STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy
Phase: PHASE1
Conditions: Methamphetamine-dependence, Methamphetamine Abuse
Sponsor: InterveXion Therapeutics, LLC

Study title: 
STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy 
Protocol number: 
M200C-1801 
NCT number: 
NCT03336866 
Document date: 
20Aug2019 
 

 
 
STAMPOUT:  
Study of Antibody for Methamphetamine  
Outpatient Therapy 
 
 
 
Protocol Identifying Number: M200C-1801 
Principal Investigators: Lynn Webster, MD and Peter Winkle, MD 
IND Sponsor: InterveXion Therapeutics, LLC 
IND Number: 110,179 
Version Number: 9 
20 Aug 2019 
 

ii 
 
SUMMARY OF CHANGES AND JUSTIFICATIONS 
 
Original protocol effective date: 08 September 2017 
 
Note: As applicable for current changes only, additions are indicated in underlined text and deletions are 
indicated in strikethrough text in the affected sections of the document. 
 
 
Item or Section(s) 
Justification 
Version 2 
Effective Date: 20 December 2017 
2.1 Background Information 
To note that nonclinical studies supporting this clinical protocol have 
been completed. 
2.2 Rationale; 
6.1.4 Preparation 
To limit the maximum dose of IXT-m200 given to 1500 mg as done in 
the Phase 1 protocol TOA62936. 
4.1.3 Exploratory Endpoints; 
5.2 Participant Exclusion Criteria; 
7.1.1 Study Specific Procedures; 
7.3.3 Inpatient Stay, Extension 
Stay, and Follow-up; 
7.3.6 Schedule of Events Table; 
8.1 Specification of Safety 
Parameters 
To delete reference to cardiac output measures and analysis. Cardiac 
output measurement is not feasible along with other measurements using 
currently accessible equipment and was to be used for an exploratory 
endpoint only. 
5.1 Participant Inclusion Criteria 
To clarify medically acceptable forms of birth control. 
5.2 Participant Exclusion Criteria; 
7.1.1 Study Specific Procedures; 
7.3.6 Schedule of Events Table 
To update and add normal ranges for vital signs; to annotate the 
collection of vital signs at -0.25 hr relative to the first METH dose; and 
to add a window of ±5 min for collection. 
6.1.2 Formulation, Appearance, 
Packaging, and Labeling 
To correct the methamphetamine vial size to 1 mL. 
7.1.1 Study Specific Procedures 
To allow for repeated ECG recordings; to add a window of ±10 min for 
collection; and to add that subjects will rest supine for 5 minutes prior to 
taking vital sign measurements. 
7.1.1 Study Specific Procedures; 
7.3.6 Schedule of Events Table 
To add criteria for appropriate subjective responses on Day 1 and remove 
DEQ assessment at 5 min after the METH doses. 
7.2.1 Clinical Laboratory 
Evaluations 
To update Serum Chemistry and Urinalysis tests and time points. 
7.2.2 Other Assays or Procedures 
To correct the sample size required for IXT-m200 serum PK and 
Immunogenicity analysis. 
7.3.1 Screening 
To note that either HIV antibody or nucleic acid tests may be done. 
7.3.3 Inpatient Stay, Extension 
Stay, and Follow-up 
To note priority order of tests to be done at the same time point. 
7.3.3 Inpatient Stay, Extension 
Stay, and Follow-up;  
7.3.6 Schedule of Events Table 
To note that C-SSRS assessments will be done on Day 22 for those 
discharging, or Day 29 for those participating in the inpatient extension 
stay. 
7.3.3 Inpatient Stay, Extension 
Stay, and Follow-up;  
7.3.4 Final Study Visit;  
7.3.6 Schedule of Events Table 
To reduce the number of SCID-DSM-V assessments during follow-ups. 
7.3.6 Schedule of Events Table 
To reduce the number of ECG recorded on METH challenge days. 
13.4 Participant and Data 
Confidentiality 
To update the source of the Certificate of Confidentiality to NIH and add 
award identification. 

iii 
 
 
 
Item or Section(s) 
Justification 
Version 3 
Effective Date: 09 March 2018 
Schematic of Study Design;  
6.1.8 Dose Adjustments/ 
Modifications/Delays;  
7.3.3 Inpatient Stay, Extension 
Stay, and Follow-up;  
7.3.6 Schedule of Events Table 
Replace the term ‘normal’, ‘normalization’, or ‘defined’ with 
‘acceptable’ or ‘accepted’ in reference to vital signs. 
1 Key Roles 
To update the phone numbers for Sponsor Medical Expert, address for 
the Principal Investigator, update the Medical Monitor name and contact 
information. 
5.2 Participant Exclusion Criteria 
To change the alcohol dependence criteria for exclusion criteria (#8) to 
DSM-5.  
5.2 Participant Exclusion Criteria; 
7.1.1 Study Specific Procedures 
To remove incorrectly defined normal ranges for vital signs, oxygen 
saturation, and respiration rate (#11). 
5.2 Participant Exclusion Criteria; 
7.6 Prohibited Medications, 
Treatments, and Procedures 
To add donation of platelets to the list of exclusionary criteria (#19) and 
prohibited procedures. 
6.1.2 Formulation, Appearance, 
Packaging, and Labeling 
To update the IXT-m200 label information with manufacturing date and 
lot numbers. To update the METH vial information as changed over time 
by the provider NIDA. 
6.1.5 Dosing and Administration 
To update the fluid allowances relative to dose administration for both 
Study Agent and Challenge Agent. To provide the timing for meal 
provision after Study Agent dosing. 
6.2 Study Agent Accountability 
Procedures 
To allow for multiple shipments of METH if the first shipment is not 
adequate to complete the study due to expiration date or higher than 
expected subject retention and use. 
7.1.1 Study Specific Procedures;  
To note that subjects should be resting supine for 5 min prior to vital sign 
collection, and to update the timing of the pre-dose collection point. 
7.1.1 Study Specific Procedures; 
7.2.3 Specimen Preparation, 
Handling, and Storage; 
7.2.4 Specimen Shipment 
To note that samples will be processed, stored, and shipped per 
laboratory manual. 
7.1.1 Study Specific Procedures 
Update list of questions to be included in the DEQ and the questions that 
will be used to determine appropriate subjective responses on Day 1. 
This was done to shorten the time necessary for completion and to make 
it more comparable to similar studies. 
7.2.1 Clinical Laboratory 
Evaluations 
To clarify the requirements for quantitative urinalysis, reduce the 
frequency of pregnancy tests to approximately monthly, and to add 
screening serology details. 
7.2.1 Clinical Laboratory 
Evaluations; 
7.3.6 Schedule of Events Table 
To add the analysis of cytokines to the clinical laboratory evaluation list 
and schedule of events table so that it is not overlooked. 
7.2.2 Other Assays or Procedures  
Change the processing of blood samples for METH and AMP PK from 
serum to plasma; plasma is more commonly used in human sample 
testing for METH. To update blood and urine collection volumes 
necessary.  
7.3.1 Screening 
To remove ‘nucleic acid’ word duplication. 

iv 
 
 
 
Item or Section(s) 
Justification 
7.3.3 Inpatient Stay, Extension 
Stay, and Follow-up 
To add cytokine sample collection to the events on Inpatient Stay (Day 
4). 
7.3.5 Early Termination Visit 
To clarify that samples will be taken if the subject is willing to stay long 
enough. 
7.3.6 Schedule of Events Table 
To update vital sign, ECG, and DEQ baseline measurement time point; to 
clarify that a 24 hr post-METH time point ECG will be recorded, to 
change the time points for METH PK collections, to add a spot collection 
of urine prior to METH challenge dosing regimen for baseline 
measurement, and to add cytokine sample collection details. 
8.6 Safety Oversight 
To remove the stated frequency of DSMB meetings so that changes may 
be made within the DSMB Charter without requiring a protocol revision, 
and to rearrange the section for clarity of roles. 
10.3 Analysis Datasets 
To remove the Enrolled Population and replace it with a Qualification 
Safety Population for analysis, and to clarify the Safety Population 
description. 
10.4.1 General Approach; 
10.4.2 Analysis of the Primary 
Efficacy Endpoint(s) 
To delete the references to serum concentrations of METH and to 
remove measures that are no longer assessed by the DEQ. 
13.3.1 Consent/Assent and Other 
Informational Documents Provided 
to Participants 
To add that the ICF will state that it is possible that binge use of METH 
after receiving IXT-m200 could be extremely dangerous and possibly 
life-threatening.  
Appendix 
Deleted list of significant changes as it only repeated information from 
this table. 
Version 4 
Effective Date: 16 March 2018 
5.2 Participant Exclusion Criteria 
Updated (#7) to clarify past year suicide attempt and/or suicidal ideation 
are exclusionary. Emphasized PI discretion to exclude any who are 
considered at risk for suicide. 
7.1.1 Study Specific Procedures 
Updated Table 6 to add blood volumes necessary to analyze cytokines. 
Corrected number of samples and resulting volumes for IXT-m200 and 
METH PK collections. 
7.2.1 Clinical Laboratory 
Evaluations 
Removed requirement for quantitative urine glucose testing since blood 
glucose will be determined on the same days as urinalysis testing. 
Version 5 
Effective Date: 30 May 2018 
Schematic of Study Design 
Throughout the protocol hemodynamic results are noted to be evaluated 
at the discretion of the Investigator. The text of ‘pre-defined 
hemodynamic limits’ was inadvertently left in the schematic. 
5.2 Participant Exclusion Criteria’ 
7.3.6 Schedule of Events Table 
By administrative error, SCID-DSM-5 was referenced in this protocol 
while the intention was to only use the DSM-5 criteria for evaluating 
drug or alcohol use. Psychiatric evaluation is taken during medical 
history and also includes the C-SSRS. To correct Exclusion criteria #6 
and 7.3.6 footnote ‘b’ as intended, reference to DSM-5 is removed. 
7.2.1 Clinical Laboratory 
Evaluations 
To update the Urinalysis testing requirements. The same tests are to be 
conducted but listed as microscopic rather than macroscopic. 
7.3.1 Screening;  
7.3.6 Schedule of Events Table 
By administrative error, SCID-DSM-5 was referenced in this protocol 
while the intention was to only use the DSM-5 criteria for evaluating 
drug or alcohol use. Reference to SCID is removed. 

v 
 
Item or Section(s) 
Justification 
7.3.2 Enrollment/Baseline;  
7.3.3 Inpatient Stay, Extension 
Stay, and Follow-Up;  
7.3.5 Early Termination Visit 
Assessments of METH use should be made ‘since last visit’ rather than 
‘past 30 days’ to allow for coverage between missed or delayed visits. 
7.3.3 Inpatient Stay, Extension 
Stay, and Follow-Up 
Inserted the parenthetical (Day 105 only) under ‘Outpatient Follow-up 
(Days 84, 105 [±3 days])’ to match the previously updated footnote ‘a’ in 
7.3.6. 
7.3.6 Schedule of Events Table 
The Day 5 pre-dose ECG will collect the same data as the Day 4 24 hour 
ECG, thus both are not required. Correction was made to footnote g to 
indicate which one will be done. 
Version 6 
Effective Date: 26 Apr 2019 
Statement of Compliance; 
Protocol Summary; 
1 Key Roles; 
5.4.1 Reasons for Withdrawal or 
Termination; 
6.2 Study Agent Accountability 
Procedures; 
7.2.1 Clinical Laboratory 
Evaluations; 
7.3.1 Screening; 
7.7 Rescue Medications, 
Treatments, and Procedures; 
8.5 Study Halting Rules; 
8.6 Safety Oversight; 
9 Clinical Monitoring; 
11 Source Documents and Access 
to Source Data/Documents; 
12 Quality Assurance and Quality 
Control; 
14.3 Protocol Deviations; 
13.4 Participant and Data 
Confidentiality; 
14.1 Data collection and 
Management Responsibility 
Minor edits to text to accommodate the addition of Anaheim Clinical 
Trials site. 
1 Key Roles 
Updated Sponsor’s Medical Expert phone number. 
5.3 Strategies for Recruitment and 
Retention 
Added additional options for transportation of subjects to site. 
6.1.1 Acquisition 
Removed specified shipper of IXT-m200 vials. 
7.3.1 Screening; 
7.3.3 Inpatient Stay, Extension 
Stay, and Follow-up 
Clarified that DSM-5 criteria would be used to diagnose SUDs at 
Screening and to assess severity during certain follow-ups, and that 
assessments of METH and other drug use would be performed 
separately. 
7.3.3 Inpatient Stay, Extension 
Stay, and Follow-up 
Added text for specific questions to be asked of subjects who affirm their 
use of METH since the last visit. Incorporates changes from 
Administrative Letter dated 28 Jun 2018. 
7.3.6 Schedule of Events Table 
Updated footnotes ‘l’ and ‘k’ to add time windows around the PK sample 
collection points per Administrative Letter 2 dated 15 Aug 2018. 

vi 
 
 
 
 
 
Item or Section(s) 
Justification 
8.2.2 Relationship to Study Agent 
Removed statement “Causality of the AEs are not part of the 
discontinuation criteria or of determining drug related toxicity unless it is 
clearly unrelated to study drug administration.” due to ambiguity. 
15.1 Study Leadership 
Removed the annual meeting requirement and allowed for ad hoc 
meetings instead. 
Version 7 
Effective Date: 10 Jul 2019 
Schematic of Study Design 
Change the number of subjects per dose group in Cohort 3. 
1 Key Roles 
Corrected the zip codes for Anaheim site and Medical Monitor. 
4.1 Description of the Study 
Design 
The purpose for updating the STAMPOUT protocol to version 7 is to 
adjust the dose level ratio for cohort 3 to reflect study performance to 
date. Enrollment has been completed in cohorts 1 and 2. The unblinded 
statistician has reported that more than 10 subjects in the 6 mg/kg group 
have completed Day 22 which means the target number for the low dose 
group has been exceeded. The amendment adjusts the cohort 3 
configuration from 12 - placebo, 12 - 6 mg/kg, 12 – 20 mg/kg to 12 – 
placebo, 24 – 20 mg/kg. There are no additional anticipated safety risks 
based on interim safety data; there have been no SAEs, nor any AEs 
above Grade 2. The reason for the large initial number of enrollees was 
to compensate for the high expected early (prior to Day 22) dropout rate, 
which has not been realized. By dropping the collection of additional, 
and unnecessary, subjects in the low dose group, we will have a better 
chance of reaching our target enrollment in the high dose group and 
completing the study successfully. 
Version 8 
Effective Date: 06 Aug 2019 
4.1.1 Primary Endpoint 
Corrected ‘serum’ to ‘plasma’ as METH concentrations are determined 
in plasma samples. 
5.2 Participant Exclusion Criteria 
Added ‘(nicotine only)’ to criterion #9 to clarify that marijuana is not 
allowed during the inpatient stay. 
7.1.1 Study Specific Procedures 
Under Psychiatric Evaluation, text was added to specify the definition of 
a significant finding on the C-SSRS. A sentence was also added to allow 
for ad hoc administration of the C-SSRS if indicated. 
7.2.1 Clinical Laboratory 
Evaluations 
Replaced ‘Quest Diagnostic’ with ‘Local lab’ as both sites will be using 
their own local lab. Also deleted the term ‘E subunit’ from the pregnancy 
test description as it was incorrect. 
7.7 Rescue Medications, 
Treatments, and Procedures 
Descriptions of treatment for METH withdrawal and psychosis were 
added. 
14.1 Data Collection and 
Management Responsibilities 
Text added to clarify that each Investigator will keep their own study 
files in appropriate facilities. 
Version 9 
Effective Date: 20 Aug 2019 
2.2 Rationale; 
6.1.4 Preparation 
Reference to a ‘maximum dose of 1500 mg’ has been deleted throughout 
the protocol. The previous version of the protocol may have been 
confusing at a site level because it allowed up to 20 mg/kg IXT-m200 
and up to 100 kg body weight (2000 mg IXT-m200), but limited the 
maximum dose to 1500 mg.  

vii 
 
TABLE OF CONTENTS 
 
SUMMARY OF CHANGES AND JUSTIFICATIONS .............................................................................. ii 
TABLE OF CONTENTS ............................................................................................................................. vi 
LIST OF ABBREVIATIONS ....................................................................................................................... 1 
STATEMENT OF COMPLIANCE – PRA Health Sciences ....................................................................... 3 
STATEMENT OF COMPLIANCE – Anaheim Clinical Trials ................................................................... 4 
PROTOCOL SUMMARY ............................................................................................................................ 5 
SCHEMATIC OF STUDY DESIGN ........................................................................................................... 6 
1 
KEY ROLES .......................................................................................................................................... 7 
2 
INTRODUCTION .................................................................................................................................. 8 
2.1 
Background Information ............................................................................................................... 8 
2.2 
Rationale ..................................................................................................................................... 12 
2.3 
Potential Risks and Benefits ....................................................................................................... 15 
2.3.1 
Known Potential Risks ................................................................................................... 15 
2.3.2 
Known Potential Benefits ............................................................................................... 17 
3 
OBJECTIVES AND PURPOSE .......................................................................................................... 18 
4 
STUDY DESIGN AND ENDPOINTS ................................................................................................ 18 
4.1 
Description of the Study Design ................................................................................................. 18 
4.1.1 
Primary Endpoint ........................................................................................................... 19 
4.1.2 
Secondary Endpoints ...................................................................................................... 19 
5 
STUDY ENROLLMENT AND WITHDRAWAL .............................................................................. 19 
5.1 
Participant Inclusion Criteria ...................................................................................................... 19 
5.2 
Participant Exclusion Criteria ..................................................................................................... 20 
5.3 
Strategies for Recruitment and Retention ................................................................................... 21 
5.4 
Participant Withdrawal or Termination ...................................................................................... 22 
5.4.1 
Reasons for Withdrawal or Termination ........................................................................ 22 
5.4.2 
Handling of Participant Withdrawals or Termination .................................................... 22 
5.5 
Premature Termination or Suspension of Study ......................................................................... 22 
6 
STUDY AGENT .................................................................................................................................. 23 
6.1 
Study Agent(s) and Control Description .................................................................................... 23 
6.1.1 
Acquisition ..................................................................................................................... 23 
6.1.2 
Formulation, Appearance, Packaging, and Labeling ...................................................... 23 
6.1.3 
Product Storage and Stability ......................................................................................... 24 
6.1.4 
Preparation ..................................................................................................................... 24 
6.1.5 
Dosing and Administration ............................................................................................ 24 
6.1.6 
Route of Administration ................................................................................................. 25 
6.1.7 
Starting Dose and Dose Escalation Schedule ................................................................. 25 
6.1.8 
Dose Adjustments/Modifications/Delays ....................................................................... 25 
6.1.9 
Duration of Therapy ....................................................................................................... 26 
6.1.10 Tracking of Dose ............................................................................................................ 26 
6.2 
Study Agent Accountability Procedures ..................................................................................... 26 
7 
STUDY PROCEDURES AND SCHEDULE ...................................................................................... 26 
7.1 
Study Procedures/Evaluations .................................................................................................... 26 
7.1.1 
Study Specific Procedures .............................................................................................. 26 
7.2 
Laboratory Procedures/Evaluations ............................................................................................ 28 
7.2.1 
Clinical Laboratory Evaluations ..................................................................................... 28 
7.2.2 
Other Assays or Procedures ........................................................................................... 29 
7.2.3 
Specimen Preparation, Handling, and Storage ............................................................... 30 
7.2.4 
Specimen Shipment ........................................................................................................ 30 

viii 
 
7.3 
Study Schedule ........................................................................................................................... 30 
7.3.1 
Screening ........................................................................................................................ 30 
7.3.2 
Enrollment/Baseline ....................................................................................................... 30 
7.3.3 
Inpatient Stay, Extension Stay, and Follow-up .............................................................. 31 
7.3.4 
Final Study Visit ............................................................................................................. 33 
7.3.5 
Early Termination Visit .................................................................................................. 33 
7.3.6 
Schedule of Events Table ............................................................................................... 34 
7.4 
Justification for Sensitive Procedures ......................................................................................... 37 
7.5 
Concomitant Medications, Treatments, and Procedures ............................................................ 37 
7.5.1 
Precautionary Medications, Treatments, and Procedures ............................................... 37 
7.6 
Prohibited Medications, Treatments, and Procedures ................................................................ 37 
7.7 
Rescue Medications, Treatments, and Procedures ...................................................................... 37 
7.8 
Participant Access to Study Agent At Study Closure ................................................................. 39 
8 
ASSESSMENT OF SAFETY .............................................................................................................. 39 
8.1 
Specification of Safety Parameters ............................................................................................. 39 
8.1.1 
Definition of Adverse Events ......................................................................................... 39 
8.1.2 
Definition of Serious Adverse Events ............................................................................ 39 
8.1.3 
Definition of Unanticipated Problems ............................................................................ 40 
8.2 
Classification of an Adverse Event ............................................................................................. 40 
8.2.1 
Severity of Event ............................................................................................................ 40 
8.2.2 
Relationship to Study Agent ........................................................................................... 41 
8.2.3 
Expectedness .................................................................................................................. 41 
8.3 
Time Period and Frequency for Event Assessment and Follow-Up ........................................... 41 
8.4 
Reporting Procedures ................................................................................................................. 42 
8.4.1 
Adverse Event Reporting ............................................................................................... 42 
8.4.2 
Serious Adverse Event Reporting .................................................................................. 42 
8.4.3 
Reporting of Pregnancy .................................................................................................. 43 
8.5 
Study Halting Rules .................................................................................................................... 43 
8.6 
Safety Oversight ......................................................................................................................... 43 
9 
CLINICAL MONITORING ................................................................................................................. 44 
10 STATISTICAL CONSIDERATIONS ................................................................................................. 45 
10.1 Statistical and Analytical Plans .................................................................................................. 45 
10.2 Statistical Hypotheses ................................................................................................................. 45 
10.3 Analysis Datasets ........................................................................................................................ 45 
10.4 Description of Statistical Methods .............................................................................................. 45 
10.4.1 General Approach........................................................................................................... 45 
10.4.2 Analysis of the Primary Efficacy Endpoint(s) ................................................................ 46 
10.4.3 Analysis of the Secondary Endpoint(s) .......................................................................... 47 
10.4.4 Safety Analyses .............................................................................................................. 47 
10.4.5 Adherence and Retention Analyses ................................................................................ 48 
10.4.6 Baseline Descriptive Statistics ....................................................................................... 48 
10.4.7 Multiple Comparison/Multiplicity ................................................................................. 48 
10.5 Sample Size ................................................................................................................................ 48 
10.6 Measures to Minimize Bias ........................................................................................................ 48 
10.6.1 Enrollment/ Randomization/ Masking Procedures ......................................................... 48 
10.6.2 Breaking the Study Blind/Participant Code ................................................................... 48 
11 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .............................. 49 
12 QUALITY ASSURANCE AND QUALITY CONTROL ................................................................... 49 
13 ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................................ 50 
13.1 Ethical Standard .......................................................................................................................... 50 
13.2 Institutional Review Board ......................................................................................................... 50 

ix 
 
13.3 Informed Consent Process .......................................................................................................... 50 
13.3.1 Consent/Assent and Other Informational Documents Provided to Participants ............. 50 
13.3.2 Consent Procedures and Documentation ........................................................................ 51 
13.4 Participant and Data Confidentiality .......................................................................................... 52 
13.4.1 Research Use of Stored Human Samples, Specimens or Data ....................................... 52 
13.5 Future Use of Stored Specimens................................................................................................. 52 
14 DATA HANDLING AND RECORD KEEPING ................................................................................ 53 
14.1 Data Collection and Management Responsibilities .................................................................... 53 
14.2 Study Records Retention ............................................................................................................ 53 
14.3 Protocol Deviations .................................................................................................................... 54 
14.4 Publication and Data Sharing Policy .......................................................................................... 54 
15 STUDY ADMINISTRATION ............................................................................................................. 54 
15.1 Study Leadership ........................................................................................................................ 54 
16 CONFLICT OF INTEREST POLICY ................................................................................................. 55 
17 LITERATURE REFERENCES ........................................................................................................... 56 
 

STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy 
Version 9 
M200C-1801 
 
20 Aug 2019 
 
 
1 
LIST OF ABBREVIATIONS 
 
Abbreviation 
Meaning 
AE 
adverse event 
ALT 
alanine aminotransferase 
ALP 
alkaline phosphatase 
AMP 
amphetamine 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
BMI 
body mass index 
bpm 
beats per minute 
CFR 
Code of Federal Regulations 
ch-mAb7F9 
See IXT-m200 
CNS 
central nervous system 
CP1 2010 
Club Phase 1 working group grading scale recommendations published in 2010 
CPK 
creatine phosphokinase  
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV% 
coefficient of variation 
DEQ 
drug effects questionnaire 
DLT 
dose limiting toxicity 
DSMB 
Data and Safety Monitoring Board 
DSM-V or –IV 
Diagnostic and Statistical Manual of Mental Disorders 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
ELISA 
enzyme linked immunosorbent assay  
FDA 
Food and Drug Administration 
GCP 
good clinical practices 
GI 
gastrointestinal 
HACA 
human anti-chimeric antibody 
HBsAG 
hepatitis B surface antigen 
HepC 
hepatitis C 
HIV 
human immunodeficiency virus 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
IRB 
Institutional Review Board 
IV 
intravenous 
IXT-m200 
chimeric anti-methamphetamine antibody, also called ch-mAb7F9 
mAb 
monoclonal antibody 
mAb7F9 
murine form of IXT-m200, or ch-mAb7F9 
MDMA 
3,4-methylenedioxymethamphetamine, also called ecstasy 
METH 
methamphetamine 
mol-eq 
molar equivalent, also mol-equiv 
N 
number 
NAT 
nucleic acid testing 
NIDA 
National Institute on Drug Abuse 

STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy 
Version 9 
M200C-1801 
 
20 Aug 2019 
 
 
2 
Abbreviation 
Meaning 
NIH 
National Institutes of Health 
PBO 
placebo 
PD 
pharmacodynamic 
PI 
Principal Investigator 
PK 
pharmacokinetic 
QC 
quality control 
RBC 
red blood cell 
SA 
self-administration 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
sc 
subcutaneous 
SCID 
structured clinical interview for diagnosis 
SD 
standard deviation 
SEM 
standard error of the mean 
SMC 
safety monitoring committee 
SOP 
standard operating procedure 
t1/2  
elimination half-life 
THC 
tetrahydrocannabinol 
TOA62936 
Phase 1a study of IXT-m200  
Vd 
volume of distribution 
WBC 
white blood cell 
 
 
 
 

STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy 
Version 9 
M200C-1801 
 
20 Aug 2019 
 
 
5 
PROTOCOL SUMMARY 
Title: 
STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy 
Summary: 
This is a parallel-group, placebo-controlled, double-blind safety study of IXT-m200 
in otherwise healthy subjects with methamphetamine (METH) use disorders. An 
adequate number of subjects will be enrolled to ensure approximately 42 
completers. Four cohorts will receive single doses of IXT-m200 (6 or 20 mg/kg) or 
placebo followed by a series of weekly METH challenges during a 23-day inpatient 
stay.  
Subjects who successfully complete study procedures through Day 22 may 
continue into an optional Inpatient Extension for an additional 7-day duration 
(through Day 29).  
Outpatient follow-up visits will continue through Day 126. Changes in METH 
effects, as well as safety, pharmacokinetics (PK) of IXT-m200 and METH, and 
immunogenicity will be analyzed.  
Objectives: 
 
Primary Objective: To determine the effect of IXT-m200 on METH PK parameters 
relative to placebo. 
 
Secondary Objectives: To determine the effect of IXT-m200 on METH subjective 
effects, and to evaluate the safety and tolerability and PK of single, intravenous 
(IV) doses of IXT-m200 relative to placebo followed by weekly IV METH 
challenges in subjects with METH use disorders. 
Endpoint 
Primary Endpoint:  
 
Change in serum METH area under the concentration-time curve (AUC) or 
Cmax resulting from METH challenge doses following single IV doses of 
IXT-m200. 
Secondary Endpoints:  
 
Change in subjective effects of METH challenge doses as measured by drug 
effects questionnaires (DEQ; ie, reduction of ‘High’). 
 
Safety and tolerability of IXT-m200 followed by METH challenges as 
measured by physical examinations and vital sign, adverse event (AE), 
electrocardiogram (ECG), clinical laboratory testing, and immune response by 
measurement of anti-IXT-m200 antibody levels. 
 
Pharmacokinetics of IXT-m200 following single administration. 
Population: 
Approximately 126, generally healthy males and females aged 21-50,  
non-treatment seeking, METH-using subjects who have METH use disorders will 
be recruited to retain 42 completed subjects. 
Phase: 
2a 
Number of 
Sites: 
2 - PRA Health Sciences, Salt Lake City, UT;  
Anaheim Clinical Trials, Anaheim, CA 
Description of 
Study Agent: 
IXT-m200 is a chimeric anti-methamphetamine monoclonal antibody. Doses will 
be 6 or 20 mg/kg given by 2 hour IV infusion. 
Challenge Agent: (+)-Methamphetamine hydrochloride (METH; 30 mg) will be 
administered by IV bolus administration over 2 minutes. 
Placebo: commercially available normal saline for use as placebo for IXT-m200 
and METH. 

STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy 
Version 9 
M200C-1801 
 
20 Aug 2019 
 
 
6 
Study 
Duration: 
18 months 
Participant 
Duration: 
4.5 months 
 
 
SCHEMATIC OF STUDY DESIGN 
Prior to 
Enrollment 
Obtain informed consent. Screen potential subjects by inclusion and exclusion criteria; 
obtain history and document.  
 
 
Day -1 to 1    
Perform baseline assessments on Day -1. Admit if acceptable. On Day 1, administer METH 
challenge dose regimen (placebo and 30 mg IV METH given 4 hours apart) with vital signs 
and cardiovascular monitoring, and DEQ for METH effects. Randomize subjects whose 
responses are within acceptable hemodynamic limits based on the discretion of the 
Investigator and also provide appropriate DEQ responses; discharge those who do not pass 
the discrimination test. See Section 7.3.6 Schedule of Events Table for details. 
Day 2 to 3 
 
Doses 
shown are 
IXT-m200 
 
Day 4 
Administer IXT-m200 or placebo as an IV infusion over 2 hours. Monitor by vital signs 
and telemetry; take serial blood samples for PK. 
 
 
Days 5, 12, 
and 19 
Administer METH challenge dose regimen (placebo and 30 mg IV METH given 4 hours  
apart in randomized order) with vital signs and cardiovascular monitoring, and DEQ for 
METH effects. Take serial blood samples and collect urine for PK. 
 
 
Day 22 
Obtain informed consent if subject 
wishes to stay for Inpatient 
Extension Stay. 
 
Discharge if exam and vital signs are 
acceptable. 
 
 
Day 26 
Administer METH challenge dose 
regimen (placebo and 30 mg IV 
METH given 4 hours apart in 
 
 
Randomize Cohorts Sequentially 
Cohort 1 
6 mg/kg (n=12) 
Placebo (n=6) 
Cohort 2 
6 mg/kg (n=6) 
20 mg/kg (n=6) 
Placebo (n=6) 
Cohort 3 
20 mg/kg (n=24) 
Placebo (n=12) 
 
Cohort 4 
20 mg/kg (n=36) 
Placebo (n=18) 
Inpatient Extension or Follow-up 

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randomized order) with vital signs 
and cardiovascular monitoring, and 
DEQ for METH effects. Take serial 
blood samples for PK. 
 
 
Day 29/28 
Discharge if exam and vital signs 
are acceptable. 
 
Weekly follow-up assessments of 
study endpoints and safety. 
 
 
Days 35, 
42, 49, 56, 
63 (±2d) 
Weekly follow-up assessments of study endpoints and safety.  
 
 
 
Days 84 
and 105 
(±3d) 
Follow-up assessments of study endpoints and safety.  
 
 
 
Day 126 
(±3d) 
Final visit and assessment of study endpoints and safety.  
 
 
1 
KEY ROLES 
 
Sponsor 
InterveXion Therapeutics, LLC 
4301 W. Markham St. #831, Little Rock, AR 72205 
Sponsor’s Medical Expert 
W. Brooks Gentry, MD, Chief Medical Officer 
InterveXion Therapeutics, LLC 
4301 W. Markham, Slot 831 Little Rock, AR, 72205 
(501) 320-7601 (office) 
gentrywilliamb@uams.edu 
Principal Investigator - 
PRA 
Lynn Webster, MD,Vice President of Scientific Affairs, Early 
Development Services, PRA Health Sciences  
1255 East 3900 South, Salt Lake City, UT 84124 
(801) 904-4593 (office), (801) 560-1707 (cell) 
WebsterLynn@prahs.com 
Principal Investigator - 
ACT 
Peter Winkle, MD 
Anaheim Clinical Trials 
1085 N Harbor Boulevard, Anaheim, CA 92801 
(714) 774-7777 
pwinkle@act-trials.com 
Clinical Research Unit 
Medical Monitor 
Stephen Zukin, MD, Medical Director, Psychiatry - Medical Affairs 
PRA Health Sciences 
731 Arbor Way, Suite 100, Blue Bell, PA 19422 
(214) 591-1240 (office) 
ZukinStephen@prahs.com 

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2 
INTRODUCTION  
 
2.1 
BACKGROUND INFORMATION  
 
Study Agent 
IXT-m200, also called ch-mAb7F9, is a chimeric monoclonal antibody (mAb) that binds METH with 
high affinity. The product contains a murine METH-binding variable region and the constant domains of 
a human immunoglobulin G (IgG) 2κ. This antibody isotype was chosen because of the lower risk of 
immune response compared to an IgG1 or IgG3. IXT-m200 targets METH, does not rely on binding to any 
endogenous target for its action, and was demonstrated to be safe and well tolerated in a previous clinical 
investigation (see below).  
 
Through the binding of METH in the bloodstream, it is anticipated that IXT-m200 will alter the PK of 
METH and decrease concentrations of METH at its active sites in the brain. In an acute setting, the 
presence of IXT-m200 should therefore decrease the perceived pleasurable effects of METH. Over the 
longer term, when combined with conventional behavior modification therapy, IXT-m200 should reduce 
the frequency of METH use over time. 
 
Nonclinical Summary 
A significant body of nonclinical work in rats indicates that IXT-m200 may be effective as a treatment for 
METH use disorders. The potential human efficacy of IXT-m200 is demonstrated by 5 important  
in vivo preclinical studies using the murine version of the antibody, called mAb7F9. The studies and 
results are summarized in Table 1. 
 
Table 1. Summary of nonclinical studies in rats with mAb7F9 
Study ID 
Description 
Brief Summary of Results 
SMO/EML-
2194 
 
Owens et al., 
20111 
Long-term in vivo function 
of mAb7F9 – mAb7F9 
administered once after first 
24 hours of a 2 week 
continuous sc METH 
infusion 
MAb7F9 was administered at a dose (180 mg/kg) that provided an 
equal number of binding sites to METH molecules in the body. 
MAb7F9 redistributed and retained METH in the serum (shown by 
increased METH serum concentrations) throughout the 2 weeks 
even though the mAb was outnumbered by METH after the first 
hour.  
WBG-2787 
 
Laurenzana et 
al., 20142 
Effects on METH stimulated 
locomotor activity and 
rearing in an overdose model 
– mAb7F9 administered 30 
minutes after a 1 mg/kg IV 
METH dose 
MAb7F9 reduces distance traveled at less than molar equivalent 
(mol-eq) doses to METH molecules (Figure 1). Duration of METH 
effects and number of rearing events were reduced at equimolar 
dosing. Peak activity was reduced immediately after 
administration, significantly at the 1 mol-eq dose. METH Vd and 
clearance were reduced, with a proportional METH t1/2λz increase 
following 1 and 0.32 mol-eq doses.  
SMO/VCU-
0001 
 
Beardsley et 
al., manuscript 
in prep 
Relapse/reinstatement testing 
in a SA model - mAb7F9 
was used to block/reduce 
continuation of METH-
primed relapse to METH SA 
Following SA training and extinction, mAb7F9 produced 
dose-dependent changes in number of presses on a disconnected 
lever following a METH priming dose. 30 mg/kg mAb7F9 did not 
change the baseline response, 56 mg/kg resulted in non-significant 
increased responding, and 100 mg/kg produced significant 
decreased responding following the third mAb dose (Figure 2). 
SMO/MH-
3015 
 
Hambuchen et 
al., 20143 
Repeated mAb7F9 dosing 
with effects on METH 
stimulated locomotor 
activity and rearing 
MAb7F9 loading dose followed by 2 weekly (141 mg/kg) 
administrations reduced 0.56 mg/kg METH-induced horizontal 
locomotion and rearing throughout dosing during the 60-120 
minute post METH interval. MAb7F9 treatment also decreased 
duration of 1.68 mg/kg METH-induced behaviors 10 and 14 days 
after discontinuation of mAb treatment (Figure 3). 

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Study ID 
Description 
Brief Summary of Results 
WBG-3013 
 
Stevens et al., 
20144 
Bioequivalence testing of 
mAb7F9 vs. IXT-m200 
effects on METH PK 
MAb7F9 and IXT-m200 produce similar METH PK changes as 
expected. Ligand cross reactivity studies suggest IXT-m200 will 
not bind to endogenous molecules or other medications. 
hrs = hours; IV = intravenous; mAb7F9 = murine form of IXT-m200, or ch-mAb7F9; METH  = methamphetamine; 
mol-eq = molar equivalent; PK = pharmacokinetic; SA = self-administration; sc = subcutaneous; SD = standard 
deviation; SEM = standard error of the mean. 
 
 
Figure 1. METH effects were reduced by mAb7F9. The left panel shows the distance traveled (±SD) by rats (n=6) 
dosed with METH only (open circles) or METH plus 1 mol-eq mAb7F9 (closed circles). Baseline behavior was 
recorded between -60 to -30 min. METH was given at -30 minutes followed by mAb administration at time 0. The 
right panel shows the results quantified from all 4 mAb7F9 doses. * = P <0.05 vs. saline for that mAb dose. 
 
 
 
Figure 2. Active lever presses by rats (n=12) during 
self-administration sessions when mAb was 
administered 6 hrs prior to the session (Days 1, 4, & 7) 
and when mAb was not administered (Days 10 & 13), 
in groups treated with 100 mg/kg mAb7F9 (filled 
circles) or saline (open circles). Bars show ±SEM. The 
asterisk represents a significantly different value from 
the saline control group during the same session 
(p<0.05). 
Figure 3. Distance traveled over time (+SD) after a 
1.68 mg/kg METH dose given at time 0 in mAb7F9 
(closed circles, n=5) and vehicle-treated (open circles, 
n=6) rats 14 days after the last of 3 mAb doses. The 
best-fit linear regression line (in red) was fit to the 
terminal portion of the horizontal locomotion-time curve. 
This line estimated the termination of activity and 
therefore the relative difference in the duration of METH 
effects between treatment groups.  
 
-100
0
100
200
300
0
400
800
1200
1600
Time (min)
Distance Traveled (avg cm)
Distance traveled 
ò64%
Saline
mAb7F9
1.00
0.56
0.32
0.10
0
200
400
600
800
mol-equiv dose of METH binding sites:METH
Total distance traveled (m)
Saline
mAb7F9
*
*
*
Day 1
Day 4
Day 7
Day 10
Day 13
0
25
50
75
100
# Lever Presses
Saline
mAb7F9
mAb
no mAb
*
0
120
240
360
0
800
1600
2400
Time (min)
Distance Traveled (cm)
Duration of effect
ò31%
Saline
mAb7F9

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Nonclinical Studies Supporting the Current Clinical Protocol 
A series of 4 nonclinical studies were completed in rats to address the potential for IXT-m200 to 
exacerbate METH effects. These studies were designed to identify potential toxicities resulting from 
higher blood concentrations of METH in the presence of IXT-m200, or from increased METH self-
administration (SA) by a user in an effort to overcome the reduction of METH effects by the antibody.   
 
In each of the 4 studies, rats were acclimated to high doses of METH over a 14-day period to make them 
tolerant to high doses of METH, similar to what occurs in human chronic METH users. By the last day, 
rats survived three 4 mg/kg doses of METH spaced 4 hours apart. Three days later (Day 17), rats were 
dosed with 0, 5, or 20 mg/kg IXT-m200. The following day, a series of METH binges used to simulate a 
patient’s attempts to surmount the antibody’s effects was initiated. On Day 18, rats were given 4 doses of 
METH 6 mg/kg spaced 2 hours apart. This binge dosing regimen was repeated on Days 21 and 24 for 
certain studies and groups. 
 
The 4 studies (GLP toxicology, cardiovascular effects, METH PK, and METH distribution) collected 
different outcome measurements while using the same METH administration protocol. Results are 
summarized below (Table 2).  
 
Table 2. Summary of nonclinical studies supporting testing in METH users 
Study reference 
Summary of end points and results 
20099217 - GLP 
toxicology  
 
This study evaluated clinical signs, body weights, body weight gain, food 
consumption, ophthalmology, clinical pathology parameters (hematology, 
coagulation, clinical chemistry, and urinalysis), toxicokinetic parameters, gross 
necropsy findings, organ weights, and histopathologic examinations. 
 
No IXT-m200-related mortality or target organs were identified. There were 
early deaths attributed to high doses of METH in all groups. 
 
There were no IXT-m200-related clinical signs or changes in food 
consumption, ophthalmology, clinical chemistry parameters, urinalysis 
parameters, or corticosterone levels in this study. There were no  
IXT-m200-related organ weight changes, macroscopic pathology observations, 
or microscopic observations. Findings present among animals that died prior to 
scheduled termination were consistent with METH toxicity. 
 
Systemic exposure to METH during the METH binge regimen increased with 
increasing dose of IXT-m200, but was less than dose proportional. 
 
2 of 13 animals given 20 mg/kg IXT-m200 screened positive for 
immunogenicity on Day 54. 
20098702 - 
Safety 
Pharmacology 
(Cardiovascular 
effects) 
 
This study evaluated cardiovascular parameters and body temperature/activity 
by telemetry, clinical signs, body weights and gains, food consumption, 
toxicokinetic parameters, gross necropsy findings, and organ weights. 
 
Following administration of IXT-m200, four telemetered animals died after 
METH binge dosing. All were considered related to the high doses of METH 
administered. 
 
METH challenges on Days 18, 21, and 24 were associated with increased 
activity, body temperature, heart rate, and blood pressure; there was a trend 
toward attenuated blood pressure response at 20 mg/kg IXT-m200 only on 
Days 18 and 21 (but not on Day 24).  
 
Minor changes in organ weights were present that had a dose-dependent trend, 
including increased liver, prostate, thymus, and thyroid weights and organ to 
body/brain weight ratios, but the toxicological relevance of these changes was 

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undetermined as no histological evaluation was performed. 
20106937 -  
GLP METH PK 
 
This study evaluated clinical signs, body weights, body weight gain, limited 
functional observational battery, PK parameters, and gross necropsy findings. 
 
No IXT-m200-related mortality or clinical signs were observed. 
 
There were no major differences in METH exposure between male and female 
rats, though female area under the concentration-time curve (AUC) was higher 
on all binge Days and at all antibody dose levels.  
 
The AUC of METH trended higher with increasing IXT-m200 dose level as 
expected. 
2429-002 -  
METH 
Distribution 
 
This study evaluated radiolabeled METH serum PK parameters, rates and 
routes of excretion, and tissue distribution on Day 18. 
 
IXT-m200 altered serum PK of 14C-METH as expected by increasing the 
maximum concentration (Cmax). IXT-m200 did not notably change the 
excretion of 14C-METH.  
 
Quantitative Whole Body Autoradiography (QWBA) images were analyzed to 
determine the effects of IXT-m200 on the tissue distribution of 14C-METH. At 
30 min post-METH dose, data in males indicates the highest relative METH 
concentrations were kidney > ex- and intra-orbital lacrimal glands > spleen > 
submaxillary gland > liver. Females were similar.  
 
Based on QWBA data collected over 72 hours, IXT-m200 does not appear to 
markedly change the relative distribution of METH administered at extremely 
high levels (6 mg/kg), though clearance from tissues may be increased by the 
presence of antibody.  
 
Clinical Research Summary 
A Phase 1a study of the safety of single doses of IXT-m200 in healthy humans was completed in 2013.5 
In this first clinical study, 42 subjects (17 females) were dosed in 5 groups (0.2, 0.6, 2, 6, and 20 mg/kg 
IXT-m200), with 10 subjects receiving placebo (saline). Pharmacokinetic results indicate that IXT-m200 
is similar to other IgGs, with an elimination half-life of ~18 days, volume of distribution (Vd)  of ~5 L and 
elimination clearance of ~200 mL/d. The disposition of IXT-m200 does not appear to be affected by dose.  
 
There were no serious adverse events (SAEs) or serious adverse reactions during the conduct of the study. 
Only 1 AE was definitely attributed to IXT-m200. A single subject experienced a Common Terminology 
Criteria for Adverse Events (CTCAE v.4.0) Grade 3 infusion reaction half-way through the IXT-m200 
infusion. The subject experienced a brief period of bronchospasm, in which the subject and PI heard a 
single expiratory wheeze. The infusion was stopped and the subject was treated with solu-medrol and 
diphenhydramine. No further symptoms were noted. The subject required outpatient therapy later for 
bronchitis. Because the infusion reaction and bronchitis were mild and short-lived, the study continued 
with no protocol changes.  
 
Samples from all subjects were tested for immunogenicity, ie, anti-IXT-m200 antibodies. Samples from 
only 4 (12.5%) IXT-m200 treated subjects were confirmed to have low titers. One of these 4 subjects also 
provided a predose sample that screened positive for anti-IXT-m200 antibodies. The development of anti-
IXT-m200 antibodies did not appear to be dose-related. 
 
Overall there were no apparent safety or tolerability concerns identified when IXT-m200 was dosed over 
the range from 0.2 to 20 mg/kg. Therefore, a maximum tolerated dose was not reached.  
 

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Relevant Literature 
Results from the Phase 1a study of IXT-m200 were published in Stevens et al., 2014.5 In addition, many 
of the nonclinical studies using mAb7F9 (Table 1), and the studies with IXT-m200 (Table 2), have been 
described above with references where available. We are not aware of other clinical studies of an 
anti-METH mAb or vaccine. 
 
Clinical studies of vaccines against other drugs of abuse such as nicotine and cocaine have been 
published.6-11  However, these have typically been unsuccessful due to the inability to generate sufficient 
antibody titers against the target drug. A mAb can be dosed to high/sufficient levels as it does not rely on 
the immune system of the patient for antibody production as does a vaccine. 
 
Context of the Study 
As there are no approved medications for the treatment of METH use disorders, any progress in the field 
is important. The National Institute on Drug Abuse (NIDA) reports that the most effective current 
treatments for METH addiction are behavioral therapies, such as cognitive-behavioral and 
contingency-management interventions. IXT-m200 is ultimately intended to be administered in 
conjunction with behavioral therapy to provide protection against reinforcing effects of METH during 
relapse to drug use. However, we first need to determine whether IXT-m200 exhibits the ability to alter 
human METH disposition before initiating studies in combination with behavioral therapy. This will be 
the first clinical study of a medication developed specifically for METH use disorders to be tested in 
human METH users. 
 
2.2 
RATIONALE  
 
Rationale for the Study 
Following the first in human safety study, which has been completed, the clinical development plan for 
IXT-m200 continues with this study to demonstrate the ability to alter METH PK and reduce or prevent 
subjective effects. This is a proof of concept study to show that intended effects of IXT-m200 are indeed 
realized prior to initiating large studies with METH users where IXT-m200 is administered in conjunction 
with behavioral therapy. IXT-m200 is intended to be used for the prevention of relapse to METH use and 
it is believed that modifications in the lifestyle of users will be required. 
 
Further, METH users, even those who are highly motivated to stop their use, are at high risk for 
recidivism to METH use. Any METH-using volunteer who receives a pharmacologic treatment is also 
therefore at risk for recidivist behavior, and some METH users are at risk for engaging in binge use of 
METH, resulting in high doses of METH taken in a short period of time. The possibility exists that if 
users attempt to surmount the effects of IXT-m200 by taking large METH doses that the binding potential 
for METH will be exceeded. Theoretical risks associated with large doses of METH in the presence of the 
antibody include increased free METH concentrations, peripheral (eg, cardiovascular) toxicity, and 
accumulation of METH.  
 
Because of the high recidivism rate and the theoretical risks associated with IXT-m200’s effects on 
METH toxicity, this assessment of the interaction of IXT-m200 with METH will be done prior to further 
studies of the efficacy of IXT-m200. METH is a US Drug Enforcement Administration Schedule II 
controlled substance, and can therefore be given in a human laboratory setting. Studying the impact of 
IXT-m200 on METH effects in a controlled human laboratory setting will give a greater understanding of 
the risks of the interaction of IXT-m200 with METH compared to METH alone and will improve risk 
mitigation strategies for later studies.  
 

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The hypothesis is that administration of IXT-m200 will alter the METH PK parameters (ie, reduce Vd 
and increase serum concentrations thereby increasing Cmax and AUC) and reduce or prevent the subjective 
effects of subsequent METH challenges. Further, we hypothesize that IXT-m200 will be safe and will not 
cause increased METH toxicity compared to METH alone in human METH users. 
 
Justification for Route of Administration 
IXT-m200 will be administered via IV infusion. This is necessary because it is a protein medication and 
would be metabolized to inactive components in the gastrointestinal (GI) tract if administered orally. The 
volume that must be given is too large to allow for intramuscular or subcutaneous (sc) administration. 
Each dose of IXT-m200 will be diluted in 225 ml of saline and given over 2 hours at progressively 
increasing infusion rates (Table 5). This infusion plan has been used successfully in the Phase 1a study of 
IXT-m200.5 This approach to dosing will allow for rapid response to possible dose-dependent toxicity 
because of the incremental increases in total dose over time. 
 
Justification for IXT-m200 Doses 
The active IXT-m200 doses (6 or 20 mg/kg) were selected for this study because they are both potentially 
effective in reducing METH effects. Nonclinical studies in rats suggest that when the antibody is 
administered several days prior to METH challenge administration, the antibody is still effective at 
reducing METH-induced locomotor activity at a ratio of 30 METH molecules per mAb binding site.3 
(This calculation assumes that the METH dose is confined entirely to the blood volume upon 
administration.) 
 
During this Phase 2a study, subjects will receive a single dose of IXT-m200 followed by 4 weekly IV 
challenge doses of 30 mg METH. Using the data from the Phase 1a study of single doses of IXT-m200 in 
humans, we can predict the serum concentrations over time from doses of 6 or 20 mg/kg.  We can also 
estimate the concentration of METH in blood immediately after a 30 mg IV dose as ~36 μM (assuming a 
75 kg person). The minimum concentration of IXT-m200 in serum required to maintain the initial ratio of 
METH to binding sites at 30 is 90 μg/mL (1.2 μM binding sites). Pharmacokinetic simulations of 6 and 
20 mg/kg mAb doses in humans predict that these doses will result in concentrations much greater than 
90 μg/ml. With the 6 mg/kg dose, however, concentrations will drop to 90 μg/ml by 3-4 days after dosing.  
 
Based on these modeled data, the ratio of METH to mAb binding sites will be <30 during the entire set of 
METH challenges after a 20 mg/kg dose.  After a 6 mg/kg dose, the ratio should be <30 during the first 
METH challenge only. Thus, during the second through fourth METH challenges, the effects of 
IXT-m200 will have waned sufficiently that METH challenges will be administered at what is expected to 
be subtherapeutic IXT-m200 levels. A goal of this study is to test the effects of METH challenges on 
IXT-m200 effects as mAb levels decrease to identify the minimum effective serum concentration.   
 
Justification for METH Route of Administration and Doses  
METH will be given via the intravenous (IV) route to increase the reliability and reproducibility of 
subjective (drug effect) responses to METH, and of objective (pharmacokinetic) data describing the 
interaction of IXT-m200 and METH. The METH doses to be used were selected based on METH doses 
that are given commonly to humans in a laboratory setting.12-16 In these previous reports, the doses 
administered were safe and resulted in reliable, measurable responses. Furthermore, there are no data with 
METH that suggest non-treatment seeking METH users increase their METH use after participation in a 
human laboratory study in which IV METH is given. In fact, intravenous-naïve cocaine users given IV 
cocaine injections did not alter their cocaine use frequency or route of administration after the study17 
Nevertheless, subjects who currently use METH via the snorting or oral routes will have to have a history 
of smoking or IV METH use because of the concern that exposure to rapid routes of METH will increase 
risk for escalation of METH use.  
 

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METH doses of 30 mg IV have frequently been given in human laboratory studies.12-16 Single 30 mg IV 
METH doses are associated with significant increases in positive subjective central nervous system 
(CNS) effects and in blood pressure and heart rate. These effects reach maximum values at 30 to 60 
minutes after the dose12 and typically dissipate over 3 to 4 hr.14,18 METH 30 mg IV results in ~20 to 35 
mmHg increases in diastolic blood pressure, 40 mmHg increases in systolic blood pressure, and ~25 beats 
per minute (bpm) increases in heart rate.12,13 The observed CNS and cardiovascular effects are not 
associated with greater risks for AEs than with placebo administration.12 Finally, this dose of METH 
results in measurable changes in subjective effects that can be further shifted by medications to study 
efficacy.13,16 
 
The METH challenge in this study will consist of 2 IV METH doses (0 and 30 mg) separated by 4 hr. The 
subjects will receive a total of 4 METH challenges – at baseline (Day 1), then 3 weekly challenges after 
the single IXT-m200 (or placebo) dose. An additional METH challenge will be given to subjects that 
elect to stay in the unit a week longer. This approach to METH dosing in human subjects has been used in 
other studies,13,15,19 and the dosing regimen allows for pharmacodynamics (PD) and safety assessment of 
METH dose-effects. METH doses will be given intravenously over 2 minutes to standardize the 
administration and to reduce the risk of side effects. 
 
Description of Subjects 
Non-treatment seeking, METH-using subjects who have mild to moderate (2-6 DSM-5 diagnostic 
criteria) DSM-5 METH use disorders will be recruited. If, at any point in their participation in the study, a 
subject indicates a desire for treatment, no more METH challenges will be given to the subject and he/she 
will be referred for treatment. Subjects who begin treatment for their METH use during the study will 
complete all follow-up safety evaluations. 
 
The subjects to be recruited for this study will be non-daily METH users (<30 days per month). While 
there are many patterns of METH use, and it is difficult to quantify, many users take METH from 12 to 
20 times per month.20-22 Furthermore, the subjects in this study should have a stable or regular pattern of 
METH use. In a study of 350 METH users who had undergone treatment, the number of years from 
initiation of METH use until the use pattern was regular was 2.14 years.21  
 
Attempts will be made to recruit METH users who are less likely to engage in binge METH use. In a 
cross-sectional survey study of 451 human immunodeficiency virus (HIV)-negative male and female 
METH users, correlates of binge METH use were determined. The subjects reported using METH on 
average of 14.6 days per month for an average of 13.6 years, with an average age of initiation of 23 years, 
and a monthly average consumption of 9.4 g.20 Approximately 40% of these subjects (183) reported binge 
use, defined as using large quantities for a period of time, until they ran out of METH, or physically could 
not take METH anymore. A multivariate model identified the following factors that were associated with 
METH binge use: 
 
 
Number of days of METH use in the last 30 days (16 vs 13) 
 
History of treatment for METH use  
 
History of engaging in sex marathons while high on METH  
 
History of injection METH use  
 
Higher Beckmans Depression Inventory score (17.2 vs 14.0) 
 
Initiating METH use due a desire to experiment (vs coping or escape, to lose weight or feel more 
attractive, to stay awake or get more energy, or to enhance sex or meet sex partners) 
 
Factors that were not associated with binge use included polydrug use, the average number of years of 
METH use, and the subject’s sex. The full model utilizing the factors above accounted for 10% of the 

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total variance; nevertheless, the factors that were identified were used in developing exclusion criteria, 
including current IV use, to minimize the risk of binge METH use after participation in this study. 
Furthermore, data on the METH use patterns of all subjects will be collected and analyzed, and 
incorporated into an ongoing assessment of risks and recruiting success. 
 
Regular, non-daily METH users who are not interested in or seeking treatment for METH use, and who 
have used METH for more than 2 years will be recruited. The current primary route of SA will be 
smoking, snorting, or oral. Users whose current primary route of SA is snorting or oral will have a history 
of or experience with IV or smoking METH. 
 
Rationale for Selection of This Volunteer Population 
1. While the METH doses to be administered are small, and associated with minimal but measureable 
CNS and cardiovascular effects,12 scientific ethics and the possible risk of promoting METH 
addiction dictate that non-METH users cannot be recruited for this study. Furthermore, the target 
treatment population for IXT-m200 is METH users.  
2. Non-treatment seeking METH users will be recruited for this study because the same ethical 
considerations exist for treatment seeking subjects as for non-METH users. Administration of IV 
METH to non-treatment seeking subjects may increase their risk of progression to IV METH use, but 
it is not certain that this will happen. In a report of residential studies involving administration of 
METH, subsequent psychosocial function and reported drug use were not changed by participation in 
the studies.23  
3. Non-daily METH users are more likely to be able to abstain from METH use for the duration of the 
study. This will minimize the risk for withdrawal from METH which may result from no METH use 
during the study, or from IXT-m200 administration. 
4. Selection of METH users whose primary current route of SA is not IV is important for the following 
reasons. 
a. Non-injection users are less likely to binge on METH, which decreases the likelihood of 
overdose complicating the safety profile of IXT-m200.20 
b. Non-injection users are likely to be healthier than injection METH users.24 At this stage in the 
clinical development of IXT-m200, a greater understanding of the safety profile of IXT-m200 
in relatively healthy subjects is needed prior to administration to subjects with comorbid 
physical illness. 
 
Justification of use of Placebo 
Use of placebo is justified in this study to create a comparator control group who also receives the METH 
challenge doses. Subjects recruited for this study will be non-treatment seeking for their METH use 
disorder. A single dose of IXT-m200 is not likely to benefit subjects who do not wish to change their 
METH intake. The use of placebo, therefore, does not place subjects at further risk nor does it prevent 
them from receiving a likely benefit. 
 
2.3 
POTENTIAL RISKS AND BENEFITS  
 
2.3.1 KNOWN POTENTIAL RISKS  
 
Monoclonal Antibody Specific Risks 
This study will be the second in which IXT-m200 will be given to humans; therefore, all specific risks of 
IXT-m200 are not known. Animal toxicology and human tissue cross reactivity data suggest that the risk 
of clinically significant side effects or toxicity in humans should be low.4 Given that there are more than 
50 Food and Drug Administration (FDA)-approved mAb medications, and several with non-endogenous 
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trials, risks may be predicted and strategies developed to mitigate these risks based on an understanding 
of the pharmacology of these approved medications.  
 
Reactions to mAb medications are categorized based on the timing of their occurrence in relation to 
administration of the medicine. Acute or infusion-related reactions may be defined as adverse 
pharmacologic events occurring in the first 24 hours following drug administration. Delayed reactions 
may occur from 24 hours to 14 days after administration, though they usually occur between 5 to 7 days 
after administration. 
 
Acute or infusion-related reactions may be either allergic, which are immunoglobulin E-mediated Type 1 
reactions, or non-allergic, which are mediated by release of proinflammatory cytokines. Both of these 
types of reactions can involve numerous organ systems, including the skin/cutaneous, cardiovascular, 
pulmonary, or GI (Table 3). Delayed reactions may present with rash and hives with pruritis, myalgias, 
and flu-like symptoms including arthralgias and stiffness, headaches, and fatigue.25-27 
 
Table 3. Infusion reaction signs and symptoms 
 
Other mAbs which are similar to IXT-m200 (eg, chimeric; rituximab - an anti-lymphoma mAb) or that 
target non-endogenous receptors or cell types (raxibacumab - an anti-Bacillus anthracis mAb; 
tefibazumab - an anti-Staphylococcus aureus mAb) may be used for predicting the prevalence of these 
possible risks.  
 
Infusion-related symptoms with other mAbs occur in between 10 and 40% of subjects. With tefibazumab 
for example, symptoms of headache, gastroesophageal reflux, and erythema were reported in 20% of the 
subjects and all but 1 were mild in severity. The moderately severe symptom, a headache, resolved with 
acetaminophen administration.28 Other infusion-related symptoms of mAbs include chills and/or fever 
(mild to moderate in severity) which are typically treated effectively with acetaminophen and 
diphenhydramine.28-30 Note that severe hypotension, bronchospasm, anaphylaxis, and death are reported 
with other mAbs that target endogenous cellular or tumor-related sites. Because IXT-m200 should neither 
bind complement nor endogenous cellular sites, the risks of these catastrophic events should be very low. 
 
Later developing signs and symptoms of mAb administration include nausea, vomiting, pain at the 
administration site, rigors, headache, dizziness, dyspnea, hypotension, elevated blood pressure, rash, and 
asthenia. These symptoms are reported to occur infrequently.28,30 
 
IXT-m200 Specific Risks 
During the Phase 1a study of IXT-m200, there were no SAEs or discontinuations due to 
treatment-emergent AEs. Overall, 90% of subjects experienced at least 1 AE, but there were no apparent 
trends in the frequence, relatedness, or severity of AEs with increased dose or between active- and 
placebo-treated subjects.5  
Organ system 
Signs/symptoms 
Skin/cutaneous 
Flushing, erythema, swelling of mucus membranes, pruritus, hives, angioedema, 
maculopapular rash, oropharyngeal or laryngeal edema 
Cardiovascular 
Tachycardia, hypotension, arrhythmia, chest pain, ischemia or infarction, cardiac 
arrest 
Pulmonary 
Nasal congestion, rhinitis, sneezing, bronchospasm, tachypnea, cyanosis, respiratory 
arrest 
Gastrointestinal 
Nausea, vomiting, diarrhea, gastroesophageal reflux 
Neurological 
Headache, syncopy, dizziness, feeling of impending doom 
Systemic 
Chills, fever, rigors, asthenia 

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Only 1 AE was definitely attributed to IXT-m200. A single subject experienced a CTCAE v.4.0 Grade 3 
infusion reaction half-way through the IXT-m200 infusion. The subject experienced a brief period of 
bronchospasm, in which the subject and PI heard a single expiratory wheeze. The infusion was stopped 
and the subject was treated with solu-medrol and diphenhydramine. No further symptoms were noted. 
The subject required outpatient therapy later for bronchitis. 
 
The most frequently reported AEs were increased blood creatine phosphokinase (CPK), upper respiratory 
tract infection, decreased hemoglobin, headache, increased aspartate aminotransferase (AST) and alanine 
aminotransferase, proteinuria, decreased white blood cell (WBC) count, and nasal congestion.  
 
Because the IXT-m200 is a mouse-human chimeric antibody, the potential for a human anti-chimeric 
antibody (HACA) response exists. Following single doses of IXT-m200, only 4 of 32 subjects were 
confirmed positive for HACA in the Phase 1a study.5 The development of HACA did not appear to be 
dose-related. 
 
METH Specific Risks 
METH can produce numerous side effects, some of which may be dangerous, including restlessness, 
dizziness, tremor, increased talkativeness, tenseness, irritability, weakness, insomnia, confusion, and 
hallucinations. Short-term adverse effects can include increased heart rate, paranoia resembling 
schizophrenia, hallucinations, aggressive behavior, insomnia, dysesthesias, panic, anxiety, and 
depression. Some individuals, particularly those who have used high doses of METH, have experienced 
severe paranoia and hallucinations. METH can produce the sensation of bugs crawling under or on the 
skin. Headache, a sensation of chilliness, or a sensation of flushing can also occur. Nausea, vomiting, 
diarrhea, severely decreased appetite, and abdominal cramps can occur as well. Unpleasant mental 
effects, such as depressed mood and anxiety, may develop at the end of the experiment as the effects of 
METH wear off. Fatigue and depression often follow METH use.  
 
These effects are rare at the doses and frequencies used in this protocol. However, occasionally extremely 
sensitive individuals may have some of these effects at lower, less frequent doses. We do not plan to use 
doses of METH that will produce these symptoms, and our patient recruitment approach should be able to 
exclude patients who are susceptible to these effects, but since not all the effects of METH are well 
understood and people’s sensitivity to the drug may vary, some of these symptoms may appear.  
Additionally, subjects that do not tolerate METH administration on Day 1 of this study will not be 
randomized to treatment and thus not administered additional METH challenges. Physiological signs will 
be monitored during drug infusion as described above. A physician will be present during drug 
administration and readily available for the remainder of the inpatient stay.  
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
IXT-m200 is an investigational product and may convey no benefit to patients. Based on nonclinical 
studies in rodents, it is believed that the product has the potential to prevent or reduce the reinforcing 
properties of METH, or the ‘high’. Further, high doses of IXT-m200 may lessen the effects of METH 
doses on blood pressure. Single doses of IXT-m200, as planned for this study, are not likely to have any 
long-term benefit. 
 

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3 
OBJECTIVES AND PURPOSE 
 
Primary Objective: To determine the effect of IXT-m200 on METH PK parameters relative to placebo. 
 
Secondary Objectives: To determine the effect of IXT-m200 on METH subjective effects, and to evaluate 
the safety and tolerability and PK of single, IV doses of IXT-m200 relative to placebo followed by 
weekly IV METH challenges in subjects with METH use disorders. 
 
4 
STUDY DESIGN AND ENDPOINTS 
 
4.1 
DESCRIPTION OF THE STUDY DESIGN 
 
A dose run-up approach to random-block dose assignment will be used (Table 4).  Approximately 126 
subjects will be enrolled into the study in 4 cohorts in order to have 42 subjects complete the study. 
Subjects will be counted as completers if they receive the third METH challenge following the IXT-m200 
dose and stay through the collection of the final METH PK sample 72 hours later (Day 22). Target 
numbers for completion are N = 10, 18, and 14 in the 6, 20, and 0 (placebo) mg/kg IXT-m200 treatment 
groups, respectively. The odds of placebo treatment is set at 33% across all 4 cohorts; the odds of high 
dose IXT-m200 (20 mg/kg) increases across successive cohorts. Subsequent cohorts will be enrolled 
1 week after all subjects of the previous cohort complete Day 49 of the study, pending safety analysis.  
 
Table 4. Staged cohort, dose run-up study design 
Cohort Dose Assignment 
1 
(N=18) 
Randomization 2:1 (odds of placebo = 33%) 
6 mg/kg IXT-m200 (n=12) 
Placebo (n=6) 
2 
(N=18) 
Randomization 1:1:1 (odds of placebo = 33%) 
6 mg/kg IXT-m200 (n=6) 
20 mg/kg IXT-m200 (n=6) 
Placebo (n=6) 
3 
(N=36) 
Randomization 2:1 (odds of placebo = 33%) 
 
20 mg/kg IXT-m200 (n=24) 
Placebo (n=12) 
4 
(N=54) 
Randomization 2:1 (odds of placebo = 33%) 
20 mg/kg IXT-m200 (n=36) 
Placebo (n=18) 
 
Each cohort will participate in a standard, double-blind assessment of METH challenges requiring a 
23-day/22-night inpatient study followed by an extended follow-up period. During the 23-day stay 
(Days -1 to Day 22), subjects will receive METH challenges before and after administration of IXT-m200 
or placebo. On Day 1, subjects will receive a METH challenge (placebo [saline] and 30 mg METH, 
4 hours apart, in random order, given under double-blind conditions). Those subjects who tolerate the 
METH doses as measured by AEs and cardiovascular parameters, and who also provide appropriate 
subjective responses will be randomized to treatment; those who do not will be discharged on Day 3. On 
Day 4, IXT-m200 (6 or 20 mg/kg) or placebo will be administered in a double-blind manner. METH 
challenges will be repeated weekly for 3 weeks (Days 5, 12, and 19) to evaluate the enduring effects of 

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METH following IXT-m200 or placebo administration. Subjects may be discharged on Day 22 or given 
the option to continue into the Inpatient Extension Stay. 
 
Subjects who successfully complete through Day 22 may remain in the study and continue into an 
optional Inpatient Extension Stay for an additional 7 days duration. On Day 26, subjects will receive the 
METH challenge dose regimen (placebo and 30 mg METH, 4 hours apart in random order). On Day 29, 
subjects will be discharged from the the clinic and will participate in an extended follow-up period.   
 
Because of the expected long half-life of IXT-m200, the study will continue to monitor the safety of all 
study subjects in an outpatient manner through Day 126. Outpatient follow-up visits will occur weekly for 
several weeks and then every 3 weeks.  
 
4.1.1 PRIMARY ENDPOINT 
 
 
Change in plasma METH AUC or Cmax resulting from METH challenge doses following single IV 
doses of IXT-m200. 
 
4.1.2 SECONDARY ENDPOINTS 
 
 
Change in subjective effects of METH challenge doses as measured by DEQ (ie, reduction of ‘High’ 
or ‘Liking’). 
 
Safety and tolerability of IXT-m200 followed by METH challenges as measured by physical 
examinations and vital sign, AE, ECG, and clinical laboratory testing, and immune response by 
measurement of anti-IXT-m200 antibody levels. 
 
Pharmacokinetics of IXT-m200 following single administration. 
 
5 
STUDY ENROLLMENT AND WITHDRAWAL 
 
5.1 
PARTICIPANT INCLUSION CRITERIA 
 
Subjects meeting the following criteria will be considered for inclusion in the study: 
 
1. Subject voluntarily agrees to participate in this study and signs an IRB-approved informed consent 
form prior to performing any of the screening procedures.  
2. Subjects must be able to verbalize understanding of the consent forms, provide written informed 
consent, and verbalize willingness to complete study procedures. 
3. Males or females between 21 to 50 years of age, inclusive. 
a. Female subjects should be of nonchildbearing potential or, they should be nonpregnant, 
nonlactating, and agree to use medically acceptable forms of birth control (oral contraceptive 
pills; contraceptive patches; vaginal ring; diaphragm, sponge, or condom with spermicide; 
hormone injection; or intrauterine device) from screening to end-of-study follow-up, or have a 
partner who has had a vasectomy. 
b. Male subjects need to have had a vasectomy or agree to use a condom and spermicide in addition 
to their female partners using a form of birth control. They should agree not to donate sperm for 
90 days post IXT-m200 dose. 
4. Body mass index (BMI) between 18.0 and 35.0 kg/m2, inclusive, at screening or check-in. Body 
weight ≥ 50 kg and ≤ 100 kg at screening or check-in. 
5. Subjects have hematology and chemistry laboratory tests that are within normal (+/- 10%) limits with 
the following exceptions: a) liver function tests (total bilirubin, ALT, AST, and alkaline phosphatase) 

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< 3 times the upper limit of normal, and b) kidney function tests (creatinine and BUN) < 2 times the 
upper limit of normal. 
 
In addition, potential subjects must meet the following METH use criteria: 
 
6. Subjects meet DSM-5 criteria for METH use disorder and are not seeking treatment at the time of the 
study. 
7. Subjects will be experienced METH users with a history of non-therapeutic METH use for 2 or more 
years. Subjects must have experience with smoking or IV injection of METH. 
8. Current METH use (past 30 days) less than daily, self-reported and documented by calendar-based 
timeline follow-back.  
9. Primary current (past 30 days) route of METH SA other than IV (ie, smoking, snorting, or oral).  
10. Subjects agree not to take METH from any source outside of the study during their participation in 
the study. Subjects agree not to take substances that are structurally similar to METH (eg, 
amphetamine or 3,4-Methylenedioxymethamphetamine [MDMA]). 
11. Subjects must provide a negative urine toxicology sample prior to admission to the unit on Day -1 for 
the study.   
 
5.2 
PARTICIPANT EXCLUSION CRITERIA 
 
Subjects presenting with any of the following will not be included in the study: 
 
1. A history of treatment with a monoclonal antibody (mAb) in the past year. 
2. Known or suspected allergy sensitivity to IXT-m200 based on known allergies to other mAbs, or 
which suggests an increased potential for an adverse hypersensitivity to IXT-m200. 
3. History of severe allergy (rash, hives, breathing difficulty, etc) to any medications, either prescription 
or non-prescription, including dietary supplements or herbal medications. 
4. History of allergic or environmental bronchial asthma. 
5. Clinically significant history of or current abnormality or disease of any organ system, including 
renal, hepatic, GI, cardiovascular, pulmonary (including chronic asthma), endocrine (eg, diabetes), 
central nervous, or hematologic systems, or recent clinically significant surgery. 
6. Current diagnosis or history of major psychiatric illness in the past two years (eg, affective disorders, 
schizophrenia, bipolar disorder, major depression, or other psychiatric condition that requires 
medication) or other current psychiatric condition requiring medication that in the opinion of the 
Investigator precludes study participation, other than methamphetamine dependence. 
7. Considered by the PI to be at imminent risk of suicide or injury to self, others, or property, or the 
subject has attempted suicide within the past year prior to Screening. Past year (12 months) history of, 
or current evidence for, suicidal ideation or those who were actively suicidal based on the Columbia-
Suicide Severity Rating Scale (C-SSRS). 
8. Current dependence on alcohol according to DSM-5 criteria, or heavy use defined as >28 alcoholic 
drinks per week if male and >21 drinks per week if female in last 30 days (1 alcoholic drink is 
defined as 12 oz. beer, 4 oz. wine, or 1 oz. distilled spirits). 
9. Current dependence on other drugs according to DSM-5 criteria, except amphetamines, or marijuana 
and nicotine used in moderate amounts (ie, ≤4 cigars or pipes of tobacco per day or ≤30 cigarettes or 
equivalents per day in last 30 days). Subjects will be allowed to smoke (nicotine only) during the 
inpatient stay, except from 1 hr before dosing of either METH or IXT-m200 until 2 hr after dosing is 
complete. 
10. History of seizure, epilepsy, severe head injury with residual neurologic effects, multiple sclerosis, or 
stroke. 

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11. Abnormal pre-admission vital signs, physical examination, clinical laboratory, ECG, or any safety 
variable which is considered clinically significant for this population by the PI or Sponsor (or 
designee).  
a. Abnormal ECG parameters include, but are not limited to ventricular hypertrophy, left axis 
deviation, atrial or ventricular arrhythmias other than sinus, and prolonged QTc (greater than 
500 ms).  
b. Volunteers who have or are suspected to have Gilbert’s syndrome will be discussed on a case 
by case basis by the PI, Medical Monitor, and Sponsor. 
12. History of stable or unstable cardiovascular disease. 
13. Treatment with any prescription medications or over the counter nutritional supplements within 14 
days prior to the first dose of study medication.  
14. Ingestion of any approved prescription anti-obesity drug or taken any over-the-counter medication for 
weight loss within a period of 90 days prior to the first dose of study medication. 
15. Ingestion or use of any investigational medication or device within 30 days prior to the first dose of 
study medication. 
16. Acute illness within 5 days prior to the first dose of study medication, eg, flu syndrome, GI virus, or 
clinically significant indigestion (eg, reflux). 
17. Positive result for hepatitis B surface antigen (HBsAG), hepatitis C (HepC) antibody, hepatitis A 
immunoglobulin M (IgM), or HIV Viral Serology, or nucleic acid testing (NAT) tests at screening. 
18. Positive breath alcohol test or positive urine drug test for illicit substances (barbiturates, 
benzodiazepines, cocaine, opiates, phencyclidine, propoxyphene, MDMA, METH, or amphetamine) 
on Day -1 (a positive test for tetrahydrocannabinol [THC] may be acceptable if the subject is not 
intoxicated at the discretion of the Investigator). 
19. Subjects with history of donated blood, plasma or platelets in last 30 days, and who do not agree to 
refrain from blood, plasma, platelets, egg or sperm donation during the study period.  
20. Predominant or only route of METH SA is IV.  
21. Any subject judged by the PI or Sponsor (or designee) to be inappropriate for the study. 
 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
A broad spectrum of recruitment methods will be employed, and best practices integrated, to ensure all 
possible subjects are considered. Database mining, along with Community Outreach, Radio 
Advertisements, Print and Social Media as needed to increase awareness, will be employed. The clinical 
site’s call center is comprised of trained scheduling and subject/patient recruitment specialists who 
pre-screen all incoming calls prior to scheduling their pre-screening visits and can handle large volumes 
of incoming calls. Dedicated recruiters confirm all study visits within 24 hours of the appointment as well 
as contacting all no-shows or cancelled appointments. Taxi, ride-share, or other transportation service 
may be utilized to drive participants to and from their appointments in order to enhance subject 
participation and reduce attrition.  
 
The advertising process, if necessary, would begin with an evaluation of the target population, 
demographics, media costs, and previous recruitment plan results. The clinical site recruitment team has 
extensive knowledge regarding all advertising mediums in the local market and surrounding areas. 
 

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5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION 
 
5.4.1 REASONS FOR WITHDRAWAL OR TERMINATION 
 
Subjects may be withdrawn from the study at any time for reasons including the following: 
 
 
at their own request or at the request of their legally authorized representative, 
 
if a subject indicates a desire for treatment of their METH use, 
 
the subject meets an exclusion criteria (either newly developed or not previously recognized) that 
precludes further study participation, 
 
any clinical AE, laboratory abnormality, or other medical condition or situation occurs such that 
continued participation in the study would not be in the best interest of the subject, 
 
if, in the PI’s opinion, continuation in the study would be detrimental to the subject’s well-being, or 
 
at the specific request of InterveXion (Sponsor) or clinical site. 
 
5.4.2 HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION 
 
In all cases, the reason for withdrawal must be recorded in the electronic Case Report Form (eCRF) and 
in the subject’s medical records. If the reason is not known, an attempt must be made to follow up with 
the subject to establish whether the reason was an AE, and, if so, this must be reported in accordance with 
the procedures in Section 8.4.1.   
 
If, at any point in their participation in the study, a subject indicates a desire for treatment of their METH 
use, no more METH challenges will be given to the subject and he/she will be referred for treatment. 
Subjects who begin treatment for their METH use during the study will complete all follow-up safety 
evaluations. 
 
As far as possible, all examinations scheduled for the end-of-study evaluations must be performed on all 
subjects who participate but do not complete the study according to protocol. Subjects will be followed 
for 126 days. Dropouts may be replaced at the discretion of the PI in conjunction with the Sponsor. The 
PI will make every effort to contact subjects lost to follow-up and document results.  
  
Subjects who have an ongoing AE at the time of study completion will be followed up until the event 
resolves, the Sponsor and the PI agree that further follow-up is not medically necessary, or until the 
subject is lost to follow-up.  
 
5.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to the PI, IRB, NIDA, Sponsor, and FDA.  
 
Circumstances that may warrant termination or suspension include, but are not limited to:  
 
 
Determination of unexpected, significant, or unacceptable risk to participants  
 
Insufficient compliance to protocol requirements  
 
Data that are not sufficiently complete and/or evaluable  
 
Determination of futility  
 

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The study may resume once any concerns about safety, protocol compliance, and data quality are 
addressed and satisfy the Sponsor, IRB, and/or FDA. 
 
6 
STUDY AGENT 
 
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION 
 
6.1.1 ACQUISITION 
 
Study Agent: Sponsor will provide the required number of vials of IXT-m200. The Investigator will be 
responsible for acquiring commercially available normal saline for dilution of IXT-m200 into its final 
dose formulation. 
 
Challenge Agent: METH will be requested from the NIDA Drug Supply Program and supplied to the 
study site(s) upon receipt of the appropriate DEA request forms. 
 
Placebo: The Investigator will be responsible for acquiring commercially available normal saline for use 
as placebo for IXT-m200 and METH. 
 
6.1.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
 
Study Agent: IXT-m200 is formulated as an injection solution containing approximately 20 mg/mL 
IXT-m200 in 10 mM sodium phosphate, pH 6.5, 150 mM sodium chloride, and 0.05% w/v 
polysorbate 80. The product is a clear solution packaged in 10 mL glass vials with flurotec stoppers and 
flip-off seals. Labels will be similar to the following: 
 
InterveXion Therapeutics® 
Anti-methamphetamine IXT-m200 
18.5-21.5 mg/mL 
Manufactured: 24 Oct 2017 
UIP Lot: 073I1017 
Catalent Lot: 17032 
10 mM sodium phosphate, 150 mM sodium chloride, pH 6.5, with 0.05% Tween 80 
Store refrigerated at 2 to 8°C 
CAUTION: New Drug – Limited by Federal (or United States) law to investigational use only. 
InterveXion Therapeutics, LLC 
4301 W. Markham, Slot 831, Little Rock, AR 72205 
 
Challenge Agent: METH is formulated for human use as an injection solution containing approximately 
10 mg/mL METH in 120 mM sodium acetate, pH 4.5, and 1% (10 mg/mL) benzyl alcohol. The product is 
a clear solution packaged in glass vials. The labeling should include the words ‘Methamphetamine HCl 
Injection’. 
 
Placebo: Normal saline (0.9% sodium chloride) should be a clear solution for injection. Packaging and 
labeling will be appropriate for use. 
 
 
 

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6.1.3 PRODUCT STORAGE AND STABILITY 
 
Study Agent: IXT-m200 vials are single-use and should be stored refrigerated at 2 to 8°C. The stability of 
the product is still under investigation and stability protocols will run concurrent to the study. A previous 
lot of IXT-m200 remained stable after 48 months of refrigerated storage when the stability protocol was 
terminated. 
 
Challenge Agent: METH must be stored in a safe, secure area with limited, controlled access in 
accordance with all local, state, and federal regulations for Schedule II controlled substances. METH vials 
should be stored at controlled room temperature with protection from light. Stability is typically 2 years 
from date of manufacture and will be indicated on the Certificate of Analysis (or equivalent) when 
received. 
 
Placebo: Normal saline should be stored per the manufacturer’s recommendations. 
 
6.1.4 PREPARATION 
 
Study Agent: The appropriate amount of IXT-m200 should be diluted into a bag of normal saline so that 
the total volume is 225 mL prior to dosing; mix by gentle inversion.  Rounding to 2 decimal places will 
be used for drug volume calculations. Doses are stable for 8 hours at room temperature. 
 
Challenge Agent: METH should be dosed undiluted. 
 
Placebo: Normal saline requires no preparation prior to administration. 
 
6.1.5 DOSING AND ADMINISTRATION 
 
Study Agent and Placebo: Subjects in each cohort will be randomized to treatment or placebo on Day 2 or 
3. On Day 4, a light meal or snack containing minimal unrefined sugar and caffeine will be provided 
1 to 2 hours prior to dosing. Subjects should lie supine or semi-reclined during dose administration and 
remain in such position for 2 hours following dosing, except during ECG measurements. Subjects should 
refrain from strenous activity from 72 hours prior to dosing through 48 hours afterward. Fluids will be 
restricted from 1 hour predose to 2 hours post start of infusion and then allowed ad libitum. A 
standardized lunch will be provided approximately 4 hours after the beginning of the infusion. 
 
The IXT-m200 infusion start/stop time, infusion rate, infusion volume, cumulative volume at each rate 
change, whether the infusion was completed, if it was stopped, or stopped and restarted will be recorded 
in the eCRF. 
 
Challenge Agent and Placebo: Subjects will receive METH (30 mg) and placebo on each challenge day in 
randomized order, 4 hours apart. The first dose should be administered in the morning, approximately 
1 hour after a light meal or snack containing minimal unrefined sugar and caffeine, with the subject semi-
reclined. The second dose should be administered similarly, 4 hours after the first dose. A light meal or 
snack containing minimal unrefined sugar and caffeine will be offered 3 hours after the morning dose, 1 
hour before the afternoon dose. Fluids are not restricted but should be kept to moderate levels during 
METH challenge days. 
 
 

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6.1.6 ROUTE OF ADMINISTRATION 
 
Study Agent and Placebo: IXT-m200 and normal saline will be administered by IV infusion using an 
infusion pump over 2 hours using the progressively increasing rates of infusion described in Table 5. A 
50 mL saline flush should be dispensed after each dose to ensure the entire dose is flushed through the 
infusion set. 
 
Table 5. Infusion rate progression 
Time increment 
(min) 
Administration 
rate (mL/hr) 
Incremental 
volume (mL) 
Total volume 
(mL) 
0-15 
10 
2.5 
2.5 
15-30 
20 
5 
7.5 
30-45 
40 
10 
17.5 
45-60 
80 
20 
37.5 
60-90 
150 
75 
112.5 
90-120 
225 
112.5 
225 
 
Challenge Agent and Placebo: METH and normal saline will be administered IV. Each dose will be 
administered by hand over 2 minutes with an observer providing time reminders during the dose. 
 
6.1.7 STARTING DOSE AND DOSE ESCALATION SCHEDULE 
 
In order to monitor the safety and tolerability of IXT-m200 in the METH users, a dose run-up approach to 
random-block dose assignment will be used so that the lower IXT-m200 dose (6 mg/kg) will be evaluated 
in a staged cohort of subjects before the higher dose (20 mg/kg) is evaluated (Section 4.1). In conjunction 
with safety monitoring, this design assures the opportunity to observe early safety findings in at least 12 
subjects in the low IXT-m200 dose condition before any subjects are exposed to the high dose condition. 
Subsequent cohorts will be enrolled 1 week after all members of the previous cohort complete Day 49 of 
the study, pending safety analysis.  
 
6.1.8 DOSE ADJUSTMENTS/MODIFICATIONS/DELAYS 
 
Study Agent: Subjects will only be randomized and dosed with IXT-m200 if they received and tolerated 
the METH challenge regimen on Day 1. Additionally, subjects must have responded to the drug effects 
questionnaire as appropriate to the METH dose administered. 
 
Each subject will receive only a single dose of IXT-m200, therefore no dose adjustment or modification 
will be done after the infusion is completed. If however, there is an infusion reaction, the dose should be 
stopped and the subject treated following Section 7.7. 
 
Dose Limiting Toxicity (DLT): An AE (Section 8) will be considered clinically significant if it results in 
significant impairment of the subject's ability to carry out usual activities or if the AE presents a 
significant hazard to the subject. Any such AE or SAE will be considered a DLT if it is Grade 3 (see 
section 8.2.1 for grading scale) unless the event was clearly unrelated to IXT-m200 administration 
(Section 8.2.2 for definitions and examples). Additionally, all Grade 2 or higher toxicities will be 
reviewed by the Sponsor, PI, and Medical Monitor for possible classification as a DLT, as defined above. 
 
Challenge Agent: METH dosing will be stopped or not repeated if subjects exhibit vital sign responses 
out of accepted ranges, or if they exhibit CNS symptoms of paranoia or hallucinations.  
 

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6.1.9 DURATION OF THERAPY 
 
Subjects will receive only a single dose of IXT-m200.  
 
6.1.10 TRACKING OF DOSE 
 
All study treatments will be administered in a blinded manner by the PI or designee.   
 
6.2 
STUDY AGENT ACCOUNTABILITY PROCEDURES 
 
Study Agent: All required IXT-m200 vials will be shipped to the study sites prior to study initiation.  
All unused supplies will be checked against the drug accountability records during the study and/or at the 
end of the study. All unused study drug must be disposed of in accordance with applicable requirements.  
 
Challenge Agent: METH vials will be shipped to the study sites prior to study initiation with additional 
vials requested as necessary. Any unused drug will be disposed of according to standard practices. 
 
7 
STUDY PROCEDURES AND SCHEDULE 
 
7.1 
STUDY PROCEDURES/EVALUATIONS 
 
7.1.1 STUDY SPECIFIC PROCEDURES  
 
Medical and Medication Histories 
 
Medical history: A complete medical history will be obtained at screening by interview and any 
available medical records. Interim medical histories will be obtained at all subsequent time points. 
 
Medication history: A complete medication history will be obtained by interview and any available 
medical records, with particular attention to any medications taken in the previous 12 months. 
Assessment of eligibility should include a review of permitted and prohibited medications.  
 
Physical Examination, Vital Sign Measurement, Height and Weight 
 
A complete physical examination (excluding rectal/genital and breast examination) will be performed 
at screening. The physical examination will consist of vital signs and an examination of the 
following: general appearance, neurological, skin, head, eyes, ears, nose, throat, neck, lymph nodes, 
chest, heart, abdomen, and extremities.  
o Subsequent exams will be brief (heart, lungs, abdomen, skin, weight, and vital signs), or targeted 
if AEs or other complaints will require appropriate and more detailed exams. 
 
Vital sign measurements (heart rate, blood pressures [systolic and diastolic], respiratory rate, 
temperature [oral], and pulse oximetry readings) will be obtained, after the subject has been resting 
supine for at least 5 minutes, every 0.25 hours during IXT-m200 dosing, then 0.25, 0.5, 1, 2, and 4 
hours (± 5 min) after dosing is completed, and as needed afterward until normalization. On Days 1, 5, 
12, 19, and 26 (if applicable), vital signs will be measured within 30 min prior to the first dose, then 
0.25, 1, 2, 4, 4.25, 5, 6, and 8 hours (± 5 min) relative to the first METH challenge dose. 
Measurements will be done at least daily during the inpatient stay and at each follow-up visit. Each 
test may be repeated once at each time point if the initial result is out of range. 
 
Height and weight will be obtained during screening, and weight will be obtained on Study Day -1 
and all follow-up visits. 
 

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Psychiatric Evaluation 
Columbia-Suicide Severity Rating Scale: Suicide-related thoughts and behaviors will be assessed 
using the C-SSRS. Regulatory agencies have been interested in examining suicide-related thoughts 
and behaviors in patients receiving antidepressant and other drugs used in psychiatric illnesses. In 
August 2012, the FDA’s Division of Psychiatry Products communicated that information regarding 
suicide-related thoughts and behaviors should be prospectively collected in a standardized format 
(Columbia Classification Algorithm or Suicide Assessment) from all clinical studies, including 
Phase 1 studies for all drugs in development to enable the analysis of suicide-related thoughts and 
behaviors in an aggregated fashion. The tool was developed by a National Institute of Mental Health 
trial group for the purpose of being a counterpart to the FDA’s categorization of suicidal events. 
 
The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and 
behaviors during the assessment period. The scale includes suggested questions to solicit the type of 
information needed to determine if a suicide-related thought or behavior occurred. The C-SSRS will 
be administered by appropriately trained site personnel. A referral to a psychiatrist will be made to in 
the event of a significant finding on the C-SSRS, i.e., active suicidal ideation with some intent to act, 
without specific plan, or active suicidal ideation with specific plan or intent in the past 12 months. 
 
All AEs obtained through the questionnaire will be recorded. The Sponsor or its designee will be 
alerted within 24 hours of the PI’s awareness of any SAEs from these questionnaires.  
 
The C-SSRS may be administered at any time to a subject who indicates, or is suspected to have, new 
suicidal intentions during the study. 
 
Electrocardiogram and Telemetry 
 
Electrocardiogram (12-lead) will be recorded as outlined in the Schedule of Events (Section 7.3.6; 
with a window of ± 10 min relative to the nominal time point) after the subjects have been supine for 
5 min. Standard ECG parameters including heart rate (HR), QRS, PR, QT, and QTc intervals will be 
measured. The ECGs will be read by a study physician to assess for any abnormalities. Abnormal 
ECG parameters include, but are not limited to ventricular hypertrophy, left axis deviation, atrial or 
ventricular arrhythmias other than sinus, and prolonged QTc (greater than 500 ms). ECGs may be 
repeated if data quality is compromised due to poor lead placement or machine error. 
 
Telemetry monitoring will be continuous from 0.5 hours before dosing to 8 hours post dose and until 
normal: defined as heart rate within 20% of baseline at the final time point. Telemetry will be 
monitored as it is recorded, and a physician will review the data after completion of the recording. 
 
Biological Specimen and Laboratory Evaluations 
 
Blood will be taken for clinical laboratory evaluations (Section 7.2.1). 
 
Blood will be taken for analysis of IXT-m200, detection of anti-IXT-m200 antibodies, or analysis of 
METH and its metabolite amphetamine (AMP) (Section 7.2.2). Samples will be processed according 
to guidelines in the study laboratory manual. 
 
Urine samples will be taken for drug tests and urinalysis. 
 
Urine will be collected for analysis of METH and AMP elimination time course (Section 7.2.2). 
Samples will be processed according to guidelines in the study laboratory manual. 
 
Estimated amounts of blood volumes necessary are summarized in Table 6. 
 

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Table 6. Estimated blood volume to be collected from each subject 
Reason 
Volume per 
sample (mL) 
Number of 
samples 
Total volume 
(mL) 
Screening serology 
8.5 
1 
8.5 
Clinical labs (7.2.1; not including cytokines) 
15.2 
15 
228 
Cytokines (samples 2 and 3 collected only if 
an infusion reaction occurs) 
27 
1 (3) 
27 (81) 
IXT-m200 PK  
5 
18 
90 
METH PK through Day 22 (Day 29) 
3 
68 (85) 
204 (255) 
HACA 
5 
4 
20 
 
Subjective Measures 
 
A DEQ will be administered using a mobile tablet and measured using 100-point visual analog scales 
anchored from “Not at all” to “Extremely”. Questions will include the following, or similar:  
o “Do you FEEL a drug effect right now?” 
o “Are you HIGH right now?” 
o “How GOOD are the drug effects you are feeling right now?” 
o “How STIMULATED do you feel right now?” 
o “Do you DISLIKE any of the effects you are feeling right now?” 
o “Do you LIKE any of the effects you are feeling right now?” 
o “Would you like MORE of the drug you took right now?” 
o “How much do you CRAVE the drug right now?” 
 
The questionnaire will be administered within 30 min prior to the first dose, then 15, 30, 45, 60, 90, 
120, and 180 minutes relative to each METH or placebo (PBO; for METH) dose. 
 
The DEQ administered at 180 minutes relative to each METH or PBO dose will also include the 
following two questions measured with a bipolar scale. 
o “Would you TAKE this DRUG AGAIN?”  
o “What is your OVERALL DRUG LIKING?” 
 
Appropriate subjective responses on Day 1 are higher responses on the visual analog scales after the 
METH dose relative to the placebo dose for the drug liking questions (ie, FEEL, HIGH, 
STIMULATED). These responses should be an average of ≥11 points higher than the placebo 
responses in each subject. 
 
 
7.2 
LABORATORY PROCEDURES/EVALUATIONS 
 
7.2.1 CLINICAL LABORATORY EVALUATIONS  
 
Blood and urine samples for clinical laboratory safety assessments will be collected according to standard 
operating procedures (SOPs). All blood and urine specimens will be sent to a local reference laboratory 
for analysis and testing. Local lab reference ranges (current published version) will be used for evaluation 
of results, where values are not otherwised defined in this protocol, at the discretion of the investigator. 
The procedures for the collection, handling, and shipping of laboratory samples will be specified in the 
laboratory manual(s) provided to the study site. 
 
Baseline laboratory assessments will be performed on Day -1. Results of these assessments must be 
available and reviewed before dosing on Day 1. Abnormal screening or Day -1 for protocol-defined 
laboratory values are exclusionary. The subject may be retested to see if the value/parameter returns to a 
defined range only if there is a plausible alternative explanation for the out-of-range value. One repeat test 
is permitted to confirm a plausible explanation for an abnormal value.  
 

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Drug and Alcohol  
 
Qualitative urine drug (amphetamines, MDMA, barbiturates, benzodiazepines, cocaine, opiates, THC, 
phencyclidine, and propoxyphene) and alcohol breath tests will be performed at screening, upon 
check-in on Day -1, and at each outpatient follow-up visit. 
 
Hematology 
 
Erythrocytes: red blood cell (RBC) count, hematocrit, hemoglobin, mean corpuscular hemoglobin, 
mean corpuscular hemoglobin concentration, mean corpuscular volume, red cell distribution width, 
and reticulocyte count as an absolute value. 
 
Leukocytes: WBC and differential (basophils, eosinophils, lymphocytes, monocytes, and neutrophils) 
reported as absolute values. 
 
Coagulation: platelet count, prothrombin time measured as international normalized ratio, activated 
partial thromboplastin time. 
 
Serum Chemistry 
 
Liver: alkaline phosphatase, ALT, AST (serum glutamic-oxaloacetic transaminase), bilirubin (total, 
direct, and indirect), gamma-glutamyl transferase, and lactic dehydrogenase. 
 
Renal: blood urea nitrogen, creatinine, and uric acid. 
 
Electrolytes, sodium, potassium, chloride, and carbon dioxide. 
 
General: CPK, albumin, calcium, magnesium, glucose (fasting), phosphate, protein (total), amylase, 
and lipase. 
 
Specific: Troponin 1 (only on Days 2, 6, 13, and 20) and prostate specific antigen (PSA; tested only 
on Days -1, 20, and 126). 
 
Urinalysis 
 
Microscopic: pH, specific gravity, glucose, ketones, leukocyte esterase, nitrites, occult blood, and 
protein, RBCs/hpf, WBCs/hpf, bacteria, casts, epithelial cells, mucous threads, and crystals. 
 
Quantitative: protein and creatinine if microscopic is positive for protein. 
 
Serum Pregnancy Test 
 
Serum human chorionic gonadotropin test will be performed on all females who have not had a 
hysterectomy at screening, on Day -1, and approximately monthly at follow-up Days 28, 56, 84, and 
126; follicle-stimulating hormone tests will be performed in female subjects of nonchildbearing 
potential at screening. 
 
Serology (Screening only) 
 
Hepatitis B surface antigen (HBsAG), hepatitis C (HepC) antibody, hepatitis A immunoglobulin M 
(IgM), or HIV Viral Serology, or nucleic acid testing (NAT) tests will be performed at screening. 
 
Cytokine analysis (Day 4 only) 
 
Cytokine IL-1B, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and TNFα levels will be determined only 
if any IXT-m200 infusion reaction occurs. Samples should be taken on Day 4 at pre-dose for all 
subjects, then at 1 and 4 hr after the start of any infusion reaction, if necessary. 
 
7.2.2 OTHER ASSAYS OR PROCEDURES 
 
 
Serum PK of IXT-m200: A validated enzyme linked immunosorbent assay (ELISA) procedure will 
be used to quantitate IXT-m200 in serum samples taken at specified time points (Section 7.3.6) after 
dosing. Approximately 1 mL per sample is required. 

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 
Plasma PK of METH and AMP: A validated liquid chromatography-mass spectrometry procedure 
will be used to quantitate METH and AMP in plasma samples taken at specified time points (Section 
7.3.6) after dosing. Approximately 1 mL per sample is required. 
 
Urine PK of METH and AMP: A validated liquid chromatography-mass spectrometry procedure will 
be used to quantitate METH and AMP in urine samples taken at specified time points (Section 7.3.6) 
after dosing. Approximately 1 mL per sample is required. 
 
Immunogenicity of IXT-m200: A validated electrochemiluminescent procedure will be used to 
quantitate HACA in serum samples taken at specified time points (Section 7.3.6) after dosing. 
Approximately 1 mL per sample is required. 
 
7.2.3 SPECIMEN PREPARATION, HANDLING, AND STORAGE 
 
Serum, plasma, and urine samples for PK and immunogenicity analysis will be processed, handled and 
stored according to guidelines in the study laboratory manual. 
 
7.2.4 SPECIMEN SHIPMENT 
 
Specimen shipments will be handled according to guidelines in the study laboratory manual. 
 
7.3 
STUDY SCHEDULE 
7.3.1 SCREENING 
 
Screening Visit (Within 30 Days Prior to Enrollment) 
 
Subjects will sign the study-specific informed consent form (ICF) prior to any study-specific 
screening procedures being performed. The signed ICFs will be retained and archived and another 
copy will be provided to the subject  
 
Procedures and assessments at screening will consist of the following to determine eligibility based 
on inclusion/exclusion criteria:  
o Obtain demographic data 
o Review medical history 
o Review medications history  
o Perform medical examinations (physical examination, vital signs, clinical laboratory, urine drug 
and alcohol breath tests, and ECG assessments)  
o Assess use of METH and other illicit drugs for the past 30 days  
o Diagnose Substance Use Disorder(s) using DSM-5 criteria 
o Administer C-SSRS (lifetime history version) 
o Collect blood for HBsAg, HepC antibody, hepatitis A IgM, and HIV antibody (or nucleic acid) 
tests 
 
Schedule study visits for participants who are eligible and available for the duration of the study 
 
7.3.2 ENROLLMENT/BASELINE 
 
Enrollment (Day -1) 
 
Review and verify informed consent of potential participant 
 
Verify inclusion/exclusion criteria 
 
Review and update medical history 
 
Record vital signs, results of physical examinations, and ECG assessment 
 
Administer standardized drug assessment of METH and other drug use since last visit 
 
Alcohol breath test 

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 
Collect blood/urine for urine drug screen and clinical laboratory assessments. Subjects with positive 
urine drug or alcohol tests (except for nicotine and marijuana) will not be enrolled, but may return at a 
later date if they still qualify 
 
Monitor telemetry for a minimum of 4 hr 
 
Admit to inpatient unit 
 
7.3.3 INPATIENT STAY, EXTENSION STAY, AND FOLLOW-UP  
 
Adverse events and vital signs will be recorded continuously throughout the inpatient stay and each 
follow-up visit.  At each time point where multiple assessments are to be done, the priority order of 
collection should be: PK > DEQ > Vital signs > ECG. 
 
Inpatient Stay (Day 1) 
 
Record vital signs and results of ECG assessment. If not within acceptable limits, do not administer 
METH challenge 
 
Start telemetry monitoring and record from 30 minutes prior to 8 hours after METH challenge dosing 
 
Administer METH challenge doses 4 hours apart 
 
Complete DEQ following METH challenge doses 
 
Collect blood and urine for METH PK 
o Continue collecting blood samples through the 72 hour time point 
o Continue collecting urine through 36 hours 
 
Inpatient Stay (Day 2) 
 
Record results of physical examination, clinical laboratory, and ECG assessments 
 
Inpatient Stay (Day 3) 
 
Randomize to IXT-m200 dose levels those subjects who 1) tolerated the METH challenge dose 
regimen as measured by AE and cardiovascular parameters, and 2) who also provided appropriate 
DEQ responses on Day 1. Discharge subjects who do not meet these criteria 
 
Collect blood for HACA 
 
Inpatient Stay (Day 4) 
 
Start telemetry monitoring and record from 30 minutes prior to 8 hours after IXT-m200 dosing 
 
Collect pre-dose cytokine sample. Collect samples at 1 and 4 hr after the start of any infusion 
reaction, if necessary. 
 
Administer IXT-m200 dose 
 
Collect blood for IXT-m200 PK 
o Continue collecting blood samples through 72 hours post start of the infusion 
 
Inpatient Stay (Days 5, 12, and 19) 
 
Collect blood for IXT-m200 PK prior to the first METH challenge dose 
 
Record vital signs and results of ECG assessment. If not within acceptable limits, do not administer 
METH challenge 
 
Start telemetry monitoring and record from 30 minutes prior to 8 hours after METH challenge dosing 
 
Administer METH challenge doses 4 hours apart 
 
Complete DEQ following METH challenge doses 
 
Collect blood and urine for METH PK 
o Continue collecting blood samples through the 72 hour time point 
o Continue collecting urine through 36 hours 

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Inpatient Stay (Days 6, 13, and 20) 
 
Record results of physical examination, clinical laboratory, and ECG assessments 
 
Inpatient Stay (Day 22) 
 
Schedule at least the next follow-up visit, more if subject agrees 
 
Record vital signs and results of physical examination 
 
Administer C-SSRS (since last assessment) if subject is to be discharged 
 
Discharge subjects if vital signs and physical exam are acceptable if subject is not participating in the 
Inpatient Extension Stay 
 
 
Inpatient Extension Stay (Day 26; Subjects who successfully complete through Day 22 may remain in the 
unit if they elect to continue the inpatient stay) 
 
Collect blood for IXT-m200 PK prior to the first METH challenge dose 
 
Record vital signs and results of ECG assessment. If not within acceptable limits, do not administer 
METH challenge 
 
Start telemetry monitoring and record from 30 minutes prior to 8 hours after METH challenge dosing 
 
Administer METH challenge doses 4 hours apart 
 
Complete DEQ following METH challenge doses 
 
Collect blood and urine for METH PK 
o Continue collecting blood samples through the 72 hour time point 
o Continue collecting urine through 36 hours 
 
Inpatient Extension Stay (Day 27) 
 
Record results of physical examination, clinical laboratory and ECG assessments 
 
Inpatient Extension Stay (Day 28) 
 
Collect blood for HACA 
 
Inpatient Extension Stay (Day 29) 
 
Schedule at least the next follow-up visit; more if subject agrees 
 
Record vital signs and results of physical examination 
 
Administer C-SSRS (since last assessment)  
 
Discharge subjects if vital signs and physical exam are acceptable 
 
Outpatient Follow-up (Days 28, 35, 42, 49, 56, 63 [±2 days]) 
 
Record vital signs and results of physical examinations 
 
Assess severity of Substance Use Disorders using DSM-5 criteria since last administration of the 
questionnaire (Days 28 (or Day 35 if subject participated in inpatient extension stay) and 63 only) 
 
Administer standardized drug assessment of METH and other drug use since last visit (Days 28 (or 
Day 35 if subject participated in inpatient extension stay) and 63 only) 
o Note to administrator, if subject has reported multiple instances of METH use since last visit, 
instruct them to recall their first time of use since last visit.  Ask the following questions: 
o “Did you take your typical dose of METH as you normally would before you started the study?” 
Answer: Yes or No 
o If No, “Did you try more or less than normal?”  A: More or Less 
o “How was the high compared to what you typically get from that dose?”  Answer: Scale of 1-5; 1 
= Less than expected, 3 = Just as expected, 5 = Better than expected 
o If 1 or 2, “Did you take more METH to get the high you wanted?” Answer: Yes or No 
 
If Yes, “Did that get the result you wanted?”  Answer: Yes or No 

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 
Alcohol breath test 
 
Collect blood/urine for urine drug screen, and clinical laboratory assessments 
o A positive drug screen at a follow-up visit will not exclude the subject from completing the 
remainder of the study 
 
Collect blood for IXT-m200 PK 
 
Collect blood for HACA (Days 28 and 63 only; if those visits are missed, collect at next visit) 
 
Educate subjects on risk of taking METH or other abused drugs 
 
Schedule next follow-up(s) 
 
Outpatient Follow-up (Days 84, 105 [±3 days]) 
 
Record vital signs and results of physical examinations 
 
Assess severity of Substance Use Disorders using DSM-5 criteria since last administration of the 
questionnaire (Day 105 only) 
 
Administer standardized drug assessment of METH and other drug use since last visit (Day 105 only) 
o Note to administrator, if subject has reported multiple instances of METH use since last visit, 
instruct them to recall their first time of use since last visit.  Ask the following questions: 
o “Did you take your typical dose of METH as you normally would before you started the study?” 
Answer: Yes or No 
o If No, “Did you try more or less than normal?”  A: More or Less 
o “How was the high compared to what you typically get from that dose?”  Answer: Scale of 1-5; 1 
= Less than expected, 3 = Just as expected, 5 = Better than expected 
o If 1 or 2, “Did you take more METH to get the high you wanted?” Answer: Yes or No 
 
If Yes, “Did that get the result you wanted?”  Answer: Yes or No 
 
Alcohol breath test 
 
Collect blood/urine for urine drug screen, and clinical laboratory assessments 
o A positive drug screen at a follow-up visit will not exclude the subject from completing the 
remainder of the study 
 
Collect blood for IXT-m200 PK 
 
Educate subjects on risk of taking METH or other abused drugs 
 
Schedule next follow-up(s) 
 
7.3.4 FINAL STUDY VISIT 
 
Outpatient Follow-up (Day 126 [±3 days] or as soon as possible) 
 
Record vital signs and results of physical examinations 
 
Alcohol breath test 
 
Collect blood/urine for urine drug screen, and clinical laboratory assessments 
 
Collect blood for IXT-m200 PK 
 
Collect blood for HACA 
 
If ongoing AEs or SAEs are present, schedule follow-ups to continue monitoring until resolved 
 
7.3.5 EARLY TERMINATION VISIT 
 
Early Termination During Inpatient Stay 
 
Record vital signs, and results of physical examination, and clinical laboratory assessments 
 
Collect all scheduled blood and urine samples if subject is willing to remain in the unit 
 
Collect blood for HACA 

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 
Encourage the subject to remain in the unit for the planned duration of inpatient stay if IXT-m200 
dose has been administered 
 
Educate subjects on risk of taking METH or other abused drugs 
 
Provide references for METH use treatment and facilitate entry if subject is willing 
 
Schedule follow-up visits if IXT-m200 has been administered and subject is willing 
 
Early Termination During Outpatient Phase 
 
Record vital signs, and results of physical examination 
 
Administer standardized drug assessment of METH and other drug use since last visit 
 
Alcohol breath test 
 
Collect blood/urine for urine drug screen, and clinical laboratory assessments 
 
Collect all scheduled blood samples 
 
Collect blood for HACA 
 
Educate subjects on risk of taking METH or other abuse drugs 
 
Provide references for METH use treatment and facilitate entry if subject is willing 
 
7.3.6 SCHEDULE OF EVENTS TABLE 
 
Inpatient Stay (Day -1 – Day 22) 
a. 
Drug use history will be taken to assess drug use over the past 30 days using DSM-5 criteria (Section 7.1.1). 
During follow-ups, drug use history will be collected on Days 28, 63, and 105 only. 
 
 
Inpatient Timeline (Days) 
Follow-up (Days) 
 
Screening 
-1 
1 
2 
3 
4 
5, 
12, 
19 
6, 
13, 
20 
22p 
28, 35, 42, 
49, 56, 63 
(±2 days) 
84, 105, 
126 
(±3 days), 
ETq 
Admit 
 
X 
 
 
 
 
 
 
 
 
 
ICF 
X 
 
 
 
 
 
 
 
 
 
 
Drug use assessmenta 
X 
X 
 
 
 
 
 
 
 
X 
X 
Psychiatric evaluationb 
X 
 
 
 
 
 
 
 
X 
 
 
Physical examc 
X 
X 
 
X 
 
 
 
X 
X 
X 
X 
Vital signsd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical labse 
X 
X 
 
X 
 
 
 
X 
 
X 
X 
Drug and ETOH screensf 
X 
X 
 
 
 
 
 
 
 
X 
X 
ECGg 
X 
X 
X 
X 
 
X 
X 
X 
 
 
 
Telemetryh 
 
X 
X 
 
 
X 
X 
 
 
 
 
AE monitoringi 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
METH challengej 
 
 
X 
 
 
 
X 
 
 
 
 
mAb dosek 
 
 
 
 
 
X 
 
 
 
 
 
Blood for PKl 
 
 
X 
 
 
X 
X 
X 
 
X 
X 
Blood for HACAm 
 
 
 
 
X 
 
 
 
 
X 
X 
Urine collection for PKn 
 
 
X 
 
 
 
X 
X 
 
 
 
DEQo 
 
 
X 
 
 
 
X 
 
 
 
 
Blood for cytokinesr 
 
 
 
 
 
X 
 
 
 
 
 
Dischargep 
 
 
 
 
 
 
 
 
X 
 
 
AE = adverse event; DEQ = drug effects questionnaire; ECG = electrocardiogram; ET = early termination visit; 
ETOH = ethanol; HACA = human anti-chimeric antibody; ICF = informed consent form; mAb = monoclonal 
antibody; METH = methamphetamine; PK = pharmacokinetic 

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b. Psychiatric evaluations will be taken during medical history and will include the C-SSRS at Screening and 
again on Day 22 (C-SSRS will not be done on Day 22 if subject elects to participate in the inpatient extension 
stay). (Section 7.1.1). 
c. 
Physical exams will be done once per day as described (Section 7.1.1). 
d. Vital sign measurements will be obtained every 0.25 hours during IXT-m200 dosing, then 0.25, 0.5, 1, 2, and 
4 hours (±5 min) after dosing is completed, and as needed afterward until acceptable. On Days 1, 5, 12, and 19, 
vital signs will be measured within 30 min prior to the first dose, then 0.25, 1, 2, 4, 4.25, 5, 6, and 8 hours (±5 
min) relative to the first METH challenge dose. Measurements will be done at least daily during the inpatient 
stay and at each follow-up visit (Section 7.1.1). 
e. 
Clinical laboratory assessments will be done once per day as described in Section 7.2.1. 
f. 
Qualitative urine drug and breath alcohol tests will be performed as described in Section 7.2.1. 
g. Electrocardiograms (12-lead) will be recorded at screening, on Day -1, then 3, 12, and 24 hours (±10 min) after 
IXT-m200 dosing on Day 4. (The 24 hour ECG will only be done at the Investigator’s request for safety 
concerns, or if Day 5 dosing is not conducted). On Days 1, 5, 12, and 19, ECGs will be recorded within 30 min 
prior to the first dose, then 1, 5, 8, and 24 hours (±10 min) relative to the first METH challenge dose (Section 
7.1.1). 
h. Telemetry monitoring will be performed for a minimum of 4 hours on Day -1. Telemetry monitoring will be 
continuous from 0.5 hours before IXT-m200 or METH dosing to 8 hours and until normal: defined as heart rate 
within 20% of baseline at the final time point. Telemetry will be monitored as it is recorded, and a physician 
will review the data after completion of the recording (Section 7.1.1). 
i. 
Adverse event monitoring will be continuous from Day -1 through Day 126. 
j. 
METH challenges will consist of 0 and 30 mg IV METH (randomized) and will be administered 4 hours apart 
(Section 6.1.5). 
k. IXT-m200 will be administered as a 2-hour IV infusion (Section 6.1.5). 
l. 
Serial blood samples will be taken for assessment of IXT-m200 and METH PK (Section 7.1.1). 
 
Pharmacokinetic samples for IXT-m200 will be taken predose (up to 10 min prior), then 2.25, 4, and 6 
(± 0.0833), then 12 and 24 (± 0.167), and 72 (± 0.25) hours post start of the infusion. Subsequently, 
samples will be taken weekly until discharge (Days 12 and 19 before the first METH dose), then at each 
follow-up visit. 
 
Pharmacokinetic samples for METH will be taken -0.25 (± 0.08333), then 0.0833, 0.25, 0.5 and 1 
(± 0.0333), then 2 and 4 (± 0.0833), then 4.0833, 4.25 and 5 (± 0.0333), then 6 and 8 (± 0.0833), then 12, 
16 and 24 (± 0.167), then 36 and 72 (± 0.25) hours relative to the first METH dose. The second METH 
dose should be administered at 4 hours so that the subsequent sample is taken 5 minutes later (4.0833 hour 
time point). 
m. Blood samples for measurement of HACA will be taken on Days 3 (baseline), 28, 63, and 126 (Section 7.1.1); if 
a sample is missed, it should be collected at the next visit. 
n. Urine will be collected for analysis of METH excretion. Total urine collections will occur in increments of pre-
dose (spot), 0-4, 4-8, 8-12, 12-16, 16-24, 24-36 hours relative to the first METH dose on each METH challenge 
day (Section 7.1.1). 
o. Subjective effects of METH will be measured by the DEQ which will be administered within 30 min prior to 
the first dose, then 15, 30, 45, 60, 90, 120, and 180 minutes relative to each METH dose (Section 7.1.1). 
p. Subjects who wish to remain in the Inpatient Extension Stay will not discharge; instead they will be subject to 
the procedures listed in the Inpatient Extension Stay table below. 
q. Early termination visits may occur at any point during the study (Section 7.3.5). 
r. 
A blood sample will be taken prior to the IXT-m200 dose for cytokine baseline values (sample will not be 
analyzed if no infusion reaction occurs). If an infusion reaction occurs, samples will be taken at 1 and 4 hr post-
start of the reaction for cytokine analysis (Section 7.1.1).  
 
 
 

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Inpatient Extension Stay (Day 22 - Day 29) 
AE = adverse event; DEQ = drug effects questionnaire; ECG = electrocardiogram; ET = early termination visit; 
ETOH = ethanol; HACA = human anti-chimeric antibody; ICF = informed consent form; mAb = monoclonal 
antibody; METH = methamphetamine; PK =  pharmacokinetic. 
 
a. During follow-ups drug use history will be collected on Days 35, 63, and 105 only. 
b. The C-SSRS only will be administered on Day 29 (Section 7.1.1). 
c. Physical exams will be done once per day as described (Section 7.1.1). 
d. On Day 26 vital signs will be measured within 30 min prior to the first dose, then 0.25, 1, 2, 4, 4.25, 5, 6, and 8 
hours (±5 min) relative to the first METH challenge dose. Measurements will be done at least daily during the 
inpatient stay and at each follow-up visit (Section 7.1.1). 
e. Clinical laboratory assessments will be done once per day as described in Section 7.2.1. 
f. 
Qualitative urine drug and breath alcohol tests will be performed as described in Section 7.2.1. 
g. On Day 26, ECGs will be recorded within 30 min prior to the first dose, then 1, 5, 8, and 24 hours (±10 min) 
relative to the first METH challenge dose (Section 7.1.1). 
h. Telemetry monitoring will be continuous from 0.5 hours before IXT-m200 or METH dosing to 8 hours and 
until normal: defined as heart rate within 20% of baseline at the final time point. Telemetry will be monitored as 
it is recorded, and a physician will review the data after completion of the recording (Section 7.1.1). 
i. 
Adverse event monitoring will be continuous from Day -1 through Day 126. 
j. 
METH challenges will consist of 0 and 30 mg IV METH (randomized) and will be administered 4 hours apart 
(Section 6.1.5). 
k. Serial blood samples will be taken for assessment of IXT-m200 and METH PK (Section 7.1.1). 
 
Pharmacokinetic samples for IXT-m200 will be taken on Day 26 before the first METH dose, then at each 
follow-up visit. 
 
Pharmacokinetic samples for METH will be taken -0.25 (± 0.08333), then 0.0833, 0.25, 0.5 and 1 
(± 0.0333), then 2 and 4 (± 0.0833), then 4.0833, 4.25 and 5 (± 0.0333), 6 and 8 (± 0.0833), then 12, 16 and 
24 (± 0.167), then 36 and 72 (± 0.25) relative to the first METH dose. The second METH dose should be 
administered at 4 hours so that the subsequent sample is taken 5 minutes later (4.0833 hour time point). 
l. 
Blood samples for measurement of HACA will be taken on Days 28, 63, and 126 (Section 7.1.1); if a sample is 
missed, it should be collected at the next visit. 
m. Urine will be collected for analysis of METH excretion. Total urine collections will occur in increments of pre-
dose (spot), 0-4, 4-8, 8-12, 12-16, 16-24, 24-36 hours relative to the first METH dose on each METH challenge 
day (Section 7.1.1). 
 
Inpatient Extension Stay (Days) 
Follow-up (Days) 
22 
26 
27 
28 
29 
35, 42, 49, 56, 63 
(±2 days) 
84, 105, 126 
(±3 days), ET 
ICF 
X 
 
 
 
 
 
 
Drug use assessmenta 
 
 
 
 
 
X 
X 
Psychiatric evaluationb 
 
 
 
 
X 
 
 
Physical examc 
X 
 
X 
 
X 
X 
X 
Vital signsd 
X 
X 
X 
X 
X 
X 
X 
Clinical labse 
 
 
X 
 
 
X 
X 
Drug and ETOH screensf 
 
 
 
 
 
X 
X 
ECGg 
 
X 
X 
 
 
 
 
Telemetryh 
 
X 
 
 
 
 
 
AE monitoringi 
X 
X 
X 
X 
X 
X 
X 
METH challengej 
 
X 
 
 
 
 
 
Blood for PKk 
 
X 
X 
 
X 
X 
X 
Blood for HACAl 
 
 
 
X 
 
X 
X 
Urine collection for PKm 
 
X 
X 
 
 
 
 
DEQn 
 
X 
 
 
 
 
 
Discharge 
 
 
 
 
X 
 
 

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n. Subjective effects of METH will be measured by the DEQ which will be administered within 30 min prior to 
the first dose, then 15, 30, 45, 60, 90, 120, and 180 minutes relative to each METH dose (Section 7.1.1). 
 
7.4 
JUSTIFICATION FOR SENSITIVE PROCEDURES 
 
Use of placebo for IXT-m200 is justified in this study to create a comparator control group who also 
receives the METH challenge doses. Subjects recruited for this study will be non-treatment seeking for 
their METH use disorder. A single dose of IXT-m200 is not likely to benefit subjects who do not wish to 
change their METH intake. Therefore, the use of placebo for IXT-m200 does not place subjects at further 
risk nor does it prevent them from receiving a likely benefit. 
 
Placebo is also used for METH challenge dosing to control for anticipatory cardiovascular and subjective 
responses. The use of placebo for METH does not place subjects at further risk nor does it prevent them 
from receiving a likely benefit. 
 
7.5 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES  
 
All concomitant medications (ie, prescription medications, over-the-counter medications, and 
non-prescription medications) taken during study participation will be recorded on the eCRF. For this 
protocol, a prescription medication is defined as a medication that can be prescribed only by a properly 
authorized/licensed clinician.  
 
7.5.1 PRECAUTIONARY MEDICATIONS, TREATMENTS, AND PROCEDURES 
 
IXT-m200 may alter the PK of molecules that are structurally similar to METH, therefore subjects should 
not take drugs such as amphetamine or MDMA.  
 
7.6 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES  
 
Subjects are prohibited from the following during the study period: 
 
Ingesting or using any other investigational drug or device. 
 
Donating blood, plasma, platelets, eggs or sperm. 
 
Subjects will be encouraged to limit their ethanol consumption to approximately 1 drink per day for 
women and 2 drinks per day for men while in the study. 
 
7.7 
RESCUE MEDICATIONS, TREATMENTS, AND PROCEDURES  
 
 
If a Grade 2 infusion reaction occurs (see section 8.2.1 for grading scale), the IXT-m200 or control 
infusion will be temporarily discontinued. Depending on the progression of the symptoms after the 
infusion has been stopped, diphenhydramine (25 to 50 mg po or IV); acetaminophen (500 mg po); 
and/or methylprednisolone (125 mg IV) may be given if deemed necessary by the PI. If the symptoms 
resolve with discontinuation of the infusion, diphenhydramine and acetaminophen will be 
administered and the infusion restarted at the next lower rate than the one at which the symptoms 
occurred. 
 
If a Grade 3 infusion reaction occurs (see section 8.2.1 for grading scale), the infusion will be stopped 
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Methylprednisolone (125 mg IV), and/or diphenhydramine (25 mg IV) may be given along with 
bronchodilators and pressors as needed.  
 
With infusion reactions of any Grade, blood samples will be drawn at 1 and 4 hours after the 
beginning of the reaction to quantify levels of inflammatory cytokines. Cytokine IL-1B, IL-2, IL-4, 
IL-5, IL-6, IL-8, IL-10, IL-12, and TNFα levels will be determined. (TNFα typically rises within 
1 hour and IL-2, -6 and -10 within 4 hr). 
 
Hypotension (blood pressure less than 80/50 mmHg or less than 90/60 mmHg with symptoms of 
dizziness, near syncopy, or nausea, for example) will be treated initially with a fluid bolus  
(500 to 1000 cc). If hypotension persists, it will be treated with incremental doses of phenylephrine 
(100 µg IV) if the heart rate is greater than 100 beats per minute (bpm) or ephedrine (5 mg IV) if the 
heart rate is less than 80 bpm. Continuous heart rate and frequent blood pressure monitoring will 
accompany the treatment, and subsequent pharmacologic management will be dictated by the 
responses to the initial treatment. This could include doses of epinephrine (10 µg IV or sc) if the 
patient is unresponsive to the previous measures. 
 
Bronchospasm with hypoxemia (pulse oximeter readings less than 93% with dyspnea or tachypnea) 
will be treated with administration of oxygen via facemask or nasal cannula, along with albuterol 
inhalers or nebulized breathing treatments if necessary. Epinephrine (10 µg) doses may be given if the 
event is life-threatening or if the patient is unresponsive to the previous measures. 
 
Flushing, pruritis, urticaria will be treated with antihistamines (eg, diphenhydramine 25 to 50 mg, po, 
and/or famotidine 20 mg, po) or steroids (eg, prednisone 0.5 mg/kg, po) if not associated with other 
life-threatening sequelae.   
 
In any case in which hypotension do not resolve with the initial treatments outlined above, and they 
persist for longer than 30 minutes after sufficient treatment (as determined by the PI), 911 will be 
called and the subjects will sent to the nearest emergency room via ambulance for definitive 
treatment.  
 
If subjects exhibit signs or symptoms of METH withdrawal (eg, depression or anhedonia) during the 
IXT-m200 infusion, the infusion will be stopped and the subject treated appropriately. Immediate care 
will involve acknowledgment of symptoms, emotional support, and observation. Because symptoms 
of withdrawal are typically not medically dangerous, this treatment may suffice. There are no 
approved medications for symptoms of METH withdrawal, but mirtazapine (15 mg po qd), modafinil 
(100 mg po qd) or buproprion (100 mg po bid) may be started if medically indicated in the opinion of 
the PI.31 
 
If subjects exhibit signs or symptoms of METH-induced psychosis during their inpatient stay, no 
further METH challenges will be administered and if the symptoms occur prior to IXT-m200 dosing, 
the IXT-m200 dose will not be administered. Observation and emotional support will be given to the 
patient. There are no approved medications for the treatment of METH-induced psychosis. Acute 
agitation may be treated with small doses of haloperidol until the symptoms lessen (1-5 mg IV over 2-
5 min with continuous ECG monitoring). Subjects will then be referred to psychiatric care for 
definitive diagnosis and treatment.32 
 
The research clinics have been designed with the special requirements of pharmacological studies in 
mind. Emergency medications that might be needed to treat mAb toxicity are kept in the clinic. A hospital 
maintained crash cart is available near the laboratories. Oxygen and emergency ventilation equipment 
(Ambubags) are immediately available. ACLS-certified providers and a team is available on site to treat 
life-threatening events during the in-patient component of the study. Subjects are treated in a reclining 
position and syncope is unlikely. Normal saline is used as the IV fluid and fluid boluses can be 
administered if any hypotension is seen. Subjects are not allowed to stand until deemed stable by the 
investigator. In the event that serious medical complications result from this study, 911 will be called.  
 

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7.8 
PARTICIPANT ACCESS TO STUDY AGENT AT STUDY CLOSURE  
 
IXT-m200 will not be available to participants following their completion of the study. 
 
8 
ASSESSMENT OF SAFETY 
 
8.1 
SPECIFICATION OF SAFETY PARAMETERS 
 
Safety parameters that are study endpoints: 
 
Heart rate, blood pressure, and temperature (Section 7.1.1) 
 
QT and QTc intervals (Section 7.1.1) 
 
Safety parameters that will be recorded in the safety reporting system:  
 
Physical exam and vital sign measurements (Section 7.1.1) 
 
AEs 
 
ECG and telemetry data (Section 7.1.1) 
 
Clinical laboratory data (Section 7.2.1) 
 
Immunogenicity (Section 7.1.1) 
 
8.1.1 DEFINITION OF ADVERSE EVENTS  
 
An AE is any untoward medical occurrence in a subject administered IXT-m200 and which does not 
necessarily have to have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of IXT-m200, whether or not related to the IXT-m200.   
 
The AE may be: 
 
a new illness; 
 
worsening of a sign or symptom of the condition under treatment or of a concomitant illness; 
 
an effect of the study medication, including comparator; or 
 
a combination of 2 or more of these factors. 
 
No causal relationship with IXT-m200 or with the clinical study itself is implied by the use of the term 
“AE”. Pre-existing conditions will not be reported as an AE unless there has been a substantial increase in 
the severity or frequency of the problem which has not been attributed to natural history. 
 
Surgical procedures themselves are not AEs; they are therapeutic measures for conditions that require 
surgery. The condition for which the surgery is required may be an AE. Planned surgical measures 
permitted by the clinical study protocol and the condition(s) leading to these measures are not AEs. 
 
Adverse events fall into the categories “nonserious” or “serious”. 
 
8.1.2 DEFINITION OF SERIOUS ADVERSE EVENTS  
 
An SAE is an AE that at any dose: 
 
 
results in death; 
 
is life-threatening; 

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 
requires subject hospitalization or prolongation of existing hospitalization; 
 
results in persistent or significant disability/incapacity; or 
 
is a congenital anomaly/birth defect.  
 
The term “life-threatening” in the definition of “serious” refers to an event in which the subject was at 
immediate risk of death at the time of the SAE; it does not refer to an SAE which hypothetically might 
have caused death if it were more severe. 
 
Medical and scientific judgment will be exercised in deciding whether other AEs, such as important 
medical events that may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the subject or may require intervention to prevent one of the other outcomes listed above. 
These will also usually be considered serious.  
 
8.1.3 DEFINITION OF UNANTICIPATED PROBLEMS 
 
Unanticipated problems involving risks to participants or others will include, in general, any incident, 
experience, or outcome that meets all of the following criteria:  
 
 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the participant population being studied;  
 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and  
 
Suggests that the research places participants or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized.  
 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT 
 
8.2.1 SEVERITY OF EVENT 
 
The general approach outlined by the Club Phase 1 (CP1) working group in the British Journal of Clinical 
Pharmacology in 201033 will be used to categorize the severity of all AEs. The stopping rules outlined in 
Section 8.5 will apply. 
 
The following criteria will be used: 
 
 
Grade 1: Transient or mild discomfort; does not interfere with daily activity; no medical 
intervention/treatment required, 
 
Grade 2: Mild to moderate limitation in activity, some assistance may be needed; no or minimal 
intervention/treatment required, including but not limited to mild analgesics, antacids or antibiotics, 
 
Grade 3: Marked limitation in activity, some assistance usually required; medical 
intervention/treatment required, 
 
Grade 4: Extreme limitation in activity, significant assistance required; significant medical 
intervention/treatment, likely requiring hospitalization.  
 
Regarding vital sign AEs, Section 7.7 defines blood pressure criteria for treatment with fluids and 
medications. If hypotension is not immediately responsive to medications, this will constitute a Grade 3 
reaction and it will be documented as such. Similarly, if bronchospasm (SaO2 < 93% on oxygen) occurs 

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and requires medications, this will constitute a Grade 3 reaction, and will be documented as such. The 
stopping rules outlined in Section 8.5 will apply. 
 
8.2.2 RELATIONSHIP TO STUDY AGENT 
 
Association or relatedness to the study drug will be graded as follows:   
 
DEFINITELY – The AE: 
 
is clearly related to the investigational agent or research intervention; 
 
has a temporal relationship to the administration of the study drug; 
 
follows a known pattern of response;  
 
occurs in the absence of an alternative cause.  
PROBABLY – The AE: 
 
follows a reasonable temporal sequence from study drug administration; 
 
abates upon discontinuation of the drug; 
 
cannot be reasonably explained by the known characteristics of the subject’s clinical state. 
POSSIBLY – The AE: 
 
follows a reasonable temporal sequence from study drug administration; 
 
could have been produced by the subject’s clinical state or by other modes of therapy 
administered to the subject. 
UNLIKELY – The AE: 
 
does not follow a reasonable temporal sequence from study drug administration; 
 
is readily explained by the subject’s clinical state or by other modes of therapy administered to 
the subject. 
UNRELATED – The AE: 
 
is definitely produced by the subject’s clinical state or by other modes of therapy administered to 
the subject. 
 
8.2.3 EXPECTEDNESS  
 
The Safety Monitoring Committee (SMC; Section 8.6) will be responsible for determining whether an AE 
is expected or unexpected. An AE will be considered unexpected if the nature, severity, or frequency of 
the event is not consistent with the risk information previously described for the study agent.  
 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a study participant presenting for medical care, or upon review by a Study Monitor. All AEs 
including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate eCRF. Information to be collected includes event description, time of onset, clinician’s 
assessment of severity, relationship to study product (assessed only by those with the training and 
authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs occurring while 
on study must be documented appropriately regardless of relationship. All AEs will be followed to 
adequate resolution.  
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any time 
during the study, it will be recorded as an AE. Unanticipated problems will be recorded in the data 
collection system throughout the study.  

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Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity. All AEs characterized as intermittent require documentation of onset and 
duration of each episode.  
 
The PI will record all reportable events with start dates occurring any time after informed consent is 
obtained until 7 (for nonserious AEs) or 30 days (for SAEs) after the last day of study participation. At 
each study visit, the Investigator will inquire about the occurrence of AE/SAEs since the last visit. Events 
will be followed for outcome information until resolution or stabilization.  
 
8.4 
REPORTING PROCEDURES 
 
8.4.1 ADVERSE EVENT REPORTING  
 
All AEs (whether serious or nonserious) that occur after the subject has been randomized into a treatment 
group must be documented on the appropriate pages of the eCRF. For all AEs, the PI will provide an 
assessment of the AE, its treatment and resolution, and its relationship to IXT-m200. Every attempt 
should be made to describe the AE in terms of a diagnosis. If appropriate, component symptoms should 
also be listed below the diagnosis. If only nonspecific signs or symptoms are present, then these should be 
recorded as a diagnosis. 
 
All subjects who have AEs, whether considered associated with the use of IXT-m200 or not, will be 
monitored to determine the outcome. The clinical course of the AE will be followed up according to 
accepted standards of medical practice, even after the end of the period of observation, until a satisfactory 
explanation is found or the PI considers it medically justifiable to terminate follow-up. Should the AE 
result in death, a full pathologist’s report should be supplied, if possible. 
 
Adverse events will be reviewed by the SMC and Sponsor between cohorts during the interim review. If 
the PI decides it necessary, AEs may be reviewed at any time by consultation with the SMC and Sponsor. 
 
8.4.2 SERIOUS ADVERSE EVENT REPORTING  
 
The study clinician will complete an SAE form within the following timelines:  
 
 
All deaths and immediately life-threatening events, whether related or unrelated, will be recorded on 
the designated SAE form and submitted to the SMC and Sponsor within 24 hours of site awareness. 
See Section 1 for contact information.  
 
Other SAEs regardless of relationship, will be submitted to the SMC and Sponsor within 72 hours of 
site awareness.  
 
All SAEs will be followed until satisfactory resolution or until the site Investigator deems the event to be 
chronic or the adherence to be stable. Other supporting documentation of the event may be requested by 
the SMC or Sponsor and should be provided as soon as possible.  
 
The study Sponsor will be responsible for notifying FDA of any unexpected fatal or life-threatening 
suspected AEs as soon as possible but in no case later than 7 calendar days after the Sponsor's initial 
receipt of the information. The Sponsor is responsible for notifying the FDA of serious, unexpected, AEs 
that are not fatal or life-threatening as soon as possible, but no later than 15 calendar days, after first 
knowledge by the Sponsor that the SAE case meets the minimum criteria for expedited reporting. 
 

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NIDA Project Officer (PO) Tanya (Tatiana) Ramey MD, PhD will be notified by the Sponsor within 72 
hours of the SAE occurrence, and also via NIDA’s online Serious Adverse Event Tracking and Reporting 
System (SAETRS).  
 
Information not available at the time of the initial report will be documented on a follow-up SAE form. 
SAE information previously sent to the Sponsor will not be duplicated. When a nonserious event becomes 
serious, details will be forwarded immediately to the Sponsor on the designated SAE report form. 
 
8.4.3 REPORTING OF PREGNANCY  
 
If a subject is found to be pregnant after they have received IXT-m200, they should complete the study, 
with no further METH challenge doses administered, and be followed to determine the outcome of the 
pregnancy if the subject is willing. Generally, follow-up will be no longer than 6 to 8 weeks after the 
estimated delivery date. While pregnancy itself is not considered an AE or SAE, any pregnancy 
complications will be recorded as an AE or SAE. 
 
Pregnancies should be reported by the Investigator to the Sponsor within 2 days of identification.  
 
8.5 
STUDY HALTING RULES  
 
The criteria outlined in section 8.2.1 will be used to categorize the severity of all AEs. No new enrollment 
and no further study drug will be administered if any 1 of the following events occurs, unless the event 
was clearly unrelated to study drug administration.  
 
 
Two (2) subjects experience a Grade 3 AE.  
 
One (1) subject experiences a Grade 4 AE.  
 
A death occurs.  
 
Events unrelated to study drug administration include those that are temporally unrelated to IXT-m200 
administration, such as events occurring prior to dosing; or events in which the subject is a passive victim, 
such as a passenger in a motor vehicle crash. 
  
If any of these conditions are met, the Sponsor, in consultation with both PIs and Medical Monitor, will 
suspend enrollment until a full safety review is performed. The study Sponsor will inform the Data and 
Safety Monitoring Board (DSMB) members within 24 hours of this occurrence and will provide the 
DSMB with AE listing reports. The DSMB will convene an ad hoc meeting by teleconference or in 
writing as soon as possible. The DSMB will provide recommendations for proceeding with the study. A 
decision to reinitiate enrollment will be made in consultation with the FDA. 
 
8.6 
SAFETY OVERSIGHT 
 
Safety oversight will be under the direction of the SMC which will provide a review of safety data 
between cohorts. The SMC will be comprised of the PIs from both sites, Project Manager, Study 
Coordinators, and Medical Monitor. After each cohort, interim safety reports will be prepared by the 
Study Coordinators and PIs. These safety reports typically consist of the following: 
 
 
Summary of vital sign data for each subject within the cohort; 
 
Summary of physical exam findings within each cohort; 

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 
Safety laboratory data for each subject within the cohort either in hard copy printouts or 
electronically; 
 
Summary of AEs for each subject within the cohort; 
 
Summary of any clinically significant ECG changes for each subject within the cohort; and 
 
Any other miscellaneous pertinent information for the dose group. 
 
The SMC will hold teleconferences with Dr. Gentry (Chief Medical Officer of InterveXion Therapeutics, 
Sponsor) after each cohort to discuss the interim safety reports and findings. The safety reports and any 
recommendations of the DSMB will be reviewed and discussed by the SMC. The PIs and Medical 
Monitor will sign and date the report prior to moving forward with the next cohort. 
 
A Data and Safety Monitoring Board (DSMB) composed of individuals with the appropriate expertise, 
likely including monoclonal antibody and methamphetamine clinical pharmacology, acute care medicine 
(cardiovascular and/or emergency), psychiatry or behavioral medicine, statistics, and a patient advocate or 
representative. The DMSB will operate under the rules of an approved charter that will be written and 
reviewed at the organizational meeting of the DSMB. The DSMB will provide its input to the study 
Sponsor. 
 
The DSMB will review unblinded data while the SMC will review blinded study data. The DSMB 
membership is further removed from the study, while the SMC members are on the ground at the study 
sites with interaction with the actual subjects. Each review group will provide a recommendation to the 
Sponsor based on their perspectives. The Sponsor, by the actions of it’s Chief Medical Officer, W. 
Brooks Gentry, will determine whether cohort enrollment should continue or if changes should be made.  
 
9 
CLINICAL MONITORING 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of the 
trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with applicable 
regulatory requirement(s). 
 
The study will be monitored by a Study Monitor. Throughout the course of the study, the Study Monitor 
will make frequent contact with the PIs. This will include telephone calls and on-site visits. During the 
on-site visits, the Study Monitor will perform source data verification (a comparison of the data in the 
electronic data capture systems with the volunteer’s medical records including verification of informed 
consent of participating volunteers). This will require direct access to all original records for each 
volunteer (eg, clinic charts). 
 
The Study Monitor will also perform drug accountability checks and will request to perform a review of 
the PI study file to assure completeness of documentation in all respects of clinical study conduct. 
 
Upon completion of the study, the Study Monitor will arrange for a final review of the study files, after 
which the files should be secured for the appropriate time period. The PI, or appointed delegate, will meet 
with the Study Monitor during the on-site visits and will cooperate in providing the documents for 
inspection and responding to inquiries. In addition, the PI will permit inspection of the study files by 
authorized representatives of the Sponsor or the regulatory agencies. 
 

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10 STATISTICAL CONSIDERATIONS  
 
10.1 STATISTICAL AND ANALYTICAL PLANS 
 
Complete details of the statistical analyses to be performed will be documented in a statistical analysis 
plan (SAP), which will be completed prior to unblinding of the study data. This document will include 
more detail of analysis populations, summary strategies, and any amendments to the proposed analyses 
listed here, if necessary. Any changes to the SAP will be outlined in the final study report. 
 
10.2 STATISTICAL HYPOTHESES 
 
This is primarily a PK and safety study that is not evaluating any formal hypotheses. 
 
Primary: 
1) Treatment with IXT-m200 will increase systemic METH exposure (Cmax, AUC) following METH 
administration compared to PBO. (Analysis will be Day 1 METH exposure compared to Day 5 [primary] 
and Day 12, Day 19, Day 26 [all secondary] for each dose level of IXT-m200 compared to PBO and for 
overall treatment effect of IXT-m200 compared to PBO.) 
 
Secondary: 
1) Treatment with IXT-m200 will decrease subjective effects of METH compared to PBO. (Analysis will 
be Day 1 METH subjective effects [Drug Liking, etc] minus Day 5, Day 12, Day 19, and Day 26 for each 
dose level of IXT-m200 compared to PBO and for overall treatment effect of IXT-m200 compared to 
PBO.)  
 
10.3 ANALYSIS DATASETS 
 
The study analysis populations will consist of: 
 
 
Qualification Safety Population: Subjects who receive at least one dose of METH on Day 1. 
 
Safety Population: All subjects who receive a dose of IXT-m200 on Day 4. 
 
Pharmacokinetic Population: the PK analysis set will include all subjects in the safety analysis set 
for whom at least 1 PK parameter can be calculated for METH or IXT-m200. 
 
Pharmacodynamic Population: the PD analysis set will include all subjects in the safety analysis 
set who have completed all subjective response measures after at least 1 METH challenge 
following IXT-m200 administration. 
 
Subject allocation, including determination of events constituting major protocol deviations that would 
impact PD results, will be based on a blinded review of the protocol deviation and subject completion 
listings prior to database lock. 
 
10.4 DESCRIPTION OF STATISTICAL METHODS 
 
10.4.1 GENERAL APPROACH 
 
Pharmacokinetic blood samples will be assayed for measurement of concentrations of METH or 
IXT-m200. Pharmacokinetic parameters will be calculated for these analytes including the following, if 
possible: 

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 
Cmax by inspection (without interpolation) 
 
tmax by inspection  
 
AUC from time 0 to the time of the last quantifiable drug concentration (AUC0-t) 
 
AUC from time 0 to infinity (AUC0-∞) 
 
percentage of AUC extrapolated  
 
terminal elimination rate constant (λz) and associated t½ 
 
clearance (CL) 
 
Vd 
 
Urine samples will be collected and assayed for measurement of urine concentration of METH.  The 
following PK parameters will be calculated for METH (only), if possible: 
 
 
amount excreted in urine (Ae) 
 
renal clearance (CLR) 
 
The secondary PD measures and endpoints for assessment of subjective response include measures of 
balance of drug effects, positive drug effects, negative drug effects, and craving effects as follows: 
 
 
Measures of balance of effects:  
 
Minimum (Emin), Area Under the Effect Curve (AUEC) and Time to Emax or Emin (TEmax/Emin) 
for ‘at the moment’ Drug Liking VAS 
 
Emax and Emin for Overall Drug Liking VAS  
 
Emax for Take Drug Again VAS 
 
Measures of positive effects: 
 
Emax, AUEC, and TEmax for High VAS 
 
Emax, AUEC, and TEmax for Stimulated VAS   
 
Measures of negative effects:  
 
Emax, AUEC, and TEmax for Dislike VAS  
 
Measures of craving effects:  
 
Emax, AUEC, and TEmax for Crave VAS  
 
10.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
 
The PK population will be used for METH PK analysis. Serum concentration data for METH will be 
listed for each subject by challenge day, IXT-m200 dose level, and nominal time point, and summarized 
by IXT-m200 dose level using descriptive statistics, including count (n), mean, standard deviation (SD), 
SE, median, minimum, maximum, geometric mean and coefficient of variation (CV%). Mean and 
individual serum concentration versus time profiles for each METH challenge day will be presented 
graphically on linear and semi-logarithmic scales. PK parameters for METH will be listed for each 
subject by challenge day and IXT-m200 dose level and summarized by METH challenge day and 
IXT-m200 dose level using descriptive statistics including the geometric mean and CV%, as appropriate.  
 
A general linear model will be used to compare METH exposure (Cmax and AUC) following treatment 
with IXT-m200 compared to PBO. The analysis will compare Day 5 (primary) and Day 12, Day 19, and 
Day 26 (all secondary) METH exposure for each dose level of IXT-m200 compared to PBO with Day 1 
METH exposure included as a covariate. The overall treatment effect of IXT-m200 compared to PBO will 
be assessed similarly.  
 

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10.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 
The treatment effect of IXT-m200 on the subjective effects of METH will be analyzed using a 2-sample 
t-test on the change from baseline values. The changes between Day 1 METH subjective effects (Drug 
Liking, etc) and Day 5, Day 12, Day 19, and Day 26 will be obtained first for each subject. The analysis 
will compare the change from baseline values between each dose level of IXT-m200 and PBO. The 
overall treatment effect of IXT-m200 compared of PBO will be assessed similarly.  
 
The PK population will be used for IXT-m200 PK analysis. Serum concentration data for IXT-m200 will 
be listed for each subject by treatment group, and nominal time point, and summarized by treatment 
group, dose level, and nominal time point using descriptive statistics, including count (n), mean, SD, SE, 
median, minimum, maximum, geometric mean, and CV%. Mean and individual serum concentration 
versus time profiles for each dose level will be presented graphically on linear and semi-logarithmic 
scales. Serum PK parameters for IXT-m200 will be listed for each subject by dose level and summarized 
by dose level using descriptive statistics including the geometric mean and CV%, as appropriate. 
Statistical comparisons of IXT-m200 treatment groups will not be conducted. 
 
10.4.4 SAFETY ANALYSES 
 
Safety assessments and time points are provided in Section 7.3.6. 
 
All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). Each AE will 
be counted only once, and the most severe will be counted in each subject and in each preferred term or 
system organ class category for the analyses of safety. Summaries will be presented for all AEs (overall 
and by severity), AEs determined by the Investigator to be related to IXT-m200 (ie, reasonable 
possibility) (defined as related or with missing relationship) (overall and by severity), serious AEs, and 
AEs causing withdrawal from the study. Summaries will be presented by treatment group and for all 
subjects. Subject listings of SAEs and AEs leading to withdrawal will be presented. 
 
In addition, due to a difference in the number of overall METH challenges administered, summaries will 
also be presented separately for subjects that opt to stay for the Inpatient Extension and subjects that elect 
to discharge from the clinic on Day 22. 
 
Changes in vital signs, and liver function test data will be summarized descriptively by treatment and time 
point. Changes in other clinical laboratory and ECG measurement data will be summarized descriptively 
by time point. All values will be compared with prespecified boundaries to identify potentially clinically 
significant values, and such values will be listed.  
 
Physical examination findings will be listed by subject and visit.  
 
Medical History will be coded to MedDRA terms. Coded medical history terms will be listed. Scores 
from the C-SSRS assessment will be listed by subject and visit. 
 
The use of concomitant medications will be summarized by therapeutic class and preferred term using 
descriptive statistics. Concomitant medications will include all medications taken from the time of 
IXT-m200 administration through follow-up.  
 
For continuous variables, descriptive statistics (n, mean, SD, SE, median, minimum, and maximum) will 
be provided for actual values and changes from baseline to each time point. For categorical variables, 
subject counts and percentages will be provided. 

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If any subject dies during the study, a listing of deaths will be provided and all relevant information will 
be discussed in the subject narrative included in the clinical study report (CSR). 
 
10.4.5 ADHERENCE AND RETENTION ANALYSES 
 
Disposition of each analysis population will be summarized using descriptive statistics. Data from 
subjects who discontinue from the study will also be summarized by last treatment received and reason 
for discontinuation. 
 
10.4.6 BASELINE DESCRIPTIVE STATISTICS 
 
Demography and baseline characteristics (age, sex, race, ethnicity, body weight, height, and BMI) will be 
summarized using descriptive statistics (number of subjects, mean, SD, median, minimum, and maximum 
for continuous variables, and the proportion of subjects for categorical variables) for the Safety 
population.  
 
10.4.7 MULTIPLE COMPARISON/MULTIPLICITY 
 
No adjustments will be made for multiple comparisons. 
 
10.5 SAMPLE SIZE 
 
This is primarily a PK and safety study that is not evaluating any formal hypotheses.  
 
It is planned that a targeted minimum of 10, 18, and 14 completers at the IXT-m200 6 mg/kg, 20 mg/kg, 
and PBO treatments, respectively, through Day 22 will be sufficient to observe any difference in METH 
PK between Day 1 METH administration and METH challenges administered on Day 5, 12, and Day 19 
following IXT-m200 administration on Day 4.  
 
In a previous study wherein METH challenges were administered following treatment with varenicline in 
17 subjects34, statistically significant reductions were observed in subjective measures of ‘Any Drug 
Effect’, ‘High’, ‘Stimulated’, and ‘Drug Liking’. Utilizing data from this study, the sample size proposed 
herein of 28 subjects across all IXT-m200 treatments should provide at least 80% power to detect 
treatment differences of ≥11 points in Emax of drug liking, at the 1-sided significance level of 0.025, using 
a paired means test and correlation of 0.5, and assuming a SD of Drug Liking Emax of 20 points.  
 
10.6 MEASURES TO MINIMIZE BIAS 
 
10.6.1 ENROLLMENT/ RANDOMIZATION/ MASKING PROCEDURES 
 
Each potential subject will be assigned a unique number in the screening process (screening number). 
This number will be used to identify the subject throughout the study. Subjects who qualify will be 
assigned a unique randomization number to identify the sequence of their treatments.  
 
10.6.2 BREAKING THE STUDY BLIND/PARTICIPANT CODE 
 
Unblinding of treatment assignment during the study is discouraged and should occur only if it is 
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the Sponsor, the PI, or Medical Monitor deems identification of the study drug to the subject as necessary 
for the purpose of providing urgent subject care, the pharmacy will inform the PI of the assignment, who 
will notify the Medical Monitor, Sponsor, and subject. The process of unblinding will be appropriately 
documented in the PI file. The date and reason for the unblinding must be recorded on the subject’s 
eCRF. When possible, the Medical Monitor and Sponsor should be notified prior to unblinding; 
otherwise, they must be notified within 24 hours after unblinding. 
 
11 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
 
The study protocol, documentation, data and all other information generated will be held in strict 
confidence. No information concerning the study or the data will be released to any unauthorized third 
party without prior written approval of the Sponsor. The Study Monitor or other authorized 
representatives of the Sponsor may inspect all documents and records required to be maintained by the 
Investigator, including but not limited to, medical records (office, clinic, or hospital) and pharmacy 
records for the subjects in this study. The clinical study sites will permit access to such records. 
Investigators will maintain all records pertaining to this study for a period of 2 years following the date a 
marketing application is approved for the study agent for the indication for which it is being investigated; 
or if no application is to be filed or if the application is not approved for such indication, until 2 years 
after the investigation is discontinued and FDA is notified. 
 
The complete data management (data capture, data entry, data validation, checks on plausibility, query 
handling, data editing after entry, coding, database closure, etc) will be defined in advance within the 
Data Management Plan. Data analysis will be performed in accordance with the SAP.  
 
12 QUALITY ASSURANCE AND QUALITY CONTROL 
 
The study may be audited by a Quality Assurance Department to assess adherence to the clinical study 
protocol and Quality System. During the conduct of the study, process-related audits may be performed. 
An audit certificate will be provided in the appendices of the final CSR outlining any audits and other 
related activities performed. 
 
The Sponsor (or contractors) may conduct site or contract research organization audits.  
 
Quality control (QC) principles will be applied throughout the performance of this study. Review 
procedures will be followed for all documents that are generated in relation with the study.  
 
The study sites will generate and implement a study-specific Quality Management Plan describing routine 
QC and quality assurance activities for assessing the quality of the study data, protections of human 
subjects, compliance with applicable federal regulations, and ICH E6 GCP guidelines. The PI will ensure 
all study personnel are appropriately trained and applicable documentations are maintained on-site. 
Clinical site monitors will verify that the clinical trial is conducted and data are generated, documented 
(recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory 
requirements. Data Management and control processes specific to this study, along with all steps and 
actions taken regarding data management and data QC, will be described in a Data Management Plan. An 
explanation will be given for all missing, unused, and spurious data in the relevant sections of the CSR. 
 

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13 ETHICS/PROTECTION OF HUMAN SUBJECTS  
 
13.1 ETHICAL STANDARD  
 
The Investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 
and/or the ICH E6 Guideline for GCP. 
 
13.2 INSTITUTIONAL REVIEW BOARD  
 
The protocol, ICF(s), recruitment materials, and all participant materials will be submitted to the IRB for 
review and approval. Approval of both the protocol and the consent form must be obtained before any 
participant is enrolled. Any amendment to the protocol will require review and approval by the IRB 
before the changes are implemented to the study. All changes to the consent form will be IRB-approved; a 
determination will be made regarding whether previously consented participants need to be re-consented. 
 
The Sponsor will be responsible for reporting IRB actions to the NIDA Program Officer. In addition, all 
significant protocol changes will be approved by NIDA prior to implementation, unless there is an 
immediate safety concern for participants.  
 
13.3 INFORMED CONSENT PROCESS  
 
13.3.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED 
TO PARTICIPANTS 
 
The written consent document will embody the elements of informed consent as described in the 
Declaration of Helsinki and will adhere to the ICH Harmonized Tripartite Guideline for GCP. Informed 
consent must be obtained before any protocol-specified procedures or interventions are carried out. 
Informed consent will be obtained in accordance with 21 CFR 50.25 and 45 CFR 46. 
 
The consent form will be written in a language the subject can understand and will contain: 
 
 
A statement that the trial involves research. 
 
An explanation of the purposes of the research. 
 
The trial procedures to be followed, including all invasive procedures. 
 
The subject’s responsibilities. 
 
Those aspects of the trial that are experimental. 
 
The reasonably foreseeable risks or inconveniences to the subject and, when applicable, to an 
embryo, fetus, or nursing infant. 
 
The reasonably expected benefits. When there is no intended clinical benefit to the subject, the 
subject should be made aware of this. 
 
The alternative procedure(s) or course(s) of treatment that may be available to the subject, and 
their important potential benefits and risks. 
 
The compensation and/or treatment available to the subject in the event of trial-related injury. 
 
The anticipated prorated payment, if any, to the subject for participating in the trial. 
 
The anticipated expenses, if any, for the subjects participating in the trial. 

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 
That the subject’s participation in the trial is voluntary and that the subject may refuse to 
participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the 
subject is otherwise entitled. 
 
That the monitor(s), the auditor(s), the Institutional Ethics Committee/IRB, and the regulatory 
authority(ies) will be granted direct access to the subject’s original medical records for 
verification of clinical trial procedures and/or data, without violating the confidentiality of the 
subject, to the extent permitted by the applicable laws and regulations and that, by signing a 
written ICF, the subject or the subject’s legally acceptable representative allows such access. 
 
That records identifying the subject will be kept confidential and, to the extent permitted by the 
applicable laws and/or regulations, will not be made publicly available. If the results of the trial 
are published, the subject’s identity will remain confidential. 
 
That the subject or the subject’s legally acceptable representative will be informed in a timely 
manner if information becomes available that may be relevant to the subject’s willingness to 
continue participating in the trial. 
 
The foreseeable circumstances and/or reasons for which the subject’s participation in the trial will 
be terminated. 
 
The person(s) to contact for further information regarding the trial and the rights of trial subjects, 
and whom to contact in the event of trial-related injury. 
 
The expected duration of the subject’s participation in the trial. 
 
The approximate number of subjects involved in the trial. 
 
The consequences of a subject’s decision to withdraw from the research and the procedures for 
orderly termination of participation by the subject. 
 
A statement that the particular treatment or procedure may involve risks to the subject (or to the 
embryo or fetus if the subject should become pregnant) which are currently unforeseeable.  
 
A statement that informs the subject that while the study drug, IXT-m200, is present in their 
system they may react very differently to their typical doses of methamphetamine and that this 
response may change over time. Further, the ICF will state that it is possible that binge use of 
METH after receiving IXT-m200 could be extremely dangerous and possibly life-threatening.  
 
Neither the Investigator, nor the trial staff, should coerce or unduly influence a subject to participate or 
continue to participate in the trial. The subjects will sign and date the IRB-approved consent form after 
having their questions answered. Subjects will be provided copies of the signed and dated consent form 
and any amendments. Original consent forms will be kept on file by the Investigator for possible 
inspection by Regulatory Authorities and/or the Sponsor and Regulatory Compliance persons. 
 
13.3.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study 
and continues throughout the individual’s study participation. Extensive discussion of risks and possible 
benefits of participation will be provided to the participants and their families. Consent forms will be 
IRB-approved and the participant will be asked to read and review the document. The Investigator will 
explain the research study to the participant and answer any questions that may arise. All participants will 
receive a verbal explanation in terms suited to their comprehension of the purposes, procedures, and 
potential risks of the study and of their rights as research participants. Participants will have the 
opportunity to carefully review the written consent form and ask questions prior to signing. The 
participants should have the opportunity to discuss the study with their surrogates or think about it prior to 
agreeing to participate. The participant will sign the ICF prior to any procedures being done specifically 
for the study. The participants may withdraw consent at any time throughout the course of the trial. A 
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participants will be protected by emphasizing to them that the quality of their medical care will not be 
adversely affected if they decline to participate in this study.  
 
13.4 PARTICIPANT AND DATA CONFIDENTIALITY  
 
Subject confidentiality is held strictly in trust by the participating investigators, their staff, and the 
Sponsor and their agents. This confidentiality is extended to cover testing of biological samples in 
addition to the clinical information relating to participating subjects. All personal details of subjects will 
be treated as confidential by the Investigator and staff, and handling of personal data will be in 
compliance with the Health Insurance Portability and Accountability Act of 1996 and applicable State of 
Utah Health Information laws. 
 
The study protocol, documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study or the data will be released to any unauthorized third 
party without prior written approval from the Sponsor. The Study Monitor or other authorized 
representatives of the Sponsor may inspect any documents maintained by the Investigator, such as 
available medical records (office, clinic, or hospital) and pharmacy records for the subjects in this study. 
The clinical study site will permit access to such records. 
 
Certificate of Confidentiality: To further protect the privacy of study participants, a Certificate of 
Confidentiality is granted by the NIH to all awardees conducting research that collects or uses 
identifiable, sensitive information. This study is funded by an NIH cooperative agreement with the federal 
award identifier number U01DA045366. This certificate protects identifiable research information from 
forced disclosure. It allows the Investigator and others who have access to research records to refuse to 
disclose identifying information on research participation in any civil, criminal, administrative, 
legislative, or other proceeding, whether at the federal, state, or local level. By protecting researchers and 
institutions from being compelled to disclose information that would identify research participants, 
Certificates of Confidentiality help achieve the research objectives and promote participation in studies by 
helping assure confidentiality and privacy to participants. 
 
13.4.1 RESEARCH USE OF STORED HUMAN SAMPLES, SPECIMENS OR DATA 
 
Blood and urine specimens remaining after clinical safety assessments are performed will be stored only 
until the CSR is approved and submitted. 
 
Blood and urine specimens remaining after PK assessments are performed will be stored by Charles River 
Laboratories for at least 12 months for future drug metabolism and PK analysis. 
 
No genetic analysis will be performed. 
 
13.5 FUTURE USE OF STORED SPECIMENS  
 
Biological samples will be retained for no longer than 12 months following approval of the CSR and will 
only be used, if necessary, for repeat testing. 
 

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14 DATA HANDLING AND RECORD KEEPING  
 
14.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data Management Responsibilities: Data Management is responsible for the accuracy, quality, 
completeness, and internal consistency of the data from this study. Data handling, including data QC, will 
comply with international regulatory guidelines, including ICH GCP guidelines. Data Management and 
control processes specific to this study, along with all steps and actions taken regarding data management 
and data QC, will be described in a Data Management Plan. The Data Management Plan will be written 
by the Data Management Department and finalized prior to performing any data validation. MedDRA 
will be used for coding of AEs and concomitant diseases.  
 
Data Capture Methods: All data will be collected on source documents and then entered in the eCRFs. 
 
Types of Data: An appendix to the Data Management Plan (Source Identification List) will identify any 
data to be recorded directly in the eCRF (ie, no prior written or electronic record of data), and which data 
should be considered source data. 
 
Study Records Retention: All documents concerning the study will be kept by each Investigator in 
appropriate archive facilities for at least 15 years after conduct of the study. The Sponsor will receive the 
completed eCRFs (upon request, as a PDF file). 
 
Protocol Deviations: A protocol deviation is any change, divergence, or departure from the study design 
or procedures defined in the protocol. All deviations will be compiled in a centralized location. 
 
Deviations will be classified by whether or not they meet the definition of important protocol deviations. 
Important protocol deviations are a subset of deviations that might significantly affect the completeness, 
accuracy, and/or reliability of the study data or that might significantly affect a subject's rights, safety, or 
well-being. Deviations will be categorized by type and will be reviewed on an ongoing basis. 
 
The Investigator will document and explain any deviation from the approved protocol and notify the 
Sponsor. Protocol deviation notification and reports are submitted to Health Authorities and/or relevant 
IRB according to applicable requirements/guidelines/law.  
 
14.2 STUDY RECORDS RETENTION  
 
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing applications in an 
ICH region, or until at least 2 years have elapsed since the formal discontinuation of clinical development 
of the investigational product. These documents should be retained for a longer period, however, if 
required by local regulations. No records will be destroyed without the written consent of the Sponsor, if 
applicable. It is the responsibility of the Sponsor to inform the Investigator when these documents no 
longer need to be retained.  
 
The following records must be retained by the PI:  
 
 
Signed ICFs for all subjects 
 
Screening log (if applicable), and enrollment log 
 
Record of official communications between the PI and the IRB 

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 
Composition of the IRB or other applicable statement  
 
Record of all significant communications between the PI and Sponsor  
 
List of Subinvestigators and other appropriately qualified persons to whom the PI has delegated 
significant trial-related duties, together with their roles in the study and their signatures 
 
Copies of CRFs and of documentation of corrections for all subjects 
 
Drug accountability records 
 
Record of any body fluids or tissue samples retained 
 
All other source documents (patient records, hospital record copies, laboratory records, etc) 
 
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP (Essential 
Documents for the Conduct of a Clinical Trial) 
 
If the PI is unable to continue to store the study records, he must contact the Sponsor to make alternative 
arrangements. Details of these arrangements should be documented. 
 
14.3 PROTOCOL DEVIATIONS  
 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or manual of procedures 
requirements. The noncompliance may be either on the part of the participant, an Investigator, or study 
site staff. As a result of deviations, corrective actions are to be developed by the site and implemented 
promptly.  
 
These practices are consistent with ICH E6:  
 
4.5 Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3  
 
5.1 Quality Assurance and Quality Control, Section 5.1.1  
 
5.20 Noncompliance, Sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the sites to use continuous vigilance to identify and report deviations within 2  
working days of identification of the protocol deviation, or within 2 working days of the scheduled 
protocol-required activity. All deviations must be addressed in study source documents, reported to the 
NIDA Program Official and Sponsor. Protocol deviations must be sent to the local IRB per their 
guidelines. The PIs and study staff are responsible for knowing and adhering to their IRB requirements.  
 
14.4 PUBLICATION AND DATA SHARING POLICY 
 
This study will comply with the National Institutes of Health (NIH) Public Access Policy, which ensures 
that the public has access to the published results of NIH funded research. It requires scientists to submit 
final peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central 
upon acceptance for publication.  
 
The Sponsor will be responsible for registering and reporting the study in a public registry such as 
ClinicalTrials.gov. 
 
15 STUDY ADMINISTRATION 
 
15.1 STUDY LEADERSHIP 
 
The Study Team will govern the conduct of the study. The Study Team will be composed of the PI, PRA 
Director of Global Scientific Affairs (or similar), Sponsor’s Chief Medical Officer, and Sponsor’s 

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Operations Director (or similar). The Study Team will meet as necessary to discuss significant safety 
issues, contemplated major protocol changes, or other items. 
 
16 CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore any actual conflict of interest of persons who have a role in the design,  
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the trial. The study leadership in conjunction with the 
NIDA has established policies and procedures for all study group members to disclose all conflicts of 
interest and will establish a mechanism for the management of all reported dualities of interest. 
 
 
 

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17 LITERATURE REFERENCES  
 
1. 
Owens SM, Atchley WT, Hambuchen MD, Peterson EC, Gentry WB. Monoclonal antibodies as 
pharmacokinetic antagonists for the treatment of (+)-methamphetamine addiction. CNS Neurol 
Disord Drug Targets. 2011;10(8):892-898. 
2. 
Laurenzana EM, Stevens MW, Frank JC, et al. Pharmacological effects of two anti-
methamphetamine monoclonal antibodies. Supporting data for lead candidate selection for clinical 
development. Hum Vaccin Immunother. 2014;10(9):2638-2647. doi:10.4161/hv.29707. 
3. 
Hambuchen MD, Rüedi-Bettschen D, Williams DK, Hendrickson H, Owens SM. Treatment of rats 
with an anti-(+)-methamphetamine monoclonal antibody shortens the duration of action of 
repeated (+)-methamphetamine challenges over a one month period. Vaccine. 2014;32(47):6213-
6219. doi:10.1016/j.vaccine.2014.09.025. 
4. 
Stevens MW, Tawney RL, West CM, et al. Preclinical characterization of an anti-
methamphetamine monoclonal antibody for human use. MAbs. 2014;6(2):547-555. 
doi:10.4161/mabs.27620. 
5. 
Stevens MW, Henry RL, Owens SM, Schutz R, Gentry WB. First human study of a chimeric anti-
methamphetamine monoclonal antibody in healthy volunteers. MAbs. 2014;6(6):1649-1656. 
doi:10.4161/19420862.2014.976431. 
6. 
Hatsukami DK, Jorenby DE, Gonzales D, et al. Immunogenicity and smoking-cessation outcomes 
for a novel nicotine immunotherapeutic. - PubMed - NCBI. Clin Pharmacol Ther. 2011;89(3):392-
399. doi:10.1038/clpt.2010.317. 
7. 
Hoogsteder PHJ, Kotz D, van Spiegel PI, Viechtbauer W, van Schayck OCP. Efficacy of the 
nicotine vaccine 3'-AmNic-rEPA (NicVAX) co-administered with varenicline and counselling for 
smoking cessation: a randomized placebo-controlled trial. Addiction. 2014;109(8):1252-1259. 
doi:10.1111/add.12573. 
8. 
Cornuz J, Zwahlen S, Jungi WF, et al. A vaccine against nicotine for smoking cessation: a 
randomized controlled trial. - PubMed - NCBI. Goodyear M, ed. 2008;3(6):e2547. 
doi:10.1371/journal.pone.0002547. 
9. 
Martell BA, Orson FM, Poling J, et al. Cocaine vaccine for the treatment of cocaine dependence in 
methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial. 
Arch Gen Psychiatry. 2009;66(10):1116-1123. doi:10.1001/archgenpsychiatry.2009.128. 
10. 
Kosten TR, Domingo CB, Shorter D, et al. Vaccine for cocaine dependence: A randomized 
double-blind placebo-controlled efficacy trial. Drug Alcohol Depend. 2014;140:42-47. 
doi:10.1016/j.drugalcdep.2014.04.003. 
11. 
Haney M, Gunderson EW, Jiang H, Collins ED, Foltin RW. Cocaine-specific antibodies blunt the 
subjective effects of smoked cocaine in humans. Biol Psychiatry. 2010;67(1):59-65. 
doi:10.1016/j.biopsych.2009.08.031. 
12. 
La Garza De R, Shoptaw S, Newton TF. Evaluation of the cardiovascular and subjective effects of 
rivastigmine in combination with methamphetamine in methamphetamine-dependent human 
volunteers. Int J Neuropsychopharmacol. 2008;11(6):729-741. doi:10.1017/S1461145708008456. 

STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy 
Version 9 
M200C-1801 
 
20 Aug 2019 
 
 
57 
13. 
La Garza De R, Zorick T, Heinzerling KG, et al. The cardiovascular and subjective effects of 
methamphetamine combined with gamma-vinyl-gamma-aminobutyric acid (GVG) in non-
treatment seeking methamphetamine-dependent volunteers. Pharmacol Biochem Behav. 
2009;94(1):186-193. doi:10.1016/j.pbb.2009.08.007. 
14. 
Newton TF, La Garza De R, Kalechstein AD, Nestor L. Cocaine and methamphetamine produce 
different patterns of subjective and cardiovascular effects. Pharmacol Biochem Behav. 
2005;82(1):90-97. doi:10.1016/j.pbb.2005.07.012. 
15. 
Worley MJ, Heinzerling KG, Roche DJO, Shoptaw S. Ibudilast attenuates subjective effects of 
methamphetamine in a placebo-controlled inpatient study. Drug Alcohol Depend. 2016;162:245-
250. doi:10.1016/j.drugalcdep.2016.02.036. 
16. 
Ray LA, Bujarski S, Courtney KE, et al. The Effects of Naltrexone on Subjective Response to 
Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study. - 
PubMed - NCBI. Neuropsychopharmacology. 2015;40(10):2347-2356. doi:10.1038/npp.2015.83. 
17. 
Kaufman MJ, Levin JM, Kukes TJ, et al. Illicit cocaine use patterns in intravenous-naive cocaine 
users following investigational intravenous cocaine administration. Drug Alcohol Depend. 
2000;58(1-2):35-42. 
18. 
Mendelson J, Jones RT, Upton R, Jacob P. Methamphetamine and ethanol interactions in humans. 
Clin Pharmacol Ther. 1995;57(5):559-568. doi:10.1016/0009-9236(95)90041-1. 
19. 
Johnson BA, Wells LT, Roache JD, et al. Kinetic and cardiovascular effects of acute topiramate 
dosing among non-treatment-seeking, methamphetamine-dependent individuals. Prog 
Neuropsychopharmacol Biol Psychiatry. 2007;31(2):455-461. doi:10.1016/j.pnpbp.2006.11.011. 
20. 
Cheng WS, Garfein RS, Semple SJ, Strathdee SA, Zians JK, Patterson TL. Binge use and sex and 
drug use behaviors among HIV(-), heterosexual methamphetamine users in San Diego. Subst Use 
Misuse. 2010;45(1-2):116-133. doi:10.3109/10826080902869620. 
21. 
Brecht M-L, O'Brien A, Mayrhauser von C, Anglin MD. Methamphetamine use behaviors and 
gender differences. Addictive Behaviors. 2004;29(1):89-106. 
22. 
Hser Y-I, Huang D, Brecht M-L, Li L, Evans E. Contrasting trajectories of heroin, cocaine, and 
methamphetamine use. J Addict Dis. 2008;27(3):13-21. doi:10.1080/10550880802122554. 
23. 
Vadhan NP, Hart CL, Roe B, Colley J, Haney M, Foltin RW. Substance use and psychosocial 
outcomes following participation in residential laboratory studies of marijuana, methamphetamine 
and zolpidem. Am J Drug Alcohol Abuse. 2006;32(4):589-597. doi:10.1080/00952990600920565. 
24. 
Novak SP, Kral AH. Comparing injection and non-injection routes of administration for heroin, 
methamphetamine, and cocaine users in the United States. J Addict Dis. 2011;30(3):248-257. 
doi:10.1080/10550887.2011.581989. 
25. 
Kang SP, Saif MW. Infusion-related and hypersensitivity reactions of monoclonal antibodies used 
to treat colorectal cancer--identification, prevention, and management. J Support Oncol. 
2007;5(9):451-457. 
26. 
Chung CH. Managing premedications and the risk for reactions to infusional monoclonal antibody 

STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy 
Version 9 
M200C-1801 
 
20 Aug 2019 
 
 
58 
therapy. The Oncologist. 2008;13(6):725-732. doi:10.1634/theoncologist.2008-0012. 
27. 
Lecluse LLA, Piskin G, Mekkes JR, Bos JD, De Rie MA. Review and expert opinion on 
prevention and treatment of infliximab‐related infusion reactions. British Journal of Dermatology. 
2008;159(3):527-536. doi:10.1111/j.1365-2133.2008.08728.x. 
28. 
Reilley S, Wenzel E, Reynolds L, Bennett B, Patti JM, Hetherington S. Open-label, dose 
escalation study of the safety and pharmacokinetic profile of tefibazumab in healthy volunteers. 
Antimicrob Agents Chemother. 2005;49(3):959-962. doi:10.1128/AAC.49.3.959-962.2005. 
29. 
Dowling TC, Chavaillaz PA, Young DG, et al. Phase 1 safety and pharmacokinetic study of 
chimeric murine-human monoclonal antibody c alpha Stx2 administered intravenously to healthy 
adult volunteers. Antimicrob Agents Chemother. 2005;49(5):1808-1812. 
doi:10.1128/AAC.49.5.1808-1812.2005. 
30. 
Subramanian GM, Cronin PW, Poley G, et al. A phase 1 study of PAmAb, a fully human 
monoclonal antibody against Bacillus anthracis protective antigen, in healthy volunteers. Clin 
Infect Dis. 2005;41(1):12-20. doi:10.1086/430708. 
31. 
Pennay AE, Lee NK. Putting the call out for more research: The poor evidence base for treating 
methamphetamine withdrawal. Drug Alcohol Rev. 2011;30(2):216-222. doi:10.1111/j.1465-
3362.2010.00240.x. 
32. 
Glasner-Edwards S, Mooney LJ. Methamphetamine Psychosis: Epidemiology and Management. 
CNS Drugs. 2014;28(12):1115-1126. doi:10.1007/s40263-014-0209-8. 
33. 
Sibille M, Patat A, Caplain H, Donazzolo Y. A safety grading scale to support dose escalation and 
define stopping rules for healthy subject first-entry-into-man studies. Br J Clin Pharmacol. 
2010;70(5):736-748. doi:10.1111/j.1365-2125.2010.03741.x. 
34. 
Verrico CD, Mahoney JJ, Thompson-Lake DGY, Bennett RS, Newton TF, La Garza De R. Safety 
and efficacy of varenicline to reduce positive subjective effects produced by methamphetamine in 
methamphetamine-dependent volunteers. Int J Neuropsychopharmacol. 2014;17(2):223-233. 
doi:10.1017/S146114571300134X.