 
treatment effects on HIV sexual risk behaviors including high-risk sexual behaviors while 
under the influence of cocaine. Findings from these analyses will be used to determine 
whether a linearly increasing or constant treatment effect best describes outcome 
patterns. 
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.   
15.5 Interim Analysis 
No planned interim analysis. 
15.6 Sample Size and Randomization 
 
16 DATA COLLECTION, RETENTION AND MONITORING 
16.1 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. Staff will upload data to the eCRF. Subjects will not be identified by name in the study 
database or on any study documents to be collected, but will be identified by subject number and 
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For eCRFs: If a correction is required for an eCRF, the time and date stamps track the person 
entering or updating eCRF data and creates an electronic audit trail.  For paper CRFs:  If a 
correction is made on a CRF, the study staff member will line through the incorrect data, write in 
the correct data and initial and date the change. 
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.  A copy of the CRF will remain at the Investigator’s site at the 
completion of the study. 
16.2 Data Management Procedures 
The data will be entered into a validated 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. 
16.3 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. For paper studies: 
Query reports (Data Clarification Requests) pertaining to data omissions and discrepancies will 
be forwarded to the Investigators and study monitors for resolution.  The study database will be 
updated in accordance with the resolved queries.  All changes to the study database will be 
documented. 
16.4 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.   
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. 
16.5 Availability and Retention of Investigational Records 
The Investigator must make study data accessible to the monitor, other authorized 
representatives of the Sponsor (or designee), 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 must 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.) must be kept secured for a period of two years following marketing of the 
investigational product or for two years after centers have been notified that the IND has been 
discontinued.  There may be other circumstances for which the Sponsor is required to maintain 

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study records and, therefore, the Sponsor should be contacted prior to removing study records for 
any reason. 
16.6 Monitoring 
Monitoring visits will be conducted by representatives of the Sponsor according to the U.S. CFR 
Title 21 Parts 50, 56, and 312 and ICH Guidelines for GCP (E6).    By signing this protocol, the 
Investigator grants permission to the Sponsor (or designee), and appropriate regulatory 
authorities to conduct on-site monitoring and/or auditing of all appropriate study documentation. 
16.7 Subject Confidentiality 
In order to maintain subject confidentiality, only a subject number and subject initials will 
identify all study subjects on CRFs and other documentation submitted to the Sponsor.  
Additional subject confidentiality issues (if applicable) are covered in the Clinical Study 
Agreement. 
17 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). 
17.1 Protocol Amendments 
Any amendment to the protocol will be written by the Principal 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. 
17.2 Institutional Review Boards 
The protocol and consent form will be reviewed and approved by the IRB of each participating 
center prior to study initiation.  Serious adverse experiences regardless of causality will be 
reported to the IRB/IEC in accordance with the standard operating procedures and policies of the 
IRB/IEC, and the Investigator will keep the IRB/IEC informed as to the progress of the study.  
The Investigator will obtain assurance of IRB/IEC compliance with regulations. 
Any documents that the IRB/IEC 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/IEC.  The IRB/IECs written unconditional approval of the study protocol 

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and the informed consent form will be in the possession of the Investigator before the study is 
initiated.  The IRB/IECs unconditional approval statement will be transmitted by the Investigator 
to prior to the shipment of study supplies to the site.  This approval must refer to the study by 
exact protocol title and number and should identify the documents reviewed and the date of 
review. 
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 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. 
17.3 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, assent and HIPAA authorization and provide the 
documents to the Sponsor or designee for approval prior to submission to the IRB/IEC.  The consent form 
generated by the Investigator must be acceptable to the Sponsor and be approved by the IRB.  The written 
consent document will embody the elements of informed consent as described in the International 
Conference on Harmonisation and will also comply with local regulations. The Investigator will send an 
IRB-approved copy of the Informed Consent Form to the Sponsor (or designee) for the study file. 
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 (or their 
legal representatives) must be given ample opportunity to inquire about details of the study.  If 
appropriate and required by the local IRB, assent from the subject will also be obtained.  If a subject is 
unable to sign the informed consent form (ICF) and the HIPAA authorization, a legal representative may 
sign for the subject.   A copy of the signed consent form (and assent) will be given to the subject or legal 
representative of the subject and the original will be maintained with the subject’s records. 
17.4 Publications  
The preparation and submittal for publication of manuscripts containing the study results shall be in 
accordance with a process determined by mutual written agreement among the Principal Investigator and 
participating institutions.  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.  
17.5 Investigator Responsibilities 
By signing the Agreement of Investigator form, the Investigator agrees to: 
1. 
Conduct the study in accordance with the protocol and only make changes after notifying the 
Sponsor (or designee), except when to protect the safety, rights or welfare of subjects. 

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2. 
Personally conduct or supervise the study (or investigation). 
3. 
Ensure that the requirements relating to obtaining informed consent and IRB review and approval 
meet federal guidelines, as stated in § 21 CFR, parts 50 and 56. 
4. 
Report to the Sponsor or designee any AEs that occur in the course of the study, in accordance with 
§21 CFR 312.64. 
5. 
Ensure that all associates, colleagues and employees assisting in the conduct of the study are 
informed about their obligations in meeting the above commitments. 
6. 
Maintain adequate and accurate records in accordance with §21 CFR 312.62 and to make those 
records available for inspection with the Sponsor (or designee). 
7. 
Ensure that an IRB that complies with the requirements of §21 CFR part 56 will be responsible for 
initial and continuing review and approval of the clinical study. 
8. 
Promptly report to the IRB and the Sponsor (or designee) all changes in the research activity and all 
unanticipated problems involving risks to subjects or others (to include amendments and IND safety 
reports). 
9. 
Seek IRB approval before any changes are made in the research study, except when necessary to 
eliminate hazards to the patients/subjects. 
10. Comply with all other requirements regarding the obligations of clinical investigators and all other 
pertinent requirements listed in § 21 CFR part 312. 
 

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Protocol Template © CFFT TDN   Effective: 12 SEP 2007 
18 APPENDICES 
Appendix 1:  Study Procedures 
 
Table 2. The TLC Study 
Procedures 
Scr 
1&2 Enr 
Wk 
Bi- 
wk 
Dly 
M 1&2 M 3 
Informed consent 
X 
Safety lab assessment 
X 
X 
X 
Rapid HIV test*, CD4, viral load 
X 
X 
HIV risk reduction counseling 
X 
X 
Medical history and SCID 
X 
Vital signs, weight 
X 
X 
X 
X 
Physical exam 
X 
X 
Medication Training 
X 
Randomization 
X 
Urine testing for cocaine 
X 
X 
X 
X 
X 
X 
Sweat patch testing for cocaine 
X 
X 
X 
X 
CAPI assessments 
X 
X 
X 
X 
AE assessments 
X 
X 
X 
Substance use counseling 
X 
Qualitative Interviews 
X 
Text Messaging 
X 
Notes: *Confirmatory HIV testing will be performed for reactive tests. Scr=Screening, 
Enr=Enrollment, Wk=Weekly, Bi-wk=Biweekly/twice weekly, Dly=Daily, M=Monthly 
 
18.2 Appendix 2:  References: 
 
1. 
Riezzo I, Fiore C, De Carlo D, et al. Side effects of cocaine abuse: multiorgan toxicity and 
pathological consequences. Curr Med Chem 2012;19:5624-46. 
2. 
Karila L, Petit A, Lowenstein W, Reynaud M. Diagnosis and consequences of cocaine 
addiction. Curr Med Chem 2012;19:5612-8. 
3. 
Substance Abuse and Mental Health Services Administration. Drug Abuse Warning 
Network, 2011: National Estimates of Drug-Related Emergency Department Visits Rockville, MD: 
HHS; 2013 04/14/2014. 
4. 
United Nations Office on Drugs and Crime. World Drug Report 2009. Vienna, 
Austria2009. 
5. 
Degenhardt L, Chiu WT, Sampson N, et al. Toward a global view of alcohol, tobacco, 
cannabis, and cocaine use: findings from the WHO World Mental Health Surveys. PLoS Med 
2008;5:e141. 
6. 
Anthony J, Warner L, Kessler R. Comparative epidemiology of dependence on tobacco, 
alcohol, controlled substances, and inhalants: Basic findings from the National Comorbidity 
Survey. Experimental and Clinical Psychopharmacology 1994;23:244. 
7. 
Degenhardt L, Baxter AJ, Lee YY, et al. The global epidemiology and burden of 
psychostimulant dependence: Findings from the Global Burden of Disease Study 2010. Drug 
Alcohol Depend 2014. 
8. 
Drugs of Abuse Sweat Patch. 2013. (Accessed 12/20/14, 2014, at 
http://www.pharmchem.com/default.asp?page=2.25.) 
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