Clinical trial NCT03336866
Conditions: Methamphetamine-dependence Methamphetamine Abuse
Sponsor: InterveXion Therapeutics, LLC
Start date: 2018-05-03; Completion date: 2021-03-09
Enrollment: 77 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study evaluates the ability of IXT-m200 to change methamphetamine concentrations in blood and alter the way methamphetamine feels. Participants will receive either placebo, a low or high dose of IXT-m200, in addition to methamphetamine challenge doses.

Detailed description:
IXT-m200 is a monoclonal antibody that binds to methamphetamine in the blood. The main purpose of this study is to look at the effects of IXT-m200 on the pharmacokinetics of methamphetamine and on methamphetamine liking effects. Additionally, the study will determine IXT-m200 pharmacokinetics, safety and tolerability in subjects with methamphetamine use disorder. Qualified subjects will receive a single dose of IXT-m200 followed by up to 4 methamphetamine challenge doses.

Arms: arm 1: Normal saline arm 2: Single 6 or 20 mg/kg intravenous dose of IXT-m200
Interventions: intervention 1: Placebo intervention 2: IXT-m200
Intervention descriptions: intervention 1: Normal saline intervention 2: IXT-m200 is an anti-methamphetamine monoclonal antibody

Protocol documents:
ICF_000.pdf: 
Study title: 
STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy 
Protocol number: 
NCT number: 
Document date: 
M200C-1801 
NCT03336866 
31May2018 (submitted 03May2021) 


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INFORMED CONSENT TO TAKE PART IN A RESEARCH STUDY 
 
TITLE OF STUDY: 
STAMPOUT: Study of Antibody for Methamphetamine 
Outpatient Therapy 
 
PROTOCOL: 
 
M200C-1801 
 
INVESTIGATOR:    
Lynn Webster, MD 
Pharmaceutical Research Associates, Inc. 
1255 E 3900 So. 
Salt Lake City, UT 84124 
 
 
PHONE NUMBER:  
(801) 269-8200 
 
AFTER HOURS: 
 
(801) 892-5151 
   
SPONSOR:                        InterveXion Therapeutics, LLC 
 
4301 W. Markham St. #831 
 
Little Rock, AR 72205 
 
Sponsor  
The pharmaceutical company sponsoring this study is InterveXion Therapeutics, 
LLC. The study doctor and Pharmaceutical Research Associates, Inc. are being 
paid by InterveXion Therapeutics, LLC to conduct this study. A description of this 
clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the 
Web site will include a summary of the results. You can search this Web site at 
any time.  This study can be found by using the identifier ‘NCT03336866’. 
 
What is the purpose of this form? 
You are being asked to take part in a research study. It is important that you read 
the following explanation of the proposed procedures. This form describes the 
purpose, procedures, benefits, risks, discomforts, and precautions of the study. It 
also describes your right to withdraw from the study at any time. A member of the 
study staff will read through the consent with you and discuss all the information. 
When you think you understand the study, you will then be asked if you agree to 
take part. If you agree, you will be asked to sign this consent form. Once you sign 
it, we will give you a signed and dated copy to keep. 
 
You may show this consent form to family, friends, and other doctors before you 
sign it. You may want to discuss it with them to help you decide if you want to be 
part of the study. If you don’t know another doctor but want a second opinion 
about this study, please ask. The study doctor will give you the name of another 
doctor that you can talk to. 


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What is being studied? 
IXT-m200 is an investigational drug. The word “investigational” means IXT-m200 
is not approved for sale by the U.S. Food and Drug Administration (FDA). The 
FDA has given permission to the sponsor, InterveXion Therapeutics, LLC, to use 
IXT-m200 in this study. IXT-m200 is an anti-methamphetamine monoclonal 
antibody. Monoclonal antibodies are medications that specifically stick to their 
target, in this case methamphetamine. This may decrease the effect. The effects 
of IXT-m200 will be compared to placebo, an inactive substance. 
 
Because this is a study, IXT-m200 will only be given to you during this study and 
not after the study is over.  
 
Why is this study being done? 
The main purpose of this study is to look at the effects of IXT-m200 (the 
investigational drug) on the pharmacokinetics of methamphetamine (METH). 
Pharmacokinetics looks at the amount of drug in the blood; how the drug may 
move in the body; and what kind of effects the drug will have on the body when 
administered intravenously.  This study will also look at the effects of IXT-m200 
on methamphetamine liking effects. Additionally, the study will also explore the 
amount of IXT-m200 in the blood compared to placebo (no active ingredients). 
This study will also look at how safe and tolerable IXT-m200 is in people who 
have methamphetamine use disorder. 
 
Throughout this consent form, IXT-m200 and placebo will be referred to as “study 
drug(s),” and methamphetamine and placebo will be referred to as “challenge 
drug(s).” 
 
What do you need to know about this study? 
Participants who take part in this study are otherwise healthy males and females 
between the ages of 21 and 50 who use methamphetamine; have METH use 
disorder; and are not seeking treatment.   
 
This study is being conducted at one study center. This study center will enroll 
approximately 126 participants.  Additionally, participants who complete the 
inpatient part of the study will be asked to take part in an additional 7-day 
inpatient period of the study. 
 
You are being asked to participate in the study because you have admitted to 
using methamphetamine. 
 
The study staff will review your current list of medicines, your medical, alcohol, 
tobacco and drug use history, and other information that may keep you from 
being in this study. 
 


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If there are any changes to your current medicines or your medical condition(s), 
please tell the study staff right away. If you don’t tell the study staff of any 
changes, you may harm yourself by being in the study. 
 
What will happen during this study? 
You may be asked to be in the study for up to 4.5 months. This includes: 
§ Screening Period up to 30 days (questions and tests to see if you are 
eligible for the study). You will not be confined to the study center during 
the Screening period. 
§ An in-patient period of up to 23 days and 22 nights.  For participants 
agreeing to take part in the Inpatient Extension Stay, the in-patient period 
will last up to 30 days and 29 nights. 
§ Up to 9 out-patient follow up visits 
§ Final study visit, approximately 126 days after the first dose of challenge 
drug. 
 
You will be asked to come to the clinic up to 11 times.  You may need to return to 
the study center for additional visits at the discretion of the study doctor. 
 
DOSING AND PROCEDURES 
 
METH Challenge: 
On Day 1 of the inpatient period, you will undergo a METH Challenge. This part 
of the study is to find out if you can tell the difference between methamphetamine 
and placebo (no active ingredient).  You will be randomly assigned (like flipping a 
coin) to receive either 30 mg methamphetamine or placebo (no active 
ingredients). You will receive both active and non-active doses during the METH 
Challenge. Each of these treatments will be separated by approximately 4 hours.  
The order in which you receive the challenge drugs is not known by you or the 
study doctor or staff.  In the case of a medical emergency, however, the study 
doctor can find out quickly what challenge drug you were given. 
 
Each of the two challenge drug treatments will consist of an intravenous (into a 
vein) infusion.  
 
The first dose will be given in the morning, approximately 1 hour after you have 
eaten a light meal or snack. The second dose will be given approximately 4 
hours after the first dose. You will be given a light meal or snack approximately 3 
hours after the morning dose and 1 hour before the afternoon dose. 
 
If you are eligible to continue on to the Treatment Phase of the study (see 
description below), you will undergo additional METH Challenges as described 
above on Days 5, 12 and 19 of the in-patient period.  If you are asked and agree 
to take part in the extended in-patient stay, you will undergo an additional METH 
Challenge on Day 26 of the extended in-patient period. 


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Treatment Phase: 
During the Treatment phase of the study, up to four groups of participants will be 
randomly (like flipping a coin) assigned to receive IXT-m200 or placebo as an 
intravenous (into a vein) infusion given over 2 hours.  You will be assigned to one 
of the groups below: 
 
Group 1:  
If you are assigned to Group 1, you will be randomly assigned to receive one of 
the treatments listed below: 
§ IXT-m200-6 mg per kg of body weight  
§ placebo  
 
About 12 participants will be assigned to receive IXT-m200 and 6 participants will 
be assigned to receive placebo. 
 
Group 2:   
If you are assigned to Group 2, you will be randomly assigned to receive one of 
the treatments listed below: 
§ IXT-m200-6 mg per kg of body weight  
§ IXT-m200-20 mg per kg of body weight 
§ placebo  
 
About 6 participants will be assigned to receive IXT-m200-6 mg/kg, 6 participants 
will be assigned to receive IXT-m200-20 mg/kg and 6 participants will be 
assigned to receive placebo. 
 
Group 3:   
If you are assigned to Group 3, you will be randomly assigned to receive one of 
the treatments listed below: 
§ IXT-m200-6 mg per kg of body weight  
§ IXT-m200-20 mg per kg of body weight 
§ placebo  
 
About 12 participants will be assigned to receive IXT-m200-6 mg/kg, 12 
participants will be assigned to receive IXT-m200-20 mg/kg and 12 participants 
will be assigned to receive placebo. 
 
Group 4:  
If you are assigned to Group 4, you will be randomly assigned to receive one of 
the treatments listed below: 
§ IXT-m200-20 mg per kg of body weight  
§ placebo  
 


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About 36 participants will be assigned to receive IXT-m200 and 18 participants 
will be assigned to receive placebo. 
 
You will take part in only one of the four groups listed above and receive only one 
of the study drug treatments listed above.  You will not be able to choose which 
group you are assigned to.  The treatment you are assigned is not known by you 
or the study doctor or staff.  In the case of a medical emergency, however, the 
study doctor can find out quickly what study drug you were given. 
 
You will receive your assigned study drug treatment on Day 4 of the inpatient 
period. You will be given a light meal or snack approximately 1 to 2 hours prior to 
dosing. You will be required to lie down or remain in a semi-sitting position while 
you receive the study drug and remain in such position for 2 hours following 
dosing.  Water will be restricted from 1 hour prior to dosing until 2 hours after 
dosing. You will receive a standardized lunch approximately 4 hours after dosing 
starts. 
 
STUDY PROCEDURES 
 
Screening Visit  
Before entering the study, you will be asked to read, sign, and date this consent 
form.  If you choose to continue, the screening evaluation process will include the 
following procedures: 
§ Your demographic information (age, sex, race and ethnicity) will be 
recorded. 
§ Your weight and height will be measured. Body Mass Index (BMI) will be 
calculated using your height and weight. 
§ Your medical and surgical history will be recorded, including history of 
alcohol and smoking status, and evaluation of drug and alcohol 
dependence. 
§ A psychiatric evaluation and an assessment of methamphetamine and 
other drug use. 
§ You will be asked questions about your history of suicide and suicidal 
thoughts. 
§ Any prescription or non-prescription medications you have taken within the 
past 12 months will be documented. 
§ Your vital signs will be taken after you have been lying down for 5 
minutes, including pulse, respiration (breathing) rate, blood pressure, oral 
temperature, and pulse oximetry (a clip will be placed lightly on your finger 
to measure your blood oxygen levels). 
§ An ECG (measures how your heart is beating) will be performed after you 
have been lying down for 5 minutes. Sticky patches will be applied to your 
chest and extremities; if your chest hair is heavy, it may be necessary to 
clip some hair so that the patches will stick to your skin.  Female subjects 
may need to remove bras for the ECG. 


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§ Routine clinical laboratory tests such as blood hematology, serum 
chemistry and urinalysis will be conducted.  For women, a blood sample 
will be collected for a pregnancy test. Approximately two teaspoons of 
blood will be collected. 
§ Blood tests for Hepatitis A, Hepatitis B, Hepatitis C, and HIV (the virus that 
causes AIDS) will be given.  Approximately 1 teaspoon of blood will be 
collected. If your test results show that you have Hepatitis or HIV, the 
study doctor will notify the local state health agency to report your 
condition.  The results of your test(s) will be made known to local health 
agencies as required by law. If needed, the study doctor or study staff 
member will either recommend treatment to you or refer you to your 
primary care provider. If you test positive for HIV or Hepatitis, you will not 
be included in the study. 
§ An alcohol breath test will be performed; the results will be kept with your 
study chart and will not be discarded. If you test positive, you may not be 
included in the study. 
§ A urine drug screen will be performed; the results will be kept with your 
study chart and will not be discarded.  If you test positive, you may not be 
included in the study. 
§ A physical exam will be performed. 
§ Study entry criteria will be reviewed. 
 
Screening does not guarantee entry into the study. Entry into the study will 
depend upon the results of your screening evaluation and the opinion of the 
study doctor. If you qualify to be in the study, you will return to the study center 
within 30 days of the screening visit for the in-patient part of the study. The in-
patient part may last up to 23 days and 22 nights if you qualify for all portions of 
the study. If you are asked and agree to take part in the extended in-patient 
period of the study, your inpatient part may last up to 30 days and 29 nights. 
 
In-Patient Visit (Up to 23 Days/22 nights total) 
 
Enrollment/Baseline (Day -1) 
You will be asked to return to the study center the day before receiving your first 
dose of challenge drug during the in-patient period.  
 
The following procedures will be performed at check-in: 
§ Study entry criteria will be reviewed. 
§ The list of prescription or non-prescription medications taken from the 
previous visit will be updated. 
§ Any changes in your health will be updated. 
§ An assessment of methamphetamine and other drug use for the past 30 
days will be done. 


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§ Vital signs will be collected after you have been lying down for 5 minutes. 
Vital signs include pulse, respiration (breathing) rate, blood pressure, oral 
temperature, and pulse oximetry. 
§ An ECG will be performed after you have been lying down for 5 minutes. 
§ A physical examination will be performed. 
§ Routine clinical laboratory tests such as blood hematology, serum 
chemistry and urinalysis will be conducted. Approximately two teaspoons 
of blood will be collected. For women, a blood sample for a pregnancy test 
will also be collected.  
§ A urine drug screen; if you test positive, you may not be eligible to 
continue with the study. The results will be kept with your study chart and 
will not be discarded. 
§ An alcohol breath test; if you test positive, you will not be eligible to 
continue with the study. The results will be kept with your study chart and 
will not be discarded. 
§ Telemetry will be monitored continuously for at least 4 hours.  Telemetry is 
the continuous monitoring of vital signs such as heart rate, blood pressure, 
and breathing and also looks at the electrical activity of your heart. 
 
If you do not continue to meet the study requirements after admission procedures 
are performed, you will not be able to continue in the study.  
 
In-patient Stay - Days 1, 2 and 3 
You will receive the challenge drugs as outlined in this consent form.  The 
following procedures will be completed: 
§ An IV catheter used for blood collection and challenge drug administration 
will be inserted into a vein.  You will have two IV catheters placed on Day 
1. 
§ Vital signs including pulse, respiration (breathing) rate, blood pressure, 
oral temperature, and pulse oximetry will be taken after you have been 
lying down for 5 minutes multiple times. 
§ ECG will be performed after you have been lying down for 5 minutes 
multiple times. 
§ Telemetry will be monitored continuously for at least 8 hours after METH 
Challenge dosing. 
§ A physical exam will be performed on Day 2. 
§ PK blood samples (a blood sample taken to measure the amount of drug 
in your blood) will be collected approximately 18 times.  A little over ½ 
teaspoon of blood will be collected each time.  
§ A blood sample to test for an immune reaction to the study drug will be 
collected on Day 3.  About one teaspoon of blood will be collected. 
§ Routine clinical laboratory tests such as blood hematology, serum 
chemistry and urinalysis will be conducted on Day 2. Approximately two 
teaspoons of blood will be collected. 


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§ All your urine starting just prior to the METH Challenge through 36 hours 
after dosing will be collected for urine PK samples.  Urine PK samples are 
to see how much methamphetamine gets into your urine. 
§ You will complete questionnaires several times about the way you are 
feeling and about the challenge drug. The questionnaires take 
approximately five to ten minutes to complete each time.  
§ You will be asked about any changes in your health. 
§ You will be asked about any changes in your medications. 
 
After all the study-related procedures are completed on Day 3, the study doctor 
will determine if you may continue to the treatment phase of the study.  If the 
study doctor determines that you cannot continue in the study, you will be asked 
to complete the early termination procedures (see End of Study Visit/ Early 
Termination section below).  You will be discharged from the study center on Day 
3 or when the study doctor feels it is okay for you to leave. 
 
Depending on the results of the METH Challenge, you may be asked to continue 
on to the treatment phase of the study. If you continue into this part of the study, 
you will stay in the study center. You will spend up to 23 days total in the study 
center during the in-patient stay, if you complete the treatment phase. If you are 
asked and agree to take part in the extended in-patient period, you will spend up 
to 30 days total in the study center during the in-patient stay. 
 
In-patient Treatment Phase – Days 4 through 22 
You will receive the challenge and study drug treatments as outlined in this 
consent form on Days 4, 5, 12 and 19.   
 
The following procedures will be completed: 
§ An IV catheter used for blood collection and challenge and study drug 
administration will be inserted into a vein.  You will have two IV catheters 
placed on dosing days. 
§ Vital signs including pulse, respiration (breathing) rate, blood pressure, 
oral temperature, and pulse oximetry will be taken after you have been 
lying down for 5 minutes multiple times. 
o When you are dosed on Day 4 with either placebo or study drug 
you will be asked to remain in a lying down or semi-reclining 
position for the entire 2 hour dosing period. During this dosing 
period of two hours vital signs will collected while you are in a 
lying down or semi-reclining position. 
§ ECG will be performed after you have been lying down for 5 minutes 
multiple times. 
§ Telemetry will be monitored continuously for at least 8 hours after each 
IXT-m200 and METH Challenge dosing. 
§ A physical exam will be performed multiple times. 


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§ PK blood samples (a blood sample taken to measure the amount of drug 
in your blood) will be collected approximately 63 times, with the most on 
any one day being about 15 times. A little over ½ to one teaspoon of blood 
will be collected each time.  
§ A blood sample to test for cytokines will be collected prior to dosing on 
Day 4.  Additional samples may be collected if necessary after dosing if 
you develop an infusion related reaction.  Cytokines help to regulate the 
immune system.  They are created in response to a stimulus such as 
inflammation. Approximately a little over 5 teaspoons of blood will be 
collected each time. 
§ Routine clinical laboratory tests such as blood hematology, serum 
chemistry and urinalysis will be conducted multiple times. Approximately 
two teaspoons of blood will be collected each time. 
§ All your urine starting just prior to each METH Challenge through 36 hours 
after dosing will be collected for urine PK samples. Urine PK samples are 
to see how much methamphetamine gets into your urine. 
§ You will complete questionnaires several times about the way you are 
feeling and about the challenge drug. The questionnaires take 
approximately five to ten minutes to complete each time.  
§ You will be asked about any changes in your health. 
§ You will be asked about any changes in your medications. 
§ You will be asked questions about your history of suicide and suicidal 
thoughts on Day 22 only unless you take part in the extended in-patient 
stay. 
 
Once all the study procedures have been completed on Day 22 and the study 
doctor thinks that you are medically stable, you will be discharged from the study 
center unless you have been asked to take part in the extended in-patient stay 
(see details below).  You will return to the study center weekly for outpatient 
visits. 
 
In-patient Extended Period (Day 22 through Day 29): 
If you are asked to stay in the study center for the extended in-patient stay, you 
will remain in the study center from Day 22 through Day 29.  You will receive the 
challenge drugs as outlined in this consent form. 
 
The following procedures will be completed: 
§ An IV catheter used for blood collection and challenge drug administration 
will be inserted into a vein.  You will have two IV catheters placed on Day 
26. 
§ Vital signs including pulse, respiration (breathing) rate, blood pressure, 
oral temperature, and pulse oximetry will be taken after you have been 
lying down for 5 minutes multiple times. 
§ ECG will be performed after you have been lying down for 5 minutes 
multiple times. 


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§ Telemetry will be monitored continuously for at least 8 hours after the 
METH Challenge dosing. 
§ A physical exam will be performed multiple times. 
§ PK blood samples (a blood sample taken to measure the amount of drug 
in your blood) will be collected approximately 19 times.  A little over ½ to 
one teaspoon of blood will be collected each time.  
§ Routine clinical laboratory tests such as blood hematology, serum 
chemistry and urinalysis will be conducted on Day 27. Approximately two 
teaspoons of blood will be collected. 
§ A blood sample to test for an immune reaction to the study drug will be 
collected on Day 28.  About one teaspoon of blood will be collected. 
§ All your urine starting just prior to the METH Challenge through 36 hours 
after dosing will be collected for urine PK samples. Urine PK samples are 
to see how much methamphetamine gets into your urine. 
§ You will complete questionnaires several times about the way you are 
feeling and about the study drug. The questionnaires take approximately 
five to ten minutes to complete each time.  
§ You will be asked questions about your history of suicide and suicidal 
thoughts on Day 29 only 
§ You will be asked about any changes in your health. 
§ You will be asked about any changes in your medications. 
 
Once all the study procedures have been completed on Day 29 and the study 
doctor thinks that you are medically stable, you will be discharged from the study 
center.  You will return to the study center weekly for outpatient visits. 
 
Outpatient Follow-up Visits (Days 28, 35, 42, 49, 56 and 63) 
You will return to the study center for weekly follow up visits after you have been 
discharged from the study center during the in-patient period.  If you participated 
in the extended in-patient period, you will not complete the Day 28 follow up visit.   
 
The following procedures will be completed at each visit: 
§ The list of prescription or non-prescription medications taken from the 
previous visit will be updated. 
§ Any changes in your health will be updated. 
§ An assessment of methamphetamine and other drug use for the past 30 
days will be done. 
§ Vital signs will be collected after you have been lying down for 5 minutes. 
Vital signs include pulse, respiration (breathing) rate, blood pressure, oral 
temperature, and pulse oximetry. 
§ A physical examination will be performed. 
§ Routine clinical laboratory tests such as blood hematology, serum 
chemistry and urinalysis will be conducted. For women, a blood sample for 
a pregnancy test will also be collected. Approximately two teaspoons of 
blood will be collected.  


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§ A PK blood sample (a blood sample taken to measure the amount of drug 
in your blood) will be collected.  About one teaspoon of blood will be 
collected.  
§ A blood sample to test for human antibody against IXT-m200, will be 
collected on Days 28 and 63.  About one teaspoon of blood will be 
collected. 
§ A urine drug screen. The results will be kept with your study chart and will 
not be discarded. 
§ An alcohol breath test. The results will be kept with your study chart and 
will not be discarded. 
 
Outpatient Follow-up Visits (Days 84 and 105) 
The following procedures will be completed at each visit: 
§ The list of prescription or non-prescription medications taken from the 
previous visit will be updated. 
§ Any changes in your health will be updated. 
§ An assessment of methamphetamine and other drug use for the past 30 
days will be done. 
§ Vital signs will be collected after you have been lying down for 5 minutes. 
Vital signs include pulse, respiration (breathing) rate, blood pressure, oral 
temperature, and pulse oximetry. 
§ A physical examination will be performed. 
§ Routine clinical laboratory tests such as blood hematology, serum 
chemistry and urinalysis will be conducted. Approximately two teaspoons 
of blood will be collected. For women, a blood sample for a pregnancy test 
will also be collected.  
§ A PK blood sample (a blood sample taken to measure the amount of drug 
in your blood) will be collected.  About one teaspoon of blood will be 
collected.  
§ A urine drug screen. The results will be kept with your study chart and will 
not be discarded. 
§ An alcohol breath test. The results will be kept with your study chart and 
will not be discarded. 
 
End-of-Study Visit (Day 126) / Early Termination Visit 
You will return to the study center for the last visit on Day 126 or in the event you 
discontinue from the study early. The following procedures will be completed: 
§ The list of prescription or non-prescription medications taken from the 
previous visit will be updated. 
§ Any changes in your health will be updated. 
§ An assessment of methamphetamine and other drug use for the past 30 
days will be done. 
§ Vital signs will be collected after you have been lying down for 5 minutes. 
Vital signs include pulse, respiration (breathing) rate, blood pressure, oral 
temperature, and pulse oximetry. 


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§ A physical examination will be performed. 
§ Routine clinical laboratory tests such as blood hematology, serum 
chemistry and urinalysis will be collected. Approximately two teaspoons of 
blood will be collected. For women, a blood sample for a pregnancy test 
will also be collected. 
§ A PK blood sample (a blood sample taken to measure the amount of drug 
in your blood) will be collected.  About one teaspoon of blood will be 
collected.  
§ A blood sample to test for an immune reaction to the study drug will be 
collected.  About one teaspoon of blood will be collected. 
§ A urine drug screen. The results will be kept with your study chart and will 
not be discarded. 
§ An alcohol breath test. The results will be kept with your study chart and 
will not be discarded. 
 
Once the above procedures have been completed, your participation in the study 
will end unless you experience a change in your health that needs to be 
monitored. 
 
Study Restrictions 
In order to be in this study, you must agree to refrain from the substances and 
activities listed in the chart below for the specified timeframes. 
 
Medication, Substance or Activity Specified Timeframe or Limit 
Strenuous 
activities, 
such 
as 
exercise or sports 
At least 72 hours prior to dosing of study 
drug and for at least 48 hours after. 
Recreational drug use 
From screening, throughout the study  
Treatment with any prescription 
medications, 
other 
than 
oral 
contraceptives, or over-the-counter 
nutritional supplements 
Within 14 days prior to the first dose of 
study drug and throughout the inpatient 
stay (until Day 22 or Day 29 if taking part 
in the extended in-patient stay). 
Any approved prescription anti-
obesity 
drug 
or 
any 
over-the-
counter medication for weight loss 
Within a period of 90 days prior to the 
first dose of study medication and 
throughout the study. 
Ingestion 
or 
use 
of 
any 
investigational medication or device 
Within 30 days prior to the first dose of 
study drug and throughout the study. 
Alcohol 
Limit consumption to approximately 1 
drink per day for women and 2 drinks per 
day for men while in the study. 1 
alcoholic drink is defined as 12 oz. beer, 
4 oz. wine, or 1 oz. distilled spirits. 
Smoking and use of tobacco-
containing products or nicotine-
Must be able to refrain from use for at 
least 3 hours on dosing days and limit 


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containing products  
use to no more than 4 cigars or pipes of 
tobacco per day or no more than 30 
cigarettes or equivalents per day. 
Blood plasma or platelets donation 
Within 30 days prior to screening and 
throughout the study 
Egg or sperm donation 
From screening until 90 days after the 
last dose of study drug(s) 
 
Roles and Responsibilities 
As a study volunteer, you will have the following responsibilities: 
§ Follow the study guidelines as instructed by the study staff and the study 
doctor. 
§ Tell the study doctor of any illnesses or injuries, side effects, or any 
problems that occur during your participation in the study. 
§ Tell the study doctor or study staff of any new medications (prescription or 
over-the-counter) that you start taking after signing this consent form. 
§ Return to the study center as instructed by the study staff.  
 
Note: You may be removed from the study because of inappropriate conduct, not 
following instructions or violation of study protocol or the study center rules.   
 
What are the potential risks of being in the study? 
 
In this study, you will receive IXT-m200, Methamphetamine HCl and placebo. 
 
IXT-m200 Risks: 
IXT-m200 is a chimeric (meaning part mouse, part human) monoclonal antibody.  
Risks of monoclonal antibodies include the following: 
§ Allergic reactions, such as hives or itching 
§ Flu-like signs and symptoms, including chills, fatigue, fever, and muscle 
aches and pains 
§ Nausea, vomiting 
§ Diarrhea 
§ Skin rashes 
§ Low blood pressure 
 
One study has been conducted with IXT-m200 in healthy male and females to 
date. In this first clinical study, of 42 participants (17 females) 32 received IXT-
m200 of doses up to 20 mg/kg and 10 participants receiving placebo (saline). 
 
There were no serious adverse events or serious adverse reactions during the 
conduct of the study. One participant had an infusion reaction halfway through 
the IXT-m200 infusion. The participant experienced a brief period of 
bronchospasm and wheezing. Bronchospasm is a sudden constriction of the 
muscles in the walls of the bronchioles (airway). The infusion was stopped, and 


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the participant was treated. No further symptoms were noted, and the participant 
required treatment for bronchitis but fully recovered after the incident.  
 
There are possible risks associated with binge use of METH (high doses of 
METH taken in a short period of time) after receiving IXT-m200. IXT-m200 may 
increase the concentration of METH in the blood or tissues when large doses of 
METH are used.  While IXT-m200 is in your system, you may react differently to 
typical doses of methamphetamine, and this reaction may change over time. It is 
possible that binge use of METH after receiving IXT-m200 could be extremely 
dangerous and possibly life-threatening. 
 
The METH risks listed below may be worse following a dose of IXT-m200 until it 
leaves your body (up to about 3 or 4 months after dosing). 
 
Methamphetamine Risks: 
Use of methamphetamine can have cardiovascular risks such as the following:  
§ Elevation of blood pressure  
§ Fast heart rate and palpitation  
§ Fatal cardiorespiratory arrest (sudden stoppage of heart’s ability to pump 
blood) has been reported, mostly in the context of abuse/misuse.  
 
Methamphetamine use can also include risks of the following: 
§ psychotic episodes for example hallucinations  
§ dizziness  
§ dysphoria (state of unease or generalized dissatisfaction with life) 
§ overstimulation  
§ euphoria 
§ insomnia 
§ tremor  
§ restlessness  
§ headache  
§ worsening of motor and phonic tics (involuntary muscles movements) and 
Tourette’s syndrome  
§ diarrhea  
§ constipation  
§ dryness of mouth  
§ unpleasant taste  
§ hives  
§ impotence and changes in libido (sexual drive) 
§ frequent or prolonged erections  
§ rhabdomyolysis (a condition in which damaged skeletal muscle breaks 
down rapidly)  
§ hair loss 
 


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Methamphetamine may impair your ability to perform potentially hazardous 
activities, such as driving a car or operating heavy machinery.  
 
Tolerance, extreme psychological dependence and severe social disability can 
develop during chronic (long-lasting) use of methamphetamine. Tolerance results 
in the need for increasing doses to maintain a desired effect.  
 
Abruptly discontinuing use of methamphetamine after prolonged use of high 
doses can result in extreme fatigue, mental depression and changes in sleep.  
Signs of chronic use of methamphetamine can cause severe skin lesions, 
insomnia, irritability, hyperactivity, and personality changes and psychosis. 
Abuse and/or misuse of methamphetamine have resulted in death. Fatal 
cardiorespiratory arrest has been reported in the context of abuse and/or misuse 
of methamphetamine. 
 
Placebo Risks: 
Placebo is an inactive substance that is unlikely to cause side effects. 
 
Allergic Reaction Risks: 
As with taking any drug, there is a risk of allergic reaction. Allergic reactions can 
be serious and/or life threatening and sometimes lead to death. Some symptoms 
of allergic reactions are rash, difficulty breathing, and wheezing, sudden drop in 
blood pressure, swelling around the mouth, throat or eyes, a fast heart rate, and 
sweating.  Seek treatment and alert the study doctor and study staff immediately 
if you have any of these symptoms. 
 
It is important that if you should feel any side effects, you tell the study staff or 
study doctor immediately. If it is an emergency or if you cannot contact the 
study staff or study doctor, you should call 911 immediately.  
 
Other Potential Risks: 
 
Blood Draw and IV Risks: 
Risks 
associated 
with 
drawing 
blood 
from 
your veins 
may 
include 
lightheadedness, pain, bruising, and bleeding at the site of needle puncture, 
inflammation of the vein, and sometimes infection. 
 
During your stay at the study center, you will have blood drawn either from a vein 
using a needle or through an IV catheter (a small plastic tube that is temporarily 
inserted into your vein with a needle).  You will also have the challenge and study 
drugs given through an IV catheter.  You may have an IV in place for several 
hours during each treatment day.  You will have about two and a half cups of 
blood drawn during the entire study. If you take part in the In-Patient Extended 
period, you will have less than three total cups of blood drawn during the entire 
study. For comparison, a standard Red Cross blood donation is equal to about 


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two cups of blood. You may need to return for additional unexpected visits or 
additional laboratory tests.  
 
During the placement of an IV catheter into a vein, you may experience pain 
and/or bruising at the site where the IV is placed and blood is taken. In the event 
the IV fails to work properly, a direct needle stick into a vein may be needed to 
obtain blood for one or more time-points. You may experience dizziness, 
lightheadedness, and/or fainting.  Localized bruising, clotting, and infections may 
occur.  Scarring damage to a vein is also possible. 
 
If you have any questions about the use, storage and destruction of samples 
collected, ask study staff. 
 
ECG Risks: 
An ECG measures how your heart is beating. The test takes a few minutes and 
is not painful. The study staff will put electrodes (sticky patches) on your skin. 
The patches might cause irritation, redness, and/or itchiness. To make the 
patches stick, you may have to have some of the hair shaved off of your skin. 
 
Blood Pressure Measurement Risks 
Temporary discomfort and bruising caused by repeated inflation of the blood 
pressure cuff may happen.  
Confidentiality Risks: 
The loss of confidentiality is a potential risk of being in this study because the 
study inclusion criteria require recreational use of METH. We will protect 
information about you and your taking part in this research study to the best of 
our ability. However, absolute confidentiality cannot be guaranteed. 
 
Unknown Risks: 
In addition to the risks already mentioned, there may be other risks that are 
unknown and can’t be predicted.  
 
If you have any side effects or concerns, you should tell the study doctor or study 
staff immediately. If you don’t tell the study doctor and/or study staff the truth 
about any side effects or concerns, you may harm yourself by being in this study. 
If it is an emergency or if you cannot contact the study staff or study 
doctor, you should call 911 immediately. 
 
Reproductive Risks: 
The effects of the study drug(s) on a fetus (unborn baby) are unknown.   
 
If you are male, you must be sterile (for example a vasectomy) or agree to use a 
condom and spermicide in addition to your female partners using an acceptable 
form of birth control (as described below) or  abstain from sexual relations 


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throughout the study. You must also agree not to donate any sperm for 90 days 
after the last dose of study drug(s). 
 
If you are female and become pregnant while in this research study, an injury 
that we don’t know about could occur to the fetus. You may not be in this study if 
you are pregnant, are trying to get pregnant or are breastfeeding.  Women will be 
tested for pregnancy during the study. In order to take part in this research study, 
if you are able to get pregnant, you should not have sexual intercourse or you 
must use a method of birth control that is acceptable to you and the study doctor 
during the study until the end-of-study follow up visit. Women who are surgically 
sterile or who have been post-menopausal for at least one year will be 
considered unable to become pregnant and do not need to use additional birth 
control.  If you become pregnant during the study, you must tell the study doctor 
immediately.  The study drug will be stopped, and your participation in the drug 
administration phases of the study will end. We will ask you to continue to 
participate in the follow-up parts of the study. 
 
Acceptable methods of birth control for this study include the following:  
• oral contraceptive pills 
• contraceptive patches  
• vaginal ring  
• diaphragm 
• sponge 
• condom with spermicide 
• hormone injection 
• intrauterine device 
• vasectomized partner     
 
If you or your partner becomes pregnant during the study you should tell the 
study doctor immediately.  Please also tell the doctor who will be taking care of 
you/your partner during the pregnancy that you took part in this research study. 
The study doctor will ask if you/your partner or your pregnancy doctor is willing to 
provide updates on the progress of the pregnancy and its outcome. You and your 
partner are not required to provide this information. If you/your partner agree, this 
information will be provided to the study sponsor for safety monitoring follow-up. 
 
You will be informed of new information relating to the study. 
All new findings discovered during the course of this study that may influence 
your decision to stay in this study will be given to you by your study doctor as 
they become available. 
 
Does being in this study provide any benefit? 
This study is for research purposes and is not designed to offer you any 
treatment.  There is no direct benefit to you for being in this study.  
 


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Are there any alternatives to participating in the study? 
No therapeutic or other health benefits will result from participating in this study, 
so your only alternative is to not participate in the study. 
 
Whom do you contact in the event of an emergency? 
If you experience an adverse event (undesirable reaction) or a study-related 
injury during the course of the study, you should immediately contact Dr. Lynn 
Webster at (801) 269-8200 or (801) 892-5151 (if during non-business hours).  
 
If you seek emergency care, or if you are hospitalized, please alert the doctor 
who is treating you that you are enrolled in a study being conducted by Dr. Lynn 
Webster.  
 
If it is an emergency or if you cannot contact the study staff or study 
doctor, you should call 911 immediately. 
 
What happens if you have a study-related injury? 
If you experience a research injury, Pharmaceutical Research Associates, Inc. 
will provide or arrange for medical treatment. For serious, related injuries, please 
call 911. For related injuries that are not serious, contact Dr. Webster at 801-269-
8200. InterveXion Therapeutics, LLC will cover the reasonable physician fees 
and medical expenses necessary for treatment of the injury that are not covered 
by your medical and hospital insurance coverage. A research injury is any 
physical injury or illness caused by your direct participation in the study. If you 
are injured by a medical treatment or procedure that you would have received 
even if you weren’t in the study, that is not considered to be a research injury. 
There are no plans to offer you any payment for such things as lost wages, 
expenses other than medical care required for a research injury, or pain and 
suffering. To help avoid injury, it is required that you follow all study directions 
provided by the study staff. You are not giving up any of your legal rights by 
signing this form. 
 
If you are treated for a research injury that is paid for by InterveXion 
Therapeutics, LLC or its representative, your name, date of birth, gender, and 
Medicare Health Insurance Claim Number or Social Security Number will be 
collected to determine your Medicare status. If you are a Medicare beneficiary, 
InterveXion Therapeutics, LLC will report the payment and information about the 
study you are in to the Centers for Medicare & Medicaid Services, in accordance 
with CMS reporting requirements. InterveXion Therapeutics, LLC will not use this 
information for any other purpose. 
 
This study involves HIV-related information. The release of any HIV-related 
information to InterveXion Therapeutics, LLC does not permit InterveXion 
Therapeutics, LLC to re-disclose such information without your consent, unless 
permitted or required to do so under applicable state law. If you receive 


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Medicare, by signing this consent, you specifically authorize InterveXion 
Therapeutics, LLC and its representatives to disclose your HIV-related health 
information to CMS for the purpose of complying with reporting requirements. 
 
By signing this consent form, you are not giving up any legal rights that you 
would otherwise have. You are not prevented from seeking to collect 
compensation for injury related to malpractice, negligence, or misconduct on the 
part of those conducting the study. 
 
Will it cost you anything to be in this study? 
There will be no cost to you for the study doctor’s time, medicines, study 
procedures, or supplies related to this study. The challenge and study drugs 
used in the study will be given to you at no cost. The sponsor, InterveXion 
Therapeutics, LLC will pay for the study doctor’s time, study procedures, and 
supplies related to this study.  
 
Will you be compensated for being in this study? 
You will be reimbursed for time and travel associated with being in this study. 
 
If you follow all instructions and complete the entire study, you will receive the 
study completion amount. If you are dropped from the study due to 
circumstances beyond your control, such as medical reasons or technical 
problems, you will be compensated based on the number of completed visits. 
 
Any missed visits or failure to meet scheduled visits will be considered non-
compliance.  If you miss a scheduled visit, you will not be eligible to receive the 
full amount stated below and you will not receive any compensation for the 
missed visit(s). 
 
If you are dropped from the study because of non-compliance or you choose to 
withdraw from the study, you will be asked to undergo the Early Termination 
procedures.  You will receive a pro-rated compensation amount based on the 
study visits that you completed. 
 
You will receive all compensation you are due within 30 days after your last 
completed visit. 
 
Visit 
Per Day 
Sub-Total 
Screening 
50.00 
50.00 
Check-in (Day -1) 
200.00 
200.00 
In-patient METH Challenge (Day 1, 5, 12 and 19) 
300.00 
1200.00 
In-patient Period (Days 2 and 3) 
200.00 
400.00 
In-patient Treatment (Day 4) 
300.00 
300.00 
In-patient Treatment Period (Days 6-11, 13-18 and 200.00 
2800.00 


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20-21)  
Discharge Treatment Period (Day 22) 
150.00 
150.00 
Follow up Visits (Days 28, 35, 42, 49, 56, 63, 84, 
105 and 126) 
150.00 
1350.00  
Completion Stipend (on Day 126) 
1100.00 
1100.00 
Total 
 
$7550.00 
 
If you take part in the extended inpatient period you will receive the additional 
compensation listed below: 
 
Extended In-patient Compensation 
Per Day 
Sub-Total 
Extended In-patient METH Challenge (Day 26) 
300.00 
300.00 
Extended In-patient Period Days 22 and 28 
50.00 
100.00 
Extended In-patient Period (Days 23-25 and Day 
27) 
200.00 
800.00 
Discharge Extended In-patient Period (Day 29) 
150.00 
150.00 
Completion Stipend (on Day 126) 
350.00 
350.00 
 
Total 
 
 
$1700.00 
 
Once you are enrolled, if the PRA medical team requires you to return to the 
clinic for additional physical examinations, blood, urine or ECG testing after you 
have completed your participation in the study, you will be compensated an 
additional amount for your time and travel; the amount will range between $50 to 
$100 depending on the procedures. 
 
Financial compensation for such things as lost wages, disability, or discomfort 
due to study-related injury is not offered. There will be no financial compensation 
for any medical expenses due to personal injury caused by you.  
 
This compensation will be considered earned income and will be reported to the 
IRS, as required by law.  You will receive a 1099 Form.  If you do not know what 
this form is, please ask the study staff.  
 
Do you have to be in this study? 
Being in this study is voluntary. This means you can decide if you do or do not 
want to be in the study. If you decide to be in the study, you can stop at any time.  
If you decide that you no longer want to be in the study, you will be asked to 
complete Early Termination procedures. 
 
You can take a copy of this consent form home with you, so you can read and 
talk about it with other people before you sign it. If you decide to be in this study, 
you will be asked to sign and date this form. You will also get a copy of the 
signed and dated form. 
 


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You can withdraw your consent to be in this study, at any time, without penalty or 
loss of benefits.   
 
If you decide to withdraw from the study and want to leave the clinic after you 
have recently taken a study drug that may cause side effects like drowsiness or 
fuzzy thinking, you will be asked to stay at PRA until it is physically safe for you 
to leave. If you insist on leaving PRA before the PRA study staff has determined 
it would be physically safe for you to leave, you will be asked to sign a separate 
Against Medical Advice Form. 
 
Can you be removed from the study without your permission? 
Your study doctor may end your participation in this study for any of the following 
reasons:   
§ If you develop a side effect or medical condition that may place you at risk 
of more complications by staying in the study or if you need a medicine 
not allowed in this study; 
§ If you become disruptive during the study; 
§ If you do not follow the study doctor’s or study staff’s instructions; 
§ If you become pregnant; 
§ If you are unable to take the doses;  
§ If you are unable to keep your scheduled appointments; 
§ If the study is cancelled by InterveXion Therapeutics, LLC, Midlands IRB 
or by the FDA; the Midlands IRB is an independent ethics committee that 
reviews the conduct of human research studies. 
§ For administrative reasons. 
 
Who will have access to your study and/or medical information? 
As part of this study, your personal and medical information will be collected, 
including the following:  
§ Your name 
§ Address 
§ Birth date  
§ Medical records 
§ Information gathered for this study 
§ Records about the study (such as drugs or treatments) 
 
In addition to the people directly involved with the study, other people may see 
your information. These people and organizations include the following: 
§ Pharmaceutical Research Associates, Inc., InterveXion Therapeutics, LLC 
and/or its representatives 
§ People hired by InterveXion Therapeutics, LLC to review the study 
information 
 
You do not have to give us permission to use and give out your information. 
However, if you do not give us this permission, you cannot be in this study. 


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All of your study data will be kept in secure location(s) and may be held and 
processed on computers. 
 
Your medical records and signed consent form may also be reviewed and 
copied. Because of the need to release information to some groups, absolute 
confidentiality cannot be guaranteed. These groups are 
§ InterveXion Therapeutics, LLC, the study sponsor 
§ Food and Drug Administration 
§ Midlands IRB 
§ Other governmental agencies, both foreign and domestic. 
Study data may be transferred to other countries for processing, including 
countries not covered by data protection legislation 
 
Although the results of this study may be presented at meetings and in 
publications, your identity will be kept private.  
 
Certificate of Confidentiality 
To help us protect your privacy, we have obtained a Certificate of Confidentiality 
from the National Institutes of Health.  With this Certificate, the study staff cannot be 
forced to disclose information that may identify you, even by a court subpoena, in 
any federal, state, or local civil, criminal, administrative, legislative, or other 
proceedings. The study staff will use the Certificate to resist any demands for 
information that would identify you, except as explained below. 
 
The Certificate cannot be used to resist a demand for information from personnel of 
the United States Government if that information is to be used for auditing or 
evaluation of federally-funded projects or for information that must be disclosed in 
order to meet the requirements of the FDA. 
 
A Certificate of Confidentiality does not prevent you or a member of your family 
from voluntarily releasing information about you or your involvement in this study. If 
an insurer, employer, or other person obtains your written consent to receive study 
information, then the study staff may not use the Certificate to withhold that 
information. 
 
The Certificate of Confidentiality does not prevent the study staff from disclosing 
voluntarily, without your consent, information that would identify you as a participant 
in the study under the following circumstances: intent to harm yourself or others 
and child abuse. 
 
 
 
 
 


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PERSONS TO CONTACT FOR QUESTIONS, CONCERNS, OR COMPLAINTS 
 
If you have any questions, concerns or complaints about this study, contact Lynn 
Webster at (801) 269-8200, Monday-Friday between 8:00 am-5:00 pm or after 
hours at (801) 892-5151.  
 
If you have questions about your rights, general questions, complaints or 
concerns about this research, or questions about your rights as a person taking 
part in this study, call the Midlands Independent Review Board (MLIRB) at (913) 
385-1414 or (800) 636-4445. If, at any time during or after your participation in 
this research, you would like information or to offer input about your research 
experience, you can call the Midlands IRB at the number above or you can go to 
the Midlands IRB website at www.mlirb.com and give us your comments.  Either 
way you do not have to give us your name, if you do not want to. 
 
You have the right to ask any questions concerning the potential and/or unknown 
hazards of this study, at any time.  If you have any questions concerning your 
participation in this study, or if at any time you feel you have experienced a 
research-related injury or a reaction to the study drug, contact Lynn Webster at 
(801) 269-8200, Monday-Friday between 8:00 am-5:00 pm or after hours at (801) 
892-5151. 
 
LEGAL RIGHTS 
You will not lose any of your legal rights to which you are otherwise entitled by 
signing this consent form. 
 
 


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SUBJECT’S STATEMENT 
CONSENT 
By signing this form you are agreeing to the following: 
 
§ That you have read this Informed Consent form or someone read it to you.  
§ This form describes the purpose and nature of this study.  
§ You have had time to review this information.  
§ You have been offered a chance to ask questions.  
§ You received satisfactory answers to your questions.  
§ If you do not take part in the study, you will not lose any benefits.  
§ If you leave the study, you will not lose any benefits. 
§ If you leave the study, you will not lose any legal rights. 
§ Your participation in this study is completely voluntary. 
  
 
You will receive a copy of this signed and dated Informed Consent Document for 
your records.  
 
You agree to participate in this study. 
 
 
__________________________________ 
______________ 
Print Participant’s Name 
  
 
Date 
 
 
__________________________________ 
 
Time Signed __ __ : __ __ 
Study Participant (signature)  
 
 
__________________________________ 
 
___________________ 
Print Name of person who explained this study  
Date 
 
 
__________________________________ 
 
Time Signed __ __ : __ __ 
Person who explained this study (signature) 
 


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AUTHORIZATION TO USE AND DISCLOSE MEDICAL INFORMATION 
 
A federal regulation known as the Privacy Rule gives you certain rights 
concerning the privacy of your health information.  The Privacy Rule was issued 
under a law called the Health Insurance Portability and Accountability Act of 1996 
(HIPAA).  Researchers covered by this rule are required to get your authorization 
(permission) to use and disclose (share with others) any health information that 
could identify you. Under this federal law, your records cannot be used or 
disclosed by Pharmaceutical Research Associates, Inc. for research purposes 
unless you sign this form.  You may not take part in this study unless you sign 
this form.   
 
If you sign this Form, you will be agreeing to the disclosures described below:   
 
This section, called an “Authorization,” explains how your health information will 
be used and disclosed and describes your rights.     
 
Your personal health information may be used or disclosed in order to conduct 
this study, as necessary for your study-related procedures or payment for such 
procedures, to allow Pharmaceutical Research Associates, Inc. to conduct its 
normal business operations, and to ensure that information related to the study is 
available to the parties that need it for research purposes. The sponsor, 
InterveXion Therapeutics, LLC, may add your information to research databases 
so that it can study better measures of safety and effectiveness, study other 
therapies for patients, develop a better understanding of disease, or improve the 
effectiveness of future clinical trials.  
 
This personal health information may include, but is not limited to, your name, 
address, telephone number, date of birth, government-issued identification 
number, and medical records and charts, including the results of all tests and 
procedures performed during the study. 
 
The study data that InterveXion Therapeutics, LLC requests does not include 
your name, address, or social security number. Instead, the study doctor uses 
your initials and assigns a code number to your records that are sent to 
InterveXion Therapeutics, LLC Your records will be assigned a code number.  
Your personal health information will be kept as confidential as possible under 
the law; however, absolute confidentiality cannot be guaranteed.   
 
Your medical records will be reviewed or copied at Pharmaceutical Research 
Associates, Inc., InterveXion Therapeutics, LLC and/or its representatives and 
may be reviewed or copied by regulatory authorities or other oversight bodies, 
including the Midlands IRB, for this study. The purpose of these reviews is to 
make sure the study is being conducted properly and that the data are being 
collected correctly, or for other purposes, allowed by law.  


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Some or all of the test results and other information will be reported to 
InterveXion Therapeutics, LLC.  InterveXion Therapeutics, LLC and its 
representatives will analyze this information.  Their findings may be reported to 
the U.S. Food and Drug Administration (the FDA) or other regulatory agencies in 
the United States and foreign countries.   
 
The Midlands IRB may also review your records.     
 
Except for the disclosures described above, they will not disclose your records to 
other parties.  Once your health data has been shared with authorized users, it 
may no longer be protected by Federal privacy law. 
 
In no event will you be identified by name in any published reports about this 
study or in any other scientific publications or presentations.  
 
You have the right to request access to your personal health information from the 
study doctor.  To ensure the scientific integrity of the study, you may not be able 
to review some of your records related to the study until after the study has been 
completed.  
 
Your study records may be kept at Pharmaceutical Research Associates, Inc. 
indefinitely following the completion of the study.  You may not have the right to 
review your records while the study is in progress.  You will be able to review 
your records after the study has been completed. 
 
This Authorization does not expire; however, you have the right to revoke this 
authorization at any time by giving written notice to the study doctor.  The study 
doctor’s and Pharmaceutical Research Associates, Inc. contact information is: 
 
Pharmaceutical Research Associates, Inc. 
1255 East 3900 South 
Salt Lake City, UT 84124 
 
If you revoke this authorization, you will not be permitted to continue in this study. 
Neither Pharmaceutical Research Associates, Inc., nor InterveXion Therapeutics, 
LLC will be able to use or disclose your personal health information from this 
study except to the extent that they have already relied on this information to 
conduct the study. 
 
Under federal law, your study records cannot be used or disclosed for research 
purposes unless you sign this authorization. You may refuse to sign this 
authorization; however, you may not take part in the study unless you sign this 
authorization.  If you revoke this authorization, you will not be able to stay in the 
study. If you drop out of the study, you do not have to revoke this authorization. If 


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you drop out and decide to revoke your authorization, the information that has 
already been collected in your study record may continue to be used and 
disclosed as described above.  If you cancel this Authorization, Pharmaceutical 
Research Associates, Inc. and InterveXion Therapeutics, LLC will no longer use 
or disclose your personal health information under the Authorization for this 
study, unless the study doctor needs to use or disclose some of your personal 
health information to preserve the scientific integrity of the study. Information 
given to InterveXion Therapeutics, LLC before you cancel this Authorization may 
still be used by InterveXion Therapeutics, LLC. No new information will be added. 
 
You have read, in a language that you understand well, the above information.  
The content and meaning of this information has been explained to you.  You 
hereby voluntarily consent and offer to take part in this study and authorize the 
use and disclosure of your medical information.   
 
You have not forfeited any of your legal rights by signing this authorization.  You 
will receive a copy of the signed and dated form. 
 
Your signature on this form will authorize (give permission for) Pharmaceutical 
Research Associates, Inc. to collect and use information that can identify you. 
 
Statement of Authorization 
I have read this form, and its contents were explained. My questions have been 
answered. I voluntarily agree to allow the study staff to collect, use and share my 
health data as specified in this form. I will receive a signed and dated copy of this 
form for my records. I am not giving up any of my legal rights by signing this 
form.  
 
 
 
 
Printed Name of Study Participant 
 
 
Signature of Study Participant 
 
Date 
 


Version 4, May 31, 2018 
M200C-1801 
Version 4 
Approved by MLIRB on 06/01/18 
Page 28 of 28 
 
  
Statement of Person Explaining Authorization 
I have carefully explained to the subject the nature and purpose of this form. I 
have been available to answer any questions that the subject has had about this 
form. 
 
 
 
 
Printed Name of Person Explaining Authorization 
 
 
Signature of Person Explaining Authorization 
 
Date 
 

SAP_002.pdf: 
Study title: 
STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy 
Protocol number: 
M200C-1801 
NCT number: 
NCT03336866 
Document date: 
07Apr2020 
 




Statistical Analysis Plan 
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Protocol: M200C-1801 
Version Date: 07-APR-2020  
EDSREP 009 T 01 G 
Page 2 of 39 
2.0 Table of Contents 
1.0 Approvals ................................................................................................................................................. 1 
2.0 Table of Contents ..................................................................................................................................... 2 
3.0 Introduction .............................................................................................................................................. 4 
4.0 Changes from Previous Version of Approved SAP ................................................................................. 4 
5.0 Study Objectives and Endpoints .............................................................................................................. 4 
5.1 Primary Objective ................................................................................................................................. 4 
5.1.1 Primary Endpoint .......................................................................................................................... 4 
5.2 Secondary Objectives .......................................................................................................................... 4 
5.2.1 Secondary Endpoints .................................................................................................................... 5 
5.3 Study Hypothesis ................................................................................................................................. 5 
6.0 Study Design ............................................................................................................................................ 5 
6.1 Sample Size Considerations ................................................................................................................ 5 
6.2 Randomization ..................................................................................................................................... 6 
7.0 Overview of Planned Analysis ................................................................................................................. 6 
7.1 Changes from Protocol ........................................................................................................................ 6 
7.2 Interim Analysis .................................................................................................................................... 6 
7.3 Inpatient Completion Analysis ............................................................................................................. 7 
7.4 Final Analysis ....................................................................................................................................... 7 
8.0 Data Review ............................................................................................................................................. 7 
8.1 Data Management ............................................................................................................................... 7 
8.2 Acceptance of Data for Summarization ............................................................................................... 7 
9.0 Definitions and General Analysis Methods .............................................................................................. 8 
9.1 Analysis Data Presentation .................................................................................................................. 8 
9.1.1 Rounding ....................................................................................................................................... 8 
9.1.2 Imputation ..................................................................................................................................... 8 
9.1.3 Daylight Savings Time Adjustments ............................................................................................. 8 
9.1.4 Descriptive Statistics ..................................................................................................................... 8 
9.1.5 Pooling .......................................................................................................................................... 8 
9.1.6 Unscheduled and Early Termination Measurements ................................................................... 9 
9.2 Analysis Data Definitions ..................................................................................................................... 9 
9.2.1 Baseline Definition ........................................................................................................................ 9 
9.2.2 Treatment/Subject Grouping......................................................................................................... 9 
9.2.3 Common Variable Derivations ...................................................................................................... 9 
9.2.4 QC ............................................................................................................................................... 10 
9.2.5 ADaM Datasets and Metadata.................................................................................................... 10 
9.3 Software ............................................................................................................................................. 10 
9.4 Statistical Methods ............................................................................................................................. 10 
9.4.1 Statistical Outlier Determination ................................................................................................. 10 
9.4.2 Predetermined Covariates and Prognostic Factors .................................................................... 10 
9.4.3 Hypothesis Testing ..................................................................................................................... 10 
9.5 TFL Layout ......................................................................................................................................... 11 
10.0 Analysis Sets ....................................................................................................................................... 11 
10.1 Qualification Safety Set ................................................................................................................... 11 
10.2 Safety Set ........................................................................................................................................ 11 
10.3 Pharmacokinetic Set ........................................................................................................................ 11 
10.4 Pharmacodynamic Set ..................................................................................................................... 11 
11.0 Subject Disposition .............................................................................................................................. 12 
12.0 Protocol Deviations and Violations ...................................................................................................... 12 
13.0 Demographic and Baseline Characteristics......................................................................................... 12 
13.1 Demographics .................................................................................................................................. 12 
13.2 Medical History ................................................................................................................................ 12 
13.3 Other Baseline Characteristics ........................................................................................................ 12 
14.0 Concomitant Medications .................................................................................................................... 12 


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15.0 Treatment Compliance and Exposure ................................................................................................. 12 
16.0 Pharmacokinetic Analyses ................................................................................................................... 13 
16.1 Pharmacokinetic Variables .............................................................................................................. 13 
16.1.1 Serum and Plasma Variables ................................................................................................... 13 
Table 1: Plasma/Serum Pharmacokinetic Parameters ................................................................................ 14 
16.1.2 Urine Variables ......................................................................................................................... 17 
Table 2: Urine Parameters ........................................................................................................................... 18 
16.2 Pharmacokinetic Summaries ........................................................................................................... 18 
16.2.1 Pharmacokinetic Concentrations .............................................................................................. 18 
16.2.2 Pharmacokinetic Parameters.................................................................................................... 19 
16.2.3 Pharmacokinetic Amounts Excreted ......................................................................................... 20 
17.0 Pharmacodynamic Analysis ................................................................................................................. 21 
17.1 Pharmacodynamic Variables ........................................................................................................... 21 
17.2 Pharmacodynamic Parameters ....................................................................................................... 22 
17.3 Pharmacodynamic Summaries ........................................................................................................ 22 
17.3.1 Pharmacodynamic Assessments ............................................................................................. 22 
17.3.2 Pharmacodynamic Parameters ................................................................................................ 22 
18.0 Safety Analyses ................................................................................................................................... 24 
18.1 Safety Variables ............................................................................................................................... 24 
18.1.1 Adverse Events ......................................................................................................................... 24 
18.1.2 Deaths and Serious Adverse Events ........................................................................................ 25 
18.1.3 Laboratory Data ........................................................................................................................ 25 
18.1.4 Vital Signs ................................................................................................................................. 25 
18.1.5 Electrocardiograms ................................................................................................................... 25 
18.1.6 Immunogenicity ......................................................................................................................... 26 
18.1.7 Other Observations Related to Safety ...................................................................................... 26 
19.0 References ........................................................................................................................................... 27 
Appendix 1: Glossary of Abbreviations ........................................................................................................ 28 
Appendix 2: Schedule of Assessments ....................................................................................................... 30 
Appendix 3: List of End of Text Outputs ...................................................................................................... 34 
Appendix 4: Shells for Post-Text Tables, Figures and Listings ................................................................... 39 
20.0 Document History ................................................................................................................................ 39 
 


Statistical Analysis Plan 
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Protocol: M200C-1801 
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3.0 Introduction 
This Statistical Analysis Plan (SAP) describes the statistical methods that will be used during the analysis 
and reporting of data collected under InterveXion Therapeutics, LLC Protocol M200C-1801. 
This SAP should be read in conjunction with the study protocol and electronic case report form (eCRF). 
This version of the plan has been developed using the protocol dated 30-MAY-2018 (including all 
amendments up to this protocol date) and the SAP has been amended to follow the amended protocol 
dated 20-AUG-2019 and the final eCRF(s) dated 09-MAR-2020. 
An approved and signed SAP is a requirement for interim analysis and database lock. An approved SAP is 
also required for unblinding of the study treatments. 
This SAP only covers the results that will be processed by the PRA Early Development Services (EDS) 
Biostatistics Department. 
PRA EDS will perform the pharmacokinetic (PK), pharmacodynamic (PD), and safety and tolerability 
evaluation.  
This SAP supersedes the statistical considerations identified in the protocol; where considerations are 
substantially different, they will be so identified. Any post-hoc or unplanned analyses, or significant changes 
from the planned analysis in this SAP performed to provide results for inclusion in the clinical study report 
(CSR) but not included in this SAP, will be clearly identified in Section 9.8.2 of the CSR. Changes to planned 
analyses do not require an updated SAP but should be included in the CSR if significant. 
4.0 Changes from Previous Version of Approved SAP 
This is the first amendment to the SAP. Changes made include: 
• 
Update to the number of subjects per dose group in Cohort 3 per Protocol Version 7.0 (10-JUL-
2019).  
• 
Update to randomization information due to the addition of Anaheim Clinical Trials site. 
• 
Documentation of the Inpatient Completion Analyses planned following first database lock, and 
Final Analyses planned following final database lock. 
• 
Updates to clarity of PK parameter handling based on diagnostic parameters 
• 
Summaries of AEs broken out by inpatient and outpatient periods based on subject discharge date 
• 
Addition of summaries of Immunogenicity 
 
5.0 Study Objectives and Endpoints 
5.1 Primary Objective 
To determine the effect of IXT-m200 on methamphetamine (METH) PK parameters relative to Placebo. 
5.1.1 Primary Endpoint 
Change in plasma METH area under the curve (AUC) and maximum concentration (Cmax) resulting from 
METH challenge doses following single intravenous (IV) doses of IXT-m200. 
5.2 Secondary Objectives 
To determine the effect of IXT-m200 on METH subjective effects. 
To evaluate the safety and tolerability and PK of a single IV dose of IXT-m200 with concomitant weekly IV 
METH challenges in subjects with METH use disorders. 


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5.2.1 Secondary Endpoints 
• 
Subjective effects of METH challenge doses as measured by the Drug Effects Questionnaire (DEQ) 
(i.e., reduction of ‘High’ or ‘Liking’). 
• 
Safety and tolerability of IXT-m200 with concomitant weekly METH challenges as measured by 
physical examinations and vital signs, adverse events (AEs), electrocardiograms (ECGs), and 
clinical laboratory testing, and immune response by measurement of anti-IXT-m200 antibody 
levels. 
• 
Pharmacokinetics of IXT-m200 following single administration. 
5.3 Study Hypothesis 
This is primarily a PK and safety study that is not evaluating any formal hypotheses. 
Primary: Treatment with IXT-m200 will increase systemic METH exposure (Cmax, AUC) following METH 
administration compared to Placebo. (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 Placebo.) 
Secondary: Treatment with IXT-m200 will decrease subjective effects of METH compared to Placebo. 
(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 Placebo) 
6.0 Study Design 
A dose run-up approach to a random-block dose assignment will be used.  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. 
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 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 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. 
6.1 Sample Size Considerations 
This is primarily a PK and safety study that is not evaluating any formal hypotheses.  


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It is planned that a targeted minimum of 10, 18, and 14 completers at the IXT-m200 6 mg/kg, 20 mg/kg, 
and Placebo 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. 
Approximately 21 subjects will be allowed to stay through the Inpatient Extension Stay for the Day 26 METH 
Challenge Day.  
6.2 Randomization 
Eleven independent double-blind randomization schedules will be prepared by PRA Health Sciences EDS, 
one for each Challenge Day for each study site (PRA Salt Lake City and Anaheim Clinical Trials, 10 total) 
and one for IXT-m200 treatment arm.  
On Day 4 of the study, each subject will be assigned a unique randomization number beginning with 1X01 
in each Cohort (where X identifies the Cohort number) that will determine the subject’s treatment arm 
according to the following allocations:  
Cohort 
Dose Assignment 
1 
(N=18) 
Randomization 2:1 (odds of Placebo = 33%) 
LOW = 6 mg/kg IXT-m200 (n=12) 
Placebo (n=6) 
2 
(N=18) 
Randomization 1:1:1 (odds of Placebo = 33%) 
LOW = 6 mg/kg IXT-m200 (n=6) 
HIGH = 20 mg/kg IXT-m200 (n=6) 
Placebo (n=6) 
3 
(N=36) 
Randomization 2:1 (odds of Placebo = 33%) 
HIGH = 20 mg/kg IXT-m200 (n=24) 
Placebo (n=12) 
4 
(N=54) 
Randomization 2:1 (odds of Placebo = 33%) 
HIGH = 20 mg/kg IXT-m200 (n=36) 
Placebo (n=18) 
 
On each Challenge Day (Day 1, 5, 12, 19 and optionally, Day 26), subjects will be assigned a unique 
randomization number to identify the Challenge Sequence of treatment with 30 mg METH (M) and Placebo 
(P): MP or PM. Randomization numbers will be assigned on Day 1 beginning with 2001, Day 5 beginning 
with 3001, Day 12 beginning with 4001, Day 19 beginning with 5001 and Day 26 beginning with 6001. 
Therefore, each Challenge Day is independent of the previous Challenge Day.  
7.0 Overview of Planned Analysis 
7.1 Changes from Protocol 
Emin and TEmin are not calculated for Drug Effects Questionnaire (DEQ) assessments. Since Drug Liking 
and Drug Disliking are each captured separately on unipolar scales, the appropriate measure for evaluating 
Liking/Disliking is Emax, with the corresponding TEmax.  
7.2 Interim Analysis 
An unblinded interim review of the data will be conducted at the completion of Cohort 2 or upon request, 
no more than two unblinded interim reviews will be conducted throughout the study.  
PK concentration data will be transferred directly to the unblinded PK Scientist for preparation of interim PK 
parameters. Summaries of interim PK parameters based on nominal time will be provided as unformatted 


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WinNonlin output to the client in a blinded format. Descriptive statistics will be used to summarize 
parameters by treatment (each IXT-m200 dose level and placebo) and challenge day. Number of subjects 
(n) and if necessary, other descriptive statistics, may be excluded to maintain the blind of individual subjects 
in the study. No formal statistical tests will be conducted. The PRA PK Scientist will be the only team 
member to have access to the unblinded PK results. No adjustments to p-values will be made as a result 
of interim review.  
A summary of treatment emergent adverse events post-IXT-m200 dosing by system organ class and 
preferred term will be provided by treatment (IXT-m200 or placebo). Preferred terms and system organ 
class categories with fewer than 1 subject per treatment group will be excluded from the summary to 
maintain the blind of individual subjects.  
Blinded safety excel listings will be provided directly from the study database. 
An unblinded summary of METH 30 mg and Placebo PD effects (pooled across all IXT-m200 dose levels) 
on each Challenge Day was conducted in October 2019 using all PD data to date. Unblinded programmers 
were assigned to unblind the PD data to the METH/Placebo treatments, and only summary results were 
provided for review by blinded team members. This analysis was conducted to aid in the determination of 
whether or not the targeted number of completers in each dose group would be sufficient for analytical 
purposes.  
7.3 Inpatient Completion Analysis 
Upon completion of the inpatient stay (through Day 22) of the final enrolled subject, database lock activities 
will commence for all visits occurring through the date of the final subject’s Day 22 visit. After database 
lock, the study will be unblinded for both METH/Placebo dosing on each Challenge Day and IXT-m200 
dosing, METH/AMP PK data, safety data available to date and PD transfers will be received and a draft of 
the tables, listings and figures will be prepared. A draft of all Tables, Figures, and Listings (TFLs) will be 
provided except those relating to the IXT-m200 PK data. Sponsor comments will be incorporated, and the 
TFLs will be preliminarily considered final.  
7.4 Final Analysis 
Upon completion of all subjects follow-up visits, the IXT-m200 PK and ADA data transfer and updated safety 
lab transfer data will be received and the remaining visits in the database will be locked. Draft TFLs (all 
TFLs will be refreshed) will be provided after final database lock. After Sponsor comments have been 
incorporated, the TFLs will be finalized and incorporated in the first draft CSR. 
8.0 Data Review 
8.1 Data Management 
Data handling and transfer will take place under the PRA Data Management Plan for the study. 
8.2 Acceptance of Data for Summarization 
Programming of analysis datasets and TFLs may be ongoing during the data management of the study. 
However, programming of analysis datasets and TFLs will be completed and quality controlled (QC’d) after 
database lock. Only quality assured (QA’d) results released by the Safety Laboratory, Bioanalytical 
Laboratory, or other external data source will be used for the programming of analysis datasets and TFLs 
for the final report. Any data values requiring investigation or corrections that are identified while 
programming the analysis datasets and TFLs will be sent to the project Data Manager. If the issue affects 
the TFLs the Programmer or Statistician who identified the issue will follow it to resolution. 


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9.0 Definitions and General Analysis Methods 
9.1 Analysis Data Presentation 
9.1.1 Rounding 
In listings, data will be presented with the same precision as the original data.  Derived data will be rounded 
for presentation purposes.  
PK parameters and PD parameters will be rounded in the derived datasets as determined by the 
pharmacokineticist and statistician, respectively, and presented as such in the listings. Each parameter will 
have a fixed number of decimals. The pharmacokineticist/statistician will follow this rule when deciding the 
number of decimals for each parameter: no decimal if data for a parameter are generally greater than or 
equal to 100; 1 decimal if data are generally between 10 and 100; 2 decimals if data are generally between 
1 and 10; 3 decimals if data are generally below 1. 
The tmax and TEmax will be reported with 2 decimals. 
For all summaries, the mean, median, 1st and 3rd Quartile (Q1 and Q3) will be presented to 1 decimal place 
greater than the data, standard deviation (SD) and standard error (SE) to 2 decimal places greater than the 
data, and the minimum (min) and maximum (max) will be presented to the same number of decimal places 
as the data. Percentages will be presented with 1 decimal. 
9.1.2 Imputation 
Unless otherwise noted, data will not be imputed. 
9.1.3 Daylight Savings Time Adjustments 
On November 4th, 2018 and November 3rd, 2019 at 2:00 am the clocks changed to 1:00 am as Daylight 
Savings Time ended. All clinic procedures for the remainder of the treatment period were moved back by 
one hour after daylight savings time ended. All duration calculations (ie, AE durations in hours, relative time 
from dosing for PK) for times post-daylight savings time adjustment that will be relative to a time prior to 
daylight savings will need to be programmatically adjusted for the hour that was gained on the mornings of 
November 4th, 2018 and November 3rd, 2019. 
On March 10th, 2019 and March 8th, 2020 at 2:00 am the clocks changed to 3:00 am for Daylight Savings 
Time. All clinic procedures for the remainder of the treatment period were moved forward by one hour after 
daylight savings time occurs. All duration calculations for times post-daylight savings time that will be 
relative to a time prior to daylight savings will need to be programmatically adjusted for the hour that was 
lost on the mornings of March 10th, 2019 and March 8th, 2020.  
9.1.4 Descriptive Statistics 
Unless otherwise indicated, continuous variables will be summarized with the following descriptive 
statistics: number of observations (n), (arithmetic) mean, SD, min, median, and max value. 
Categorical data will be summarized with frequencies and percentages. Percentages by categories will be 
based on the number of subjects exposed within a treatment. 
For categorical data the categories will be presented in the tables exactly as they appear in the CRF / 
Database.  
9.1.5 Pooling 
Summary statistics will be calculated by treatment (and timepoint, if applicable).  


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9.1.6 Unscheduled and Early Termination Measurements 
Unscheduled and early termination measurements will be included in the listings.  With the exception of 
unscheduled measurements used for baseline, unscheduled measurements will be excluded from the 
descriptive statistics and statistical analysis. 
9.2 Analysis Data Definitions 
9.2.1 Baseline Definition 
Unless otherwise stated, baseline for postdose evaluations is defined as the last observation recorded 
before the first study drug administration during the METH Challenge on Day 1. The last observation can 
be an unscheduled / repeated measurement. 
Unless otherwise stated, predose for postdose evaluations on each Challenge Day and Day 4 is defined 
as the observed predose timepoint recorded for the given visit. If a predose observation is missing in a 
given visit, then the baseline value will be used. 
9.2.2 Treatment/Subject Grouping  
Label 
Grouping 
Study Drug 
IXT-m200 or Placebo for Day 4 dosing, METH or Placebo for METH 
Challenges 
Treatment 
Day 4: 
Placebo = 0 mg/kg IXT-m200 
LOW = 6 mg/kg IXT-m200 
HIGH = 20 mg/kg IXT-m200 
 
Challenge Days: 
Placebo 
30 mg METH 
  
9.2.3 Common Variable Derivations 
Variable 
Analysis 
Dataset 
Definition/Calculation 
Note 
Change from 
Baseline/Predose 
All 
Postdose Observation minus 
Baseline/Predose Observation 
Baseline may vary. Reference 
each section of the SAP for 
specific baseline. 
 
Note: Change from Baseline for 
PD parameters is reverse (Day 1 
– Day X) as defined in Section 
17.2.  
Analysis Study 
Day (Prior to 
Dose) 
All 
Date of Measurement minus 
Dose Date 
Day 1 is first day of first dose of 
study drug (challenge drug 
METH/Placebo). 
Analysis Study 
Day (Post Dose) 
All 
Date of Measurement minus 
Dose Date +1 
Day 1 is first day of first dose of 
study drug (challenge drug 
METH/Placebo). 


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IXT-m200 Actual 
Dose (Amount) 
ADEX 
IXT-m200 dose (mg) = dose level 
(mg/kg) * baseline body weight 
(kg) * [vol. administered (mL) / 
planned vol. (mL)] 
Baseline Weight is the last 
weight measurement prior to 
dosing on Day 4 with IXT-m200 
or Placebo.  
Completed 
through Day 22 
ADSL 
Subjects will be counted as 
completers of the inpatient stay 
based on the CRF captured 
indication. 
 
Challenge Day/ 
PK Day (PKDY) 
ADPC 
For each PK profile on each 
Challenge Day (METH) and Day 
4 (IXT-m200), PK concentrations 
captured from predose through 
72 hours postdose will be 
mapped to the day of dosing.  
For example, on Day 5 24 hour 
post start of infusion (SOI) 
timepoint for IXT-m200 
concentrations, PKDY = 4, and 
on Day 8 72 hour post start of 
infusion timepoint, PKDY = 4.  
9.2.4 QC 
The analysis datasets and the TFLs will be QC’d according to the PRA EDS QC plan. 
9.2.4.1 Critical Data 
The QC plan requires datasets be classified as critical or non-critical. As the primary objective of this study 
is to characterize the PK and assess safety and tolerability the datasets considered critical are subject level, 
PK, and adverse events (ADSL, ADPC, ADPP, and ADAE). As these are related to the primary objectives, 
these datasets will be double programmed per the QC Plan. 
9.2.5 ADaM Datasets and Metadata 
The analysis datasets will be generated in accordance with Clinical Data Interchange Standard Consortium 
(CDISC) Analysis Data Model (ADaM) Version 2.1.  
ADaM compliant datasets will be delivered to the sponsor. A define.xml file version 2 with the corresponding 
metadata will be included. Analysis results metadata are excluded. 
9.3 Software 
The statistical analysis and reporting will be done using SAS® for WindowsTM Version 9.4 or higher (SAS 
Institute, Inc.). 
PK parameter calculations will primarily be done using Phoenix® WinNonlin® version 8.1 or higher 
(Pharsight, Inc.). Additional PK computations may be performed in SAS®. 
9.4 Statistical Methods 
9.4.1 Statistical Outlier Determination 
No statistical outlier analysis is planned. 
9.4.2 Predetermined Covariates and Prognostic Factors 
There are no predetermined covariates or prognostic factors. 
9.4.3 Hypothesis Testing 
No formal hypothesis testing will be done. 


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9.5 TFL Layout 
The layout of TFLs will be according to the PRA EDS standards. Table shells are provided with and 
approved as part of this SAP. Small changes to shell layout due to the nature of the data may be required 
after lock at the discretion of the PRA project statistician. The TFLs will be provided as a single document 
in Adobe PDF format (in Letter format), and as individual files for each table, figure or listing in Rich Text 
Format (.rtf). 
10.0 Analysis Sets 
Analyses 
 
Qualification 
Safety Set 
Safety Set 
PK Set 
PD Set 
Disposition 
Summaries 
 
 
 
Safety 
Assessments 
 
 
 
 
Demographic and 
Baseline 
Characteristics 
 
 
 
 
Primary Analysis 
 
 
 
PK 
Concentrations 
 
 
 
 
PK Parameters 
 
 
 
PD Values and 
Parameters 
 
 
10.1 Qualification Safety Set 
Subjects who receive at least one dose of METH on Day 1. This set will be summarized as treated and will 
be used for the disposition summaries and safety summaries prior to Day 4 dosing of IXT-m200.  
10.2 Safety Set 
The safety set will consist of subjects who receive at least one dose of IXT-m200 on Day 4. This set will be 
summarized as treated and will be used for the safety data summaries, and baseline characteristic 
summaries, and PK concentration summaries. 
10.3 Pharmacokinetic Set 
The PK set will consist of all subjects in the safety analysis set for whom at least 1 PK parameter can be 
calculated for METH or IXT-m200. This set will be summarized as treated and will be used for PK parameter 
summaries and analyses.  
10.4 Pharmacodynamic Set 
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 exclusion 
may be determined on a case-by-case basis. 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 


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completion listings prior to database lock. This set will be summarized as treated and will be used for the 
pharmacodynamic summaries and analyses.  
11.0 Subject Disposition 
The number and percentage of subjects randomized on Day 1 Challenge Day, subjects who discontinued 
prior to Day 4 randomization to treatment arm (IXT-m200 or Placebo), subjects dosed on Day 4, and 
members of each analysis set will be presented. The number and percentage of subjects who completed 
the study (per eCRF through Day 126, and per Protocol through Day 22 of the study) and withdrew from 
the study prematurely and reasons for withdrawal will be summarized.  
12.0 Protocol Deviations and Violations 
Protocol deviations/violations will be included in the CSR. 
13.0 Demographic and Baseline Characteristics 
13.1 Demographics 
All demographic data as collected during the screening visit will be listed by subject. 
Subject demographics will be summarized descriptively for all subjects by treatment. The summary will 
include the subjects’ age (in years), sex, race, ethnicity, weight (in kg), height (in cm), and BMI (in kg/m2). 
Demographics will be summarized for the safety, PK and PD sets. 
13.2 Medical History 
Medical history, categorized by preferred term according to MedDRA, will be listed by subject.  
13.3 Other Baseline Characteristics 
Recreational drug use history will be listed by subject. Instances of non-therapeutic METH use in lifetime, 
in the prior 30 days to screening and in the time between screening and Day -1 will be recorded and listed 
by subject.  
14.0 Concomitant Medications 
Concomitant medications, categorized by medication group and subgroup according to WHO Drug 
Dictionary, will be listed by subject. Medications with an end date prior to the first dose of IXT-m200 or 
Placebo on Day 4 of the study will be considered prior medications and will be noted in the listing. If a partial 
date allows a medication to be considered concomitant it will be categorized as such. 
15.0 Treatment Compliance and Exposure 
The number of subjects receiving each dose of METH and Placebo on each METH Challenge Day and 
number of subjects receiving each dose of IXT-m200 or Placebo within each cohort and overall will be 
summarized. All exposure data will be listed by subject. All drug administration data will be listed by subject. 
Actual dose of IXT-m200 administered to each subject will be calculated as:  
IXT-m200 dose (mg) = dose level (mg/kg) * body weight (kg) * [total vol. administered (mL) / planned vol. 
225 mL] 


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16.0 Pharmacokinetic Analyses  
16.1 Pharmacokinetic Variables 
16.1.1 Serum and Plasma Variables 
Challenge Days Analysis Timepoints 
• 
Plasma METH and its metabolite, amphetamine (AMP), concentrations will be collected beginning 
at predose, then at 0.0833, 0.25, 0.5, 1, 2, 4, 4.0833, 4.25, 5, 6, 8, 12, 16, 24, 36 and 72 hours 
relative to the first challenge dose on Day 1, Day 5, Day 12, Day 19 and Day 26 (as applicable).  
• 
Scheduled timepoints as collected on the CRF will be mapped to planned timepoints relative to 
METH dosing per the table below.  
o 
Relative time from dosing of METH to each timepoint will be calculated.  
o 
Deviations from planned timepoints relative to METH dosing will be calculated.  
• 
PK Day variable for each Challenge Day from predose through 72 hours after first challenge dose 
will be mapped to the Challenge Day of dosing.  
Blood Sampling Times 
Planned Timepoint Relative to METH Dosing 
Schedule Timepoint (per eCRF) 
Challenge Sequence = MP 
(i.e. First Challenge Dose 
at Time 0 is METH 30 mg) 
Challenge Sequence = PM 
(i.e. Second Challenge Dose 
at Time 4 is METH 30 mg) 
BEFORE FIRST CHALLENGE 
PREDOSE 
PREDOSE 
0.0833 HR AFTER FIRST 
CHALLENGE 
0.0833 HR POST METH 
 
0.25 HR AFTER FIRST CHALLENGE 
0.25 HR POST METH 
 
0.5 HR AFTER FIRST CHALLENGE 
0.5 HR POST METH 
 
1 HR AFTER FIRST CHALLENGE 
1 HR POST METH 
 
2 HR AFTER FIRST CHALLENGE 
2 HR POST METH 
 
4 HR AFTER FIRST CHALLENGE* 
4 HR POST METH 
 
4.0833 HR AFTER FIRST 
CHALLENGE 
4.0833 HR POST METH 
0.0833 HR POST METH 
4.25 HR AFTER FIRST CHALLENGE 
4.25 HR POST METH 
0.25 HR POST METH 
5 HR AFTER FIRST CHALLENGE 
5 HR POST METH 
1 HR POST METH 
6 HR AFTER FIRST CHALLENGE 
6 HR POST METH 
2 HR POST METH 
8 HR AFTER FIRST CHALLENGE 
8 HR POST METH 
4 HR POST METH 
12 HR AFTER FIRST CHALLENGE 
12 HR POST METH 
8 HR POST METH 
16 HR AFTER FIRST CHALLENGE 
16 HR POST METH 
12 HR POST METH 
24 HR AFTER FIRST CHALLENGE 
24 HR POST METH 
20 HR POST METH 
36 HR AFTER FIRST CHALLENGE 
36 HR POST METH 
32 HR POST METH 
72 HR AFTER FIRST CHALLENGE 
72 HR POST METH 
68 HR POST METH 
*Scheduled Timepoint 4 HR AFTER FIRST CHALLENGE reflects 0 HR relative to second challenge dose. 
 
IXT-m200 Analysis Timepoints 


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• 
Serum IXT-m200 concentrations will be measured on Day 4 at predose, 2.25, 4, 6, 12, 24 and 72 
hours post start of the infusion, and then weekly until discharge (before the first dose of the METH 
challenge on Day 12, 19 and 26, as applicable), and at each follow-up visit (Day 28, 35, 42, 49, 56, 
63, 84, 105, 126).  
• 
Relative time from dosing of IXT-m200 to each timepoint will be calculated.  
• 
Deviations from scheduled timepoints will be calculated. 
• 
PK Day variable for Day 4 predose through 72 hours post start of infusion will be mapped to Day 
4.  
• 
PK Day for all weekly and follow-up PK collections will be the day of visit.  
16.1.1.1 Concentrations  
• 
Plasma concentration of METH and amphetamine (AMP) 
• 
Serum concentration of IXT-m200  
16.1.1.2 Parameters 
• 
PK Parameters for METH and AMP on Day 1, Day 5, Day 12, Day 19 and Day 26 (as applicable) 
• 
PK Parameters for IXT-m200 following administration on Day 4 
Table 1: Plasma/Serum Pharmacokinetic Parameters 
Parameter 
Description 
Analyte/Day 
SAS Programming 
Notes 
C0 
Initial concentration. Given only for bolus IV 
models. It is equal to the first observed 
concentration value if that value occurs at the 
dose time.  
Otherwise, it is estimated by back 
extrapolating from the first two concentration 
values. 
METH on 
Day 1, Day 
5, Day 12, 
Day 19 and 
Day 26 
 
C0 from WNL 
Cmax 
Maximum concentration. Observed peak 
analyte concentration obtained directly from 
the experimental data without interpolation, 
expressed in concentration units. 
 
METH and 
AMP on Day 
1, Day 5, 
Day 12, Day 
19 and Day 
26 
 
IXT-m200 
Cmax from WNL 
Tmax 
Time to maximum concentration. First 
observed time to reach peak analyte 
concentration obtained directly from the 
experimental data without interpolation, 
expressed in time units. 
METH and 
AMP on Day 
1, Day 5, 
Day 12, Day 
19 and Day 
26 
 
IXT-m200 
Tmax from WNL 
AUC0-36 
Area under the concentration-time curve from 
time 0 to 36 hours postdose reported only for 
subjects who received METH as the first dose 
If Challenge 
Sequence = 
MP, for 
METH and 
AUC0-36 from WNL 
summary file is used 
if time deviation at 36 
hr is ≤10%.  If time 


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Parameter 
Description 
Analyte/Day 
SAS Programming 
Notes 
of the METH challenge (Challenge Sequence 
= MP). 
AUC0-36 will be calculated by WNL to the 
actual time. 
If the nominal 36 hr concentration was taken 
with a time deviation greater than 10% at 36 hr 
or was not taken and a valid λz is available, 
then the data will be extrapolated to 36 hr. 
If the nominal 36 hr concentration was taken 
with a time deviation greater than 10% or was 
not taken and a valid λz is not available, then 
AUC0-36 hr will not be calculated. 
AMP on Day 
1, Day 5, 
Day 12, Day 
19 and Day 
26 
deviation at 36 hr is 
>10% or if the 
nominal 36 hr 
concentration is 
missing, partial area 
reported as AUC0-36 
in PARM file is used 
if Rsq ≥ 0 .75. If Rsq 
< 0.75  parameter 
will be flagged for 
exclusion in 
summaries and 
analyses. 
AUC0-32 
Area under the concentration-time curve from 
time 0 to 32 hours postdose reported only for 
subjects who received METH as the second 
dose of the METH challenge (Challenge 
Sequence = PM). 
AUC0-32 will be calculated by WNL to the 
actual time. 
If the nominal 32 hr concentration was taken 
with a time deviation greater than 10% at 32 hr 
or was not taken and a valid λz is available, 
then the data will be extrapolated to 32 hr. 
If the nominal 32 hr concentration was taken 
with a time deviation greater than 10% or was 
not taken and a valid λz is not available, then 
AUC0-32 hr will not be calculated. 
If Challenge 
Sequence = 
PM, METH 
and AMP on 
Day 1, Day 
5, Day 12, 
Day 19 and 
Day 26 
AUC0-32 from WNL 
summary file is used 
if time deviation at 32 
hr is ≤10%.   
If time deviation at 
32 hr is >10% or if 
the nominal 32 hr 
concentration is 
missing, partial area 
reported as AUC0-32 
in PARM file is used 
if Rsq ≥ 0 .75. If Rsq 
< 0.75  parameter 
will be flagged for 
exclusion in 
summaries and 
analyses. 
AUClast 
Area under the concentration-time curve (time 
0 to time of last quantifiable concentration). 
METH and 
AMP on Day 
1, Day 5, 
Day 12, Day 
19 and Day 
26 
 
IXT-m200 
AUClast from WNL 
AUCinf 
Area under the concentration-time curve (time 
0 to infinity). Percent extrapolation less than or 
equal to 30% and r2 greater than or equal to 
0.75 is required to obtain a reliable AUCinf. 
METH and 
AMP on Day 
1, Day 5, 
Day 12, Day 
19 and Day 
26 
 
IXT-m200 
AUCINF_obs from 
WNL 
If Rsq < 0.75 or 
AUC_%Extrap_obs 
>30% then 
parameter will be 
flagged for exclusion 
in summaries and 
analyses.  


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Parameter 
Description 
Analyte/Day 
SAS Programming 
Notes 
%AUCext  
(listed only) 
Percentage of the AUCinf that is due to the 
extrapolation to infinity.  
METH and 
AMP on Day 
1, Day 5, 
Day 12, Day 
19 and Day 
26 
 
IXT-m200 
AUC_%Extrap_obs 
from WNL.  
Lz (λz)      
(listed only) 
Terminal phase rate constant calculated by 
linear regression of the terminal log-linear 
portion of the concentration vs. time curve. 
Linear regression of at least three points and 
an r2 greater than or equal to 0.75 are required 
to obtain a reliable λz. 
METH and 
AMP on Day 
1, Day 5, 
Day 12, Day 
19 and Day 
26 
 
IXT-m200 
Lambda_z from WNL 
If Rsq < 0.75 then 
parameter will be 
flagged for exclusion 
in summary tables. 
t1/2 
Terminal phase half-life expressed in time 
units. r2 greater than or equal to 0.75 is 
required to obtain a reliable t1/2. 
METH and 
AMP on Day 
1, Day 5, 
Day 12, Day 
19 and Day 
26 
 
IXT-m200 
HL_Lambda_z from 
WNL 
If Rsq < 0.75 then 
parameter will be 
flagged for exclusion 
in summary tables. 
CL 
Apparent clearance. Percent extrapolation 
less than or equal to 30% and r2 greater than 
or equal to 0.75 is required to obtain a reliable 
CL.  
METH on 
Day 1, Day 
5, Day 12, 
Day 19 and 
Day 26 
 
IXT-m200 
CL_obs  for METH 
and IXT-m200 from 
WNL. 
If Rsq < 0.75 or 
AUC_%Extrap_obs > 
30% then parameter 
will be flagged for 
exclusion in 
summary tables. 
Vd 
Volume of distribution. Percent extrapolation 
less than or equal to 30% and r2 greater than 
or equal to 0.75 is required to obtain a reliable 
Vd.  
METH on 
Day 1, Day 
5, Day 12, 
Day 19 and 
Day 26 
 
IXT-m200 
Vz_obs for METH 
and IXT-m200 for 
AMP from WNL. 
If Rsq < 0.75 or 
AUC_%Extrap_obs > 
30% then parameter 
will be flagged for 
exclusion in 
summary tables. 
Rsq (listed 
only) 
Goodness of fit statistic for the log-linear 
terminal elimination phase of the 
concentration-time profile identified by least-
squares linear regression. 
METH and 
AMP on Day 
1, Day 5, 
Day 12, Day 
Rsq from WNL 
 
 


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Parameter 
Description 
Analyte/Day 
SAS Programming 
Notes 
19 and Day 
26 
 
IXT-m200 
Note: AUCs will be calculated using linear up / log down, expressed in units of concentration x time. 
16.1.2 Urine Variables 
Challenge Days Analysis Timepoints 
• 
Urine will be collected beginning at predose, then for 0-4, 4-8, 8-12, 12-16, 16-24 and 24-36 hours 
relative to the first challenge dose on Day 1, Day 5, Day 12, Day 19 and Day 26 (as applicable).  
• 
Scheduled timepoints as collected on the CRF will be mapped to planned timepoints relative to 
METH dosing per the table below.  
• 
PK Day variable for each Challenge Day from predose through 36 hours after first challenge dose 
will be mapped to the Challenge Day of dosing.  
Urine Sampling Times 
Planned Timepoint Relative to METH Dosing 
Schedule Timepoint (per eCRF) 
Challenge Sequence = MP 
(i.e. First Challenge Dose at 
Time 0 is METH 30 mg) 
Challenge Sequence = PM 
(i.e. Second Challenge 
Dose at Time 4 is METH 30 
mg) 
Predose 
PREDOSE 
PREDOSE 
0-4 
0-4 
 
4-8 
4-8 
0-4 
8-12 
8-12 
4-8 
12-16 
12-16 
8-12 
16-24 
16-24 
12-20 
24-36 
24-36 
20-32 
16.1.2.1 Amounts Excreted 
• 
Amount of METH and AMP excreted in urine (Ae) 
o 
Calculated as the urine volume times the urine concentration for each interval. 
 
 
 
 
 
 
 
 
 
 
 
 


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16.1.2.2 Parameters 
• 
PK Parameters for METH and AMP on Day 1, Day 5, Day 12, Day 19 and Day 26 
Table 2: Urine Parameters 
Parameter 
Description 
Analyte/Day 
SAS Programming 
Notes 
Ct1-t2 
Concentration (of the unchanged 
drug) in the collection interval t1-
t2.  
METH and AMP on 
Day 1, Day 5, Day 
12, Day 19 and Day 
26 
Directly from data, no 
calculation required.  
Vt1-t2 
Volume of the urine collected in 
the interval t1-t2 
METH and AMP on 
Day 1, Day 5, Day 
12, Day 19 and Day 
26 
Measured in the clinic, 
captured on the CRF, 
no calculation required.  
Aet1-t2 (urine)  
Amount of drug excreted 
unchanged into urine to time t2, 
calculated as the urine volume 
times the urine concentration for 
each interval. 
Intervals: 0-4, 4-8, 8-12, 12-16 
(challenge sequence = MP only), 
16-24 (challenge sequence = MP 
only),  12-20 (challenge sequence 
= PM only), 24-36 (challenge 
sequence = MP only),  20-32 
hours (challenge sequence = PM 
only) 
METH and AMP on 
Day 1, Day 5, Day 
12, Day 19 and Day 
26 
Concentration(t1-t2) 
*volume(t1-t2)  
Aet (urine) 
 
Ae36 and 
Ae32, 
separately 
Total amount of drug excreted 
unchanged into urine to time t (t = 
36 or 32 hours if challenge 
sequence = MP or PM, 
respectively), obtained by adding 
the amounts excreted over each 
collection interval through 36 
hours post first dose of the METH 
challenge. 
METH and AMP on 
Day 1, Day 5, Day 
12, Day 19 and Day 
26 
Summation of intervals 
[Aet1-t2] through 36 or 
32 hours post METH.  
CLr (urine) 
Renal clearance.  
 
Note: Convert units of AUC to 
units of Aet prior to calculation.  
METH and AMP on 
Day 1, Day 5, Day 
12, Day 19 and Day 
26 
CLr = Aet/AUC0-t 
where t will be 32 hr if 
Challenge Sequence = 
PM, 36 hr if Challenge 
Sequence = MP.   
 
16.2 Pharmacokinetic Summaries 
16.2.1 Pharmacokinetic Concentrations 
Concentrations for METH, AMP and IXT-m200 below the quantifiable limit (BQL) will be set to 0 in the 
computation of mean concentration values. Descriptive statistics (n, mean, geometric mean, SD, SE, 
coefficient of variation [%CV], median, min, and max) will be used to summarize the serum concentrations 


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by METH Challenge Day (as applicable) and IXT-m200 dose level at each scheduled timepoint. If over half 
of the subjects for a given timepoint have values BQL then the descriptive statistics will not be presented 
and will instead display as BQL for the mean and minimum. With the exception of max all other statistics 
will be missing. 
Linear and semi-logarithmic plots of the following profiles will be provided: 
• 
Mean plasma METH and AMP concentration by nominal sampling time relative to METH 
dosing will be provided by Challenge Day for each IXT-m200 dose level (one plot per dose 
level). 
• 
Mean plasma METH and AMP concentration by nominal sampling time relative to METH 
dosing will be provided by IXT-m200 dose level for each Challenge Day (one plot per 
Challenge Day). 
• 
Mean serum IXT-m200 concentration by nominal sampling time post IXT-m200 dosing on 
Day 4 will be provided by IXT-m200 dose level.  
These plots will show time in hours. The plots will match the summary table results and will not have an 
observation at a given timepoint if more than half of the subjects have values BQL. 
Linear and semi-logarithmic plots of the following individual concentration profiles will be provided:  
• 
Individual plasma METH and AMP concentration by actual sampling time relative to METH dosing 
will be provided by Challenge Day for each subject (one subject per page).  
• 
Individual serum IXT-m200 concentration by actual sampling time will be provided for each subject 
(one subject per page).  
These plots will show time in hours. Individual plots will use the BQL handling procedure described below 
for “Pharmacokinetic Parameters”. 
Scatter plots of individual values and mean Cmax and AUC will be provided by Challenge Day and IXT-
m200 dose level.  
All individual subject concentration data will be listed with both scheduled timepoints and timepoints relative 
to METH dosing. 
16.2.2 Pharmacokinetic Parameters 
PK parameters for METH and IXT-m200 will be estimated using non-compartmental methods with 
WinNonlin®. 
The serum/plasma PK parameters will be estimated from the concentration-time profiles. In estimating the 
PK parameters for IXT-m200, METH, and AMP, BQL values at the beginning of the profile will be set to 
zero. For IXT-m200, METH, and AMP, BQL values that occur after the first quantifiable point will be 
considered missing. Values that are embedded between BQLs, or quantifiable values occurring after two 
or more BQLs, will be set to missing at the discretion of the pharmacokineticist. To estimate the PK 
parameters for METH (METH administered via IV Bolus), concentrations that are BQL at predose or the 
beginning of the profile will be flagged for exclusion (assigned a value of missing) so that the initial 
concentration may be estimated.  Actual sampling times (relative to METH dosing for METH and AMP 
parameters), rather than scheduled sampling times, will be used in all computations involving sampling 
times. If the actual time or dose time is missing, the scheduled time (relative to METH dosing for METH and 
AMP parameters) may be substituted in order to calculate the PK parameter. 
Descriptive statistics (n, mean, geometric mean, SD, SE, %CV, median, min, and max) will be used to 
summarize the calculated PK parameters by IXT-m200 dose level and Challenge Day (as applicable). Only 
n, min, median, and max will be reported for tmax. 
Determination of points to be included in λz range will follow the Guideline for Defining, Calculating and 
Summarizing Pharmacokinetic / Pharmacodynamic Parameters (EDSREP 009 R 01). 


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16.2.2.1 Analysis of the Primary Efficacy Endpoint 
The effect of IXT-m200 on METH exposure will be evaluated with a linear mixed effects model. The 
response variable in the model will be the natural-log transformed change in METH exposure parameters: 
Cmax and AUCinf. The model will contain fixed effects for treatment, day (categorical day postdose), 
natural-log transformed Day 1 baseline parameter and a treatment-by-day interaction, and a random effect 
for subject.  
Geometric LS Mean change from Day 1 for each treatment on each day will be presented. Geometric LS 
Means Ratios of change in METH exposure for each dose level of IXT-m200 compared to Placebo on each 
Day 5 (primary), Day 12, Day 19 and Day 26 will be presented along with the 95% confidence intervals.  
The following SAS pseudo-code may be used: 
Proc mixed data=params; 
by param; 
class treatment day subject;  
model lnparmchg = treat day lnbase treatment*day/s ddfm=betwithin; 
repeated day /type=ar(1) subjectID=subject; 
lsmeans treatment*day/pdiff;  
run;  
 
16.2.3 Pharmacokinetic Amounts Excreted 
Descriptive statistics (n, arithmetic mean, geometric mean, SD, SE, %CV, median, min, and max) will be 
used to summarize the urine amounts excreted for METH and AMP by treatment at each nominal time 
interval.  
All individual subject urine concentration data, volume data and parameters will be listed. 
 
 


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17.0 Pharmacodynamic Analysis 
Subjective effects of METH will be measured by the Drug Effects VAS which will be administered within 30 
minutes prior to the first dose, then 15, 30, 45, 60, 90, 120, and 180 minutes relative to each challenge 
(METH and Placebo) on each Challenge Day. Overall Drug Liking and Take Drug Again VAS will be 
measured at 180 minutes relative to each challenge.  
17.1 Pharmacodynamic Variables 
Assessment 
Scale 
Timepoints 
Parameters to include in ADPDP 
Notes 
Balance Effects VAS 
Overall Drug 
Liking  
Bipolar 
180 min post 
challenge 
180 min Score, Change from 
Baseline Score 
 
Take Drug 
Again 
Bipolar 
180 min post 
challenge 
180 min Score, Change from 
Baseline Score 
 
Drug Effects (positive, negative, craving) 
VAS 
Predose timepoint will not be used for calculation of 
AUEC for all below VAS assessments. Instead a time 
0 value of 0 will be assumed for calculation purposes 
only. 
Feel 
Unipolar 
0 to 180 min 
post challenge 
Emax, TEmax, AUEC and Change 
from Baseline Parameters 
 
High 
Unipolar 
0 to 180 min 
post challenge 
Emax, TEmax, AUEC and Change 
from Baseline Parameters 
 
Good Effects 
Unipolar 
0 to 180 min 
post challenge 
Emax, TEmax, AUEC and Change 
from Baseline Parameters 
 
Stimulated  
Unipolar 
0 to 180 min 
post challenge 
Emax, TEmax, AUEC and Change 
from Baseline Parameters 
 
Dislike 
Unipolar 
0 to 180 min 
post challenge 
Emax, TEmax, AUEC and Change 
from Baseline Parameters 
 
Like 
Unipolar 
0 to 180 min 
post challenge 
Emax, TEmax, AUEC and Change 
from Baseline Parameters 
 
More 
Unipolar 
0 to 180 min 
post challenge 
Emax, TEmax, AUEC and Change 
from Baseline Parameters 
 
Crave 
Unipolar 
0 to 180 min 
post challenge 
Emax, TEmax, AUEC and Change 
from Baseline Parameters 
 
Note: Baseline for Change from Baseline parameters is defined as the parameter calculated on Day 1.  
 
 
 


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17.2 Pharmacodynamic Parameters 
PD parameters described below will be calculated for each VAS presented above for each subject for each 
treatment (METH and Placebo) on each Challenge Day (Day 1, 5, 12, 19, and 26). Actual assessment 
times will be used for calculation, if an actual time is missing, nominal time post challenge may be 
substituted for calculation of parameters.  
Parameter 
Description 
SAS Programming 
Notes  
Emax 
Peak (maximum) effect postdose obtained 
directly from experimental data without 
interpolation over the 180 minutes of collection.   
Maximum value post 
dose through sampling 
period.   
TEmax 
Time to peak effect. First observed time to 
reach peak effect obtained directly from the 
experimental data without interpolation, 
expressed in time units. 
Time of Emax. 
AUEC 
Area under the effect curve from time 0 to 180 
minutes post drug administration. Note, time 0 
value of 0 will be assumed for calculation of 0 to 
180 min.  
 
Measured “predose” values will not be used for 
calculation of AUEC as Drug Effects should not 
be evaluated prior to dosing.   
AUEC from SAS using 
the trapezoidal rule. 
 
1. Assume a time 0 
value of 0 for all 
unipolar scales. 
2. Calculate via 
trapezoidal rule 
from time 0 to X 
hours post dose. 
Change from Baseline 
Emax, Change from 
Baseline AUEC, 
Change from Baseline 
180 min Score 
Change from Baseline for each Emax,  AUEC 
and 180 min Score will be calculated for each 
VAS assessment for METH and Placebo on 
each Challenge Day 5, 12, 19 and 26. Baseline 
parameters are the Day 1 parameters from 
METH and Placebo, respectively.  
Challenge Day 1 
Parameter – Challenge 
Day X Parameter 
17.3 Pharmacodynamic Summaries 
17.3.1 Pharmacodynamic Assessments 
Individual subject PD assessment results collected over time will be presented in data listings for each 
treatment on each Challenge Day.  
PD assessment results collected over time will be summarized for each assessment by treatment and 
nominal timepoint on each Challenge Day using descriptive statistics (n, mean, median, SD, SE, Q1, Q3, 
min and max). 
17.3.2 Pharmacodynamic Parameters 
All PD parameters calculated will be presented in the data listings.  
PD parameters and change from baseline parameters will be summarized by challenge (METH or Placebo), 
IXT-m200 dose level and Challenge Day using descriptive statistics (n, mean, median, SD, SE, Q1, Q3, 
min and max).  


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17.3.2.1 Statistical Analysis of Pharmacodynamic Parameters 
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 parameters. The analysis will compare the change from baseline values 
for METH between each dose level of IXT-m200 and Placebo. Mean, mean differences and corresponding 
95% CIs of the mean differences will be reported.  
The following SAS pseudo-code may be used: 
proc ttest data=parm alpha=0.05; 
by test param; 
class IXTtreatment; 
var change; 
run; 
 
 


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18.0 Safety Analyses  
18.1 Safety Variables 
The following safety variables will be summarized for the Safety Set: 
• 
Adverse Events (AEs) 
• 
Clinical Laboratory Evaluations 
o 
Cytokines 
o 
Clinical Chemistry – including Liver Function Tests 
o 
Hematology 
o 
Urinalysis 
• 
Vital Signs 
o 
Supine Blood Pressure  
 
Systolic Blood Pressure 
 
Diastolic Blood Pressure  
o 
Pulse rate 
o 
Oral body temperature 
o 
Respiratory rate 
o 
Oxygen Saturation (SpO2) 
• 
Electrocardiograms (ECG) 
o 
Heart Rate 
o 
PR Interval 
o 
QRS-Duration 
o 
QT Interval 
o 
QTc (Frederica) Interval 
o 
ECG Evaluation 
• 
Immunogenicity  
 
All safety variables will be listed by subject for all subjects.  
18.1.1 Adverse Events 
All AE summaries will include only treatment emergent adverse events, unless otherwise noted. Treatment-
emergent adverse events (TEAE) are those which occur after the first dose of study drug (METH or 
Placebo) on Day 1 of the study.  
TEAEs occurring after first dose of study drug on Day 1 and prior to dosing of IXT-m200 on Day 4 will be 
summarized overall for the Qualification Safety Set. TEAEs occurring post IXT-m200 dosing on Day 4 
through the end of inpatient stay and those occurring during outpatient follow-up visits will be summarized 
separately by IXT-m200 dose level and overall for the Safety Set. Each subject’s inpatient stay ends on the 
date in which they are discharged from the clinic. Inpatient Discharge date is unique for each subject and 
is captured on the CRF as the date in which the subject was discharged from the initial clinic stay. 
A breakdown of the number and percentage of subjects reporting each TEAE, categorized by body system 
and preferred term coded according to the Medical Dictionary for Regulatory Activities (MedDRA), will be 
presented. Counting will be done by subject only, not by event; subjects will only be counted once within 
each body system or preferred term. 
Summaries of events reported, categorized by relationship to IXT-m200 and METH, will be provided. 
Subjects with multiple events within a particular body system or preferred term will be counted under the 
category of their most drug-related event within that body system or preferred term. Relationship to IXT-
m200 and METH is categorized as recorded on the eCRF (or map eCRF categories to related / unrelated). 
A summary of events reported, categorized by severity as recorded on eCRF, will also be provided. 
Subjects with multiple events within a particular body system or preferred term will be counted under the 
category of their most severe event within that body system or preferred term. 


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A listing of adverse events leading to study discontinuation will be provided. 
All AEs (including non-treatment-emergent events) recorded on the eCRF will be listed. 
The following missing data will be imputed as defined (for calculations only / will not be presented): 
• 
Missing AE start and / or end times for the calculation of onset and duration will be assumed to be 
at 00:01 for a start time and 23:59 for end times 
• 
Missing AE severity or relationship will be assumed to be severe or related, respectively 
• 
Missing AE start times for the determination of treatment emergence will be assumed to occur after 
treatment unless partial date documents the AE as happening prior to treatment 
• 
Missing AE start times for the determination of treatment assignment will be assumed to occur after 
treatment on the recorded date one minute after dosing 
• 
Missing AE start date will be assumed to be after treatment for the determination of TEAE and on 
treatment for single treatment studies but will not be attributed to treatment in studies with multiple 
treatments 
18.1.2 Deaths and Serious Adverse Events 
A listing of deaths and other serious adverse events (SAE) will be provided by subject. 
18.1.3 Laboratory Data 
Clinical laboratory data will be presented using units from the study data tabulation model (SDTM) 
Controlled Terminology. 
All laboratory data will be listed, including laboratory variables not listed in the protocol. A separate listing, 
including out-of-range values will also be provided. Normal ranges will be used directly from the clinical 
laboratory.  
Descriptive statistics summarizing continuous laboratory results for clinical chemistry, hematology and 
urinalysis (observed values and derived changes from baseline) by IXT-m200 dose level and visit will be 
included. Baseline for laboratory results is defined as the last measurement prior to first dose of study drug.  
Descriptive statistics summarizing continuous laboratory results of cytokine tests (observed and derived 
changes from predose) by treatment and scheduled time will be included. If the predose observation is 
missing, and a baseline observation exists for cytokine tests, baseline may be used.  
18.1.4 Vital Signs 
Descriptive statistics will be used to summarize vital signs and changes from predose on each METH 
Challenge Day by IXT-m200 dose level, METH Challenge Sequence (MP or PM) and scheduled time. 
Descriptive statistics will be provided to summarize vital signs and change from baseline by IXT-m200 dose 
level and scheduled time on Day 4 during and post infusion, and through each follow-up visit.  Baseline for 
vital signs is defined as the last measurement prior to first dose of study drug (prior to dosing during 
Challenge Day 1). 
All vital signs measures (including body weight) will be listed by subject.  
18.1.5 Electrocardiograms 
Descriptive statistics will be used to summarize ECG parameters (observed values and derived changes 
from predose) on each METH Challenge Day by IXT-m200 dose level, METH Challenge sequence and 
scheduled time.  
Descriptive statistics will be provided to summarize ECG parameters (observed values and derived 
changes from baseline) by IXT-m200 dose level and scheduled time on Day 4 during and post infusion. 
Baseline for ECG parameters is defined as the last measurement prior to first dose of study drug (prior to 
dosing during Challenge Day 1). 
All ECG parameters will be listed by subject.  


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Page 26 of 39 
18.1.6 Immunogenicity  
Blood samples for measurement of HACA will be taken on Days 3 (baseline), 28, 63, and 126. Results from 
baseline and the last measurement postdose will be summarized by IXT-m200 treatment group and listed 
by subject.  
18.1.7 Other Observations Related to Safety 
Physical examination findings will be listed by subject and visit.  
Drug and Alcohol screen results conducted throughout the study will be listed by subject.  
Columbia-Suicide Severity Rating Scale (C-SSRS) responses will be listed by subject.  
 
Administration of meals and snacks by study day will be listed by subject.  
 
 


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Page 27 of 39 
19.0 References 
SAS Institute, Inc., SAS® Version 9.4 software, Cary, NC. 
Clinical Study Protocol. STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy. Version 
5.0, Final, 30 May 2018. 
Clinical Study Protocol. STAMPOUT: Study of Antibody for Methamphetamine Outpatient Therapy. Version 
9.0, Final, 20 Aug 2019. 
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. 
 
 


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Version Date: 07-APR-2020  
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Page 28 of 39 
Appendix 1: Glossary of Abbreviations 
Glossary of Abbreviations: 
AE 
Adverse event 
ADaM 
Analysis data model 
AMP 
amphetamine 
AUC 
area under the concentration-time curve 
AUEC 
Area under the effect curve 
BMI 
Body mass index 
BQL 
Below the quantifiable limit 
CDISC 
Clinical Data Interchange Standard Consortium 
CI 
Confidence interval 
CSR 
Clinical study report 
CV 
Coefficient of variation 
DDT 
Data definition table 
DEQ 
Drug effects questionnaire 
DSMB 
Data and Safety Monitoring Board 
DSM-V or –IV 
Diagnostic and Statistical Manual of Mental Disorders 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDS 
Early Development Services 
HACA  
human anti-chimeric antibody 
ICF 
Informed consent form 
ICH 
The International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use 
IV 
intravenous 
LLOQ 
Lower limit of quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
METH 
methamphetamine 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
QA’d 
Quality assured 
QC’d 
Quality controlled 
SAP 
Statistical analysis plan 
SAE 
Serious adverse event 
SD 
Standard deviation 


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Version Date: 07-APR-2020  
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Glossary of Abbreviations: 
SDTM 
Study data tabulation model 
SE 
Standard error 
TEAE 
Treatment-emergent adverse event 
TFL(s) 
Tables, figures and listings 
WHO-DDE 
World Health Organization – Drug Dictionary Enhanced 
WNL 
WinNonlin 
 


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Appendix 2: Schedule of Assessments 
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 
Error! Reference source not found.).. During follow-ups, drug use history will be collected on Days 
28, 63, and 105 only. 
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). 
c. Physical exams will be done once per day. 
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. 
e. Clinical laboratory assessments will be done once per day. 
f. 
Qualitative urine drug and breath alcohol tests will be. 
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 
 
 
Inpatient Timeline (Days) 
Follow-up (Days) 
 
Screening 
-1 
1 
2 
3 
4 
5, 
12, 
19 
6, 
13, 
20 
22
p 
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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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. 
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 timepoint. Telemetry will be monitored as it is 
recorded, and a physician will review the data after completion of the recording. 
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. 
k. IXT-m200 will be administered as a 2-hour IV infusion. 
l. 
Serial blood samples will be taken for assessment of IXT-m200 and METH. 
• 
Pharmacokinetic samples for IXT-m200 will be taken predose, then 2.25, 4, 6, 12, 24, and 72 
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, 0.0833, 0.25, 0.5, 1, 2, 4, 4.0833, 4.25, 5, 
6, 8, 12, 16, 24, 36, and 72 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 
timepoint). 
m. Blood samples for measurement of HACA will be taken on Days 3 (baseline), 28, 63, and 126; 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. 
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. 
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. 
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. 
 
 
 
 
 


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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. 
c. Physical exams will be done once per day as described. 
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. 
e. Clinical laboratory assessments will be done once per day. 
f. 
Qualitative urine drug and breath alcohol tests will be performed. 
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. 
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 timepoint. Telemetry will be 
monitored as it is recorded, and a physician will review the data after completion of the recording. 
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. 
k. Serial blood samples will be taken for assessment of IXT-m200 and METH PK. 
• 
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, 0.0833, 0.25, 0.5, 1, 2, 4, 4.0833, 4.25, 5, 
6, 8, 12, 16, 24, 36, and 72 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 
timepoint). 
l. 
Blood samples for measurement of HACA will be taken on Days 28, 63, and 126; if a sample is 
missed, it should be collected at the next visit. 
 
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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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. 
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.


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Appendix 3: List of End of Text Outputs 
List of End of Text Tables and Figures: 
Output 
Title  
Population 
Set 
Final 
Analysis 
Only 
Section 14.1 – Disposition and Demographic Data 
 
Table 14.1.1.1 
Summary of Subject Disposition – Screening and 
Qualification 
All Subjects 
 
Table 14.1.1.2 
Summary of Subject Disposition 
Safety 
 
Table 14.1.2.1 
Summary of Demographics 
Safety 
 
Table 14.1.2.2 
Summary of Demographics 
PK 
 
Table 14.1.3.1 
Summary of Qualification Study Drug Administration  
Qualification 
Safety 
 
Table 14.1.3.2 
Summary of Study Drug Administration – METH 
Challenges of  
Safety 
 
Table 14.1.3.3 
Summary of Study Drug Administration – IXT-m200 
Safety 
 
Section 14.2.1 – Pharmacokinetic Data 
 
Table 14.2.1.1.1 
Summary of METH and AMP Plasma Concentrations 
by Challenge Day 
Safety 
 
Table 14.2.1.1.2 
Summary of METH and AMP Pharmacokinetic 
Parameters by Challenge Day 
PK 
 
Table 14.2.1.1.3 
Statistical Analysis of Change in METH 
Pharmacokinetic Parameters following IXT-m200 
Dosing 
PK 
 
Table 14.2.1.2 
Summary of METH and AMP Urine Pharmacokinetic 
Parameters by Challenge Day 
PK 
 
Table 14.2.1.3.1 
Summary IXT-m200 Serum Concentrations 
Safety 
Only at 
Final Lock 
Table 14.2.1.3.2 
Summary IXT-m200 Pharmacokinetic Parameters 
PK 
Only at 
Final Lock 
Figure 14.2.1.4.1 
Plot of Mean METH and AMP Plasma Concentrations 
versus Time on a Linear Scale by Challenge Day for 
each IXT-m200 Dose Level 
Safety 
 
Figure 14.2.1.4.2 
Plot of Mean METH and AMP Plasma Concentrations 
versus Time on a Linear Scale by IXT-m200 Dose 
Level for each Challenge Day 
Safety 
 
Figure 14.2. 
2.4.3 
Plot of Mean METH and AMP Plasma Concentrations 
versus Time on a Semi-Log Scale by Challenge Day 
for each IXT-m200 Dose Level 
Safety 
 


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Figure 14.2.1.4.4 
Plot of Mean METH and AMP Plasma Concentrations 
versus Time on a Semi-Log Scale by IXT-m200 Dose 
Level for each Challenge Day 
Safety 
 
Figure 14.2.1.4.5 
Plot of Individual METH and AMP Plasma 
Concentrations versus Time on a Linear Scale by 
Challenge Day 
Safety 
 
Figure 14.2.1.4.6 
Plot of Individual METH and AMP Plasma 
Concentrations versus Time on a Semi-Log Scale by 
Challenge Day 
Safety 
 
Figure 14.2.1.4.7 
Scatter Plot of METH Plasma Pharmacokinetic 
Parameters by Challenge Day for each Treatment 
PK 
 
Figure 14.2.1.4.8 
Scatter Plot of METH Plasma Pharmacokinetic 
Parameters by Treatment for each Challenge Day 
PK 
 
Figure 14.2.1.5.1 
Plot of Mean IXT-m200 Serum Concentrations versus 
Time on a Linear Scale 
Safety 
Only at 
Final Lock 
Figure 14.2.1.5.2 
Plot of Mean IXT-m200 Serum Concentrations versus 
Time on a Semi-Log Scale 
Safety 
Only at 
Final Lock 
Figure 14.2.1.5.3 
Plot of Individual IXT-m200 Serum Concentrations 
versus Time on a Linear Scale 
Safety 
Only at 
Final Lock 
Figure 14.2.1.5.4 
Plot of Individual IXT-m200 Serum Concentrations 
versus Time on a Semi-Log Scale 
Safety 
Only at 
Final Lock 
Section 14.2.2 – Pharmacodynamic Data 
 
Table 14.2.2.1 
Summary of Subjective Effects Questionnaires by 
Challenge Day 
PD 
 
Table 14.2.2.2 
Summary of Subjective Effects Parameters and 
Change from Baseline by Challenge Day 
PD 
 
Table 14.2.2.3 
Statistical Analysis of Change from Baseline 
Subjective Effects Parameters by Challenge Day 
PD 
 
Section 14.3 – Safety Data 
 
Table 14.3.1.1.1 
Summary of Adverse Events Occurring Prior to IXT-
m200 Dosing on Day 4 
Qualification 
Safety 
 
Table 14.3.1.1.2 
Summary of Adverse Events Occurring During 
Inpatient Stay After IXT-m200 Dosing on Day 4 
Safety 
 
Table 14.3.1.1.3 
Summary of Adverse Events Occurring During 
Outpatient Follow-up 
Safety 
 
Table 14.3.1.2.1 
Summary of Treatment Emergent Adverse Events 
Occurring Prior to IXT-m200 Dosing on Day 4 by 
System Organ Class and Preferred Term 
Qualification 
Safety  
 
Table 14.3.1.2.2 
Summary of Treatment Emergent Adverse Events 
Occurring After IXT-m200 Dosing on Day 4 through 
End of Study by System Organ Class and Preferred 
Term 
Safety 
 


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Table 14.3.1.2.3 
Summary of Treatment Emergent Adverse Events 
Occurring During Inpatient Stay After IXT-m200 
Dosing on Day 4 by System Organ Class and 
Preferred Term 
Safety 
 
Table 14.3.1.2.4 
Summary of Treatment Emergent Adverse Events 
Occurring During Outpatient Follow-up by System 
Organ Class and Preferred Term 
Safety 
 
Table 14.3.1.3.1 
Summary of Treatment Emergent Adverse Events 
Occurring Prior to IXT-m200 Dosing on Day 4 by 
Relationship to METH Challenge Doses 
Qualification 
Safety 
 
Table 14.3.1.3.2 
Summary of Treatment Emergent Adverse Events 
Occurring During Inpatient Stay After IXT-m200 
Dosing on Day 4 by Relationship to METH Challenge 
Doses 
Safety 
 
Table 14.3.1.3.3 
Summary of Treatment Emergent Adverse Events 
Occurring During Outpatient Follow-up by 
Relationship to METH Challenge Doses 
Safety 
 
Table 14.3.1.4.1 
Summary of Treatment Emergent Adverse Events 
Occurring During Inpatient Stay After IXT-m200 
Dosing on Day 4 by Relationship to IXT-m200 
Safety 
 
Table 14.3.1.4.2 
Summary of Treatment Emergent Adverse Events 
Occurring During Outpatient Follow-up by 
Relationship to IXT-m200 
Safety 
 
Table 14.3.1.5.1 
Summary of Treatment Emergent Adverse Events 
Occurring Prior to IXT-m200 Dosing on Day 4 by 
Severity 
Qualification 
Safety 
 
Table 14.3.1.5.2 
Summary of Treatment Emergent Adverse Events 
Occurring During Inpatient Stay After IXT-m200 
Dosing on Day 4 by Severity 
Safety 
 
Table 14.3.1.5.3 
Summary of Treatment Emergent Adverse Events 
Occurring During Outpatient Follow-up by Severity 
Safety 
 
Table 14.3.2 
Listing of Deaths and Other Serious Adverse Events  
All Subjects 
 
Table 14.3.3 
Not part of TFL – Reserved for Narratives in CSR 
 
 
Table 14.3.4 
Listing of Abnormal Laboratory Values 
 
 
Table 14.3.5.1 
Summary of Laboratory Results by Visit 
Safety 
 
Table 14.3.5.2 
Summary of Laboratory Results – Cytokines 
Safety 
 
Table 14.3.6.1 
Summary of Vital Signs by Challenge Day 
Safety 
 
Table 14.3.6.2 
Summary of Vital Signs relative to IXT-m200 Dosing 
Safety 
 
Table 14.3.7.1 
Summary of 12-Lead Electrocardiogram Results by 
Challenge Day 
Safety 
 
Table 14.3.7.2 
Summary of 12-Lead Electrocardiogram Results 
Relative to IXT-m200 Dosing 
Safety 
 


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Page 37 of 39 
Table 14.3.8 
Summary of Immunogenicity Results 
Safety 
Only at 
Final Lock 
 
List of End of Text Listings: 
Output 
Title  
Final 
Analysis 
Only 
Section 16.2.1 – Disposition 
 
Listing 16.2.1.1 
Subject Disposition 
 
Listing 16.2.1.2 
Eligibility Criteria 
 
Listing 16.2.2 
Not part of TFL – Reserved for protocol deviations in CSR 
 
Section 16.2.3 – Excluded Subjects 
 
Listing 16.2.3 
Analysis Sets 
 
Section 16.2.4 – Demographics and Baseline Characteristics 
 
Listing 16.2.4.1 
Subject Demographics 
 
Listing 16.2.4.2 
Medical History 
 
Listing 16.2.4.3 
Prior and Concomitant Medications 
 
Listing 16.2.4.4.1 
DSM-V Criteria Assessments 
 
Listing 16.2.4.4.2 
Recreational Drug Use History 
 
Listing 16.2.4.4.3 
Record of Instances of Non-Therapeutic METH Use 
 
Section 16.2.5 - Compliance 
 
Listing 16.2.5.1 
Study Drug Administration 
 
Listing 16.2.5.2 
IXT-m200 Dosing Information 
 
Section 16.2.6 – Response Data 
 
Listing 16.2.6.1.1 
METH and AMP Plasma Concentrations 
 
Listing 16.2.6.1.2 
METH and AMP Plasma Pharmacokinetic Parameters 
 
Listing 16.2.6.1.3 
METH and AMP Urine Concentrations and Volume 
 
Listing 16.2.6.1.4 
METH and AMP Urine Pharmacokinetic Parameters 
 
Listing 16.2.6.1.5 
IXT-m200 Serum Concentrations 
Only at 
Final Lock 
Listing 16.2.6.1.6 
IXT-m200 Pharmacokinetic Parameters 
Only at 
Final Lock 
Listing 16.2.6.2.1 
Subjective Effects Questionnaire Responses 
 
Listing 16.2.6.2.2 
Subjective Effects Parameters and Change from Baseline 
 
Section 16.2.7 – Adverse Events Data 
 
Listing 16.2.7.1 
Adverse Events 
 


Statistical Analysis Plan 
IVN669GF-166699 
Protocol: M200C-1801 
Version Date: 07-APR-2020  
EDSREP 009 T 01 G 
Page 38 of 39 
Listing 16.2.7.2 
Adverse Events Leading to Study Drug Discontinuation 
 
Section 16.2.8 – Laboratory Data 
 
Listing 16.2.8.1 
Clinical Laboratory Results – Chemistry 
 
Listing 16.2.8.2 
Clinical Laboratory Results – Hematology 
 
Listing 16.2.8.3 
Clinical Laboratory Results – Urinalysis 
 
Listing 16.2.8.4 
Clinical Laboratory Results - Cytokines 
 
Listing 16.2.8.5 
Clinical Laboratory Results – Additional Assessments 
 
Listing 16.2.8.6 
Drug and Alcohol Screen Results 
 
Section 16.2.9-10 – Other Safety Data 
 
Listing 16.2.9 
Vital Signs 
 
Listing 16.2.10 
12-Lead Electrocardiogram Results 
 
Listing 16.2.11 
Immunogenicity Testing 
Only at 
Final Lock 
Listing 16.2.12 
Physical Examination Findings 
 
Listing 16.2.13 
Columbia-Suicide Severity Rating Scale (C-SSRS) Responses 
 
Listing 16.2.14 
Meal Administration 
 
 
Other Appendix Outputs: 
Output 
Title  
Appendix 16.1.7 
Randomization 
Appendix 16.1.9.2.1 
Statistical Appendix – SAS Output for Statistical Analysis of 
Change in METH Pharmacokinetic Parameters following IXT-m200 
Dosing 
Appendix 16.1.9.2.2 
Statistical Appendix – SAS Output for Statistical Analysis of 
Change from Baseline Subjective Effects Parameters by Challenge 
Day 
 


Statistical Analysis Plan 
IVN669GF-166699 
Protocol: M200C-1801 
Version Date: 07-APR-2020  
EDSREP 009 T 01 G 
Page 39 of 39 
Appendix 4: Shells for Post-Text Tables, Figures and Listings 
Shells are provided in a separate document. 
20.0 Document History 
Version Date 
Modified/Reviewed 
By 
Brief Summary of Changes (if created from a 
template, include template code) 
13-MAR-2019 
Reilly Reis 
Kimberly Martens 
Ryan Turncliff 
Emily Mick 
Lynne Pauley 
Created from template, EDSREP 009 T 01 G. 
07-APR-2020 
Reilly Reis 
Emily Mick 
Updated to include description of two separate locks and 
deliveries of TFLs. 
Updated PK parameter diagnostic criteria and 
immunogenicity data outputs. 
Updates based on protocol amendments and CRF 
updates. 

Prot_001.pdf: 
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 


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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 
 
 
 
 






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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. 


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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 
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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 
and the subject treated as needed to reduce or stop the reaction. The infusion will not be restarted. 


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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 
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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 
copy of the ICF will be given to the participants for their records. The rights and welfare of the 


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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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