Clinical trial NCT05096117
Conditions: Alcohol Use Disorder Alcohol Drinking Alcohol Use Disorder (AUD)
Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Start date: 2021-12-13; Completion date: 2023-03-22
Enrollment: 60 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the effects of ASP8062, 25 mg once a day and matched placebo, on alcohol cue-elicited alcohol craving during a human laboratory paradigm after 2 weeks of daily dosing among subjects with moderate to severe alcohol use disorder (AUD) as confirmed by the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5™). Secondary objectives include evaluation of ASP8062, 25 mg once a day, and matched placebo on reduction of alcohol consumption, alcohol craving, cigarette smoking (among smokers), mood, sleep, alcohol use negative consequences, study retention, and safety and tolerability throughout the last 4 weeks of the treatment phase of the study.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: ASP8062 intervention 2: Placebo
Intervention descriptions: intervention 1: ASP8062 is a novel compound with positive allosteric modulator (PAM) activity on the γ-aminobutyric acid type B (GABAB) receptor, 25 mg, 1 x per day for 6 weeks intervention 2: 1 x per day for 6 weeks

Protocol documents:
ICF_002.pdf: 
National Institute on Alcohol Abuse and Alcoholism / Protocol Number HLAB-00, NCT05096117 
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«PiFullName» 
Advarra IRB Approved Version 24 Mar 2022 
Revised «PIApprovalDate» 
 
INFORMED CONSENT FORM 
AND 
AUTHORIZATION TO USE AND DISCLOSE PROTECTED HEALTH INFORMATION 
 
Sponsor / Study Title: 
  
National Institute on Alcohol Abuse and Alcoholism / “Human 
Laboratory Study of ASP8062 for Alcohol Use Disorder” 
 
Protocol Number: 
 
HLAB-003 
 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
KEY INFORMATION  
You are invited to take part in a research study and your participation is voluntary. This 
research study is studying a drug named ASP8062 as a possible treatment for Alcohol Use 
Disorder. One tablet of ASP8062 taken every day for 6 weeks will be compared to taking a 
placebo tablet (like a sugar pill, with no active study drug) every day for 6 weeks. The National 
Institute on Alcohol Abuse and Alcoholism (NIAAA) is sponsoring this research study. 
 
• You are being invited to participate in this study because you have an interest in 
reducing your alcohol consumption. 
• The purpose of this study is to determine if the study drug, ASP8062, decreases craving 
for alcohol and helps people with Alcohol Use Disorder to reduce drinking.  
• The study drug has never been tested for this purpose before and is considered 
“investigational”. This means that it has not been approved by the United States Food 
and Drug Administration (FDA). 
• About 60 people aged 21 and over with moderate to severe alcohol use disorder will 
participate in this study.  
• A total of about 76 mL (about 15 teaspoons or 5 tablespoons) of blood will be collected 
for tests during the study. 
• This research study should take up to 11 weeks of your time. You will be asked to visit 
the clinic about 7 times (possibly a few more) and there is a follow-up phone call at the 
end of the study. 
• You will be given an alcohol breathalyzer test at each clinic visit to ensure you are able 
to provide consent and participate in the study assessments.  
 
 


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• You will be asked to give blood for testing how your liver, kidney and body are 
functioning.  
• You will be asked about your cravings for alcohol and about your alcohol drinking. 
• You will watch some computerized presentations about the benefits of controlling your 
drinking. 
• This study uses a smartphone to check to make sure you took your study drug.  
• You will be asked lots of questions about you and how you are feeling.  
• You may become tired of answering questions. 
• The main benefit to you (or others) for taking part in this study is your drinking habits 
may change. 
• There are several alternative treatments that may be effective for treating alcohol use 
disorder, including other medications and/or counseling. These other treatments are 
not offered to you as part of this research study, but if you decide not to participate, or 
are not eligible, study personnel will give you contact information for existing treatment 
programs in your area. 
 
Please read this form carefully. Take your time to ask the study doctor or study staff as many 
questions about the study as you would like. The study doctor or study staff can explain words 
or information that you do not understand. Reading this form and talking to the study doctor or 
study staff may help you decide whether to take part or not. If you decide to take part in this 
study, you must sign your name at the end of this form and date it.  
 
BACKGROUND AND PURPOSE  
You are being asked to participate in this research study because you would like to change how 
much alcohol you drink. This study will look at how your craving for alcohol changes with the 
study drug and if you cut down or stop drinking alcohol while taking the study drug.   
 
WHAT WILL HAPPEN DURING THE STUDY? 
Screening: 
Before any study-related tests and procedures are performed, you will be asked to read, sign, 
and date this consent document. The screening phase will be completed within 14 days and will 
involve one clinic visit. Additional visits may be requested if laboratory tests need to be 
repeated.  
 
If you decide to volunteer for this study, your first visit will take approximately 2 1/2 to 3 hours 
to complete. This involves a number of tests to make sure that you meet all of the 
requirements for participation and that you can safely take the study drug. You will not be 
given study drug during this first screening visit. 
 
At the beginning of the Screening Visit, your blood alcohol level will be measured using an 
alcohol breathalyzer. If your blood alcohol is greater than 0.000%, you may not be able to 
complete your visit as scheduled. If your blood alcohol level is very slightly higher than 0.000%, 
study staff may give you the option of waiting until it reaches 0.000% to continue with your first 
visit. If your blood alcohol level is 0.080%, that is above the legal limit for driving, or higher and 


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you drove to your visit, study staff will ask you to remain in the clinic until you are capable of 
leaving without risking your (or others) safety. The following screening tests and procedures 
will then be performed to determine if you qualify to take part in this study:  
 
• Provide a valid form of identification (ID). Acceptable forms of ID are as follows: Driver’s 
License, Passport, Military ID, State or National ID, or Medicare or Medicaid card. 
• Provide contact information of friends and/or family in case we cannot contact you. 
• Provide your age, race, ethnicity, and sex at birth. 
• Provide a urine sample to test for drug use and to assess how your kidney is working.  
• Undergo a physical exam to assess your overall health and wellness and have an 
electrocardiogram (ECG) to measure the electrical activity of your heart. 
• Give your medical history and have your weight measured. 
• Have vital signs taken (blood pressure and heart rate).  
• Answer questions about your mental health and desire to quit drinking. 
• Provide a blood sample to assess how your liver, kidneys, and immune system are 
working. 
• If you are a female, provide a urine sample to test for pregnancy.  
• You will be asked about birth control method(s). 
• Provide your daily alcohol use for the past 28 days. 
• Provide the names of any prescription and “over-the-counter” drugs you may be taking 
now or in the recent past. 
• Answer a question about use of cocaine, amphetamines, methamphetamine or MDMA 
– also known as ecstasy or Molly in the past two months 
• Answer questions about any withdrawal symptoms from alcohol. 
• Participate in an exercise (called a cue session) where you will be shown beverages 
(including your favorite alcoholic beverage) and complete computerized questions 
about your craving for the beverages. 
 
This study will use competitive enrollment. This means that when a target number of 
participants begin the study, all further enrollment will be closed. Therefore, it is possible that 
you could be in the screening phase, ready to begin the study, and be discontinued without 
your consent if the target number of participants has already begun the study. 
 
Employees of the study doctor, sponsor, or study drug manufacturer are not allowed to 
participate in this study.  
 
Students of this institution are allowed to participate in this study. If you are a student: 
 
• The decision to participate or not will not affect your grade, recommendations, 
employment or the like. 
• Failure to participate will not have a negative effect on your relationship with the 
study doctor or the faculty. 
 
 


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If you qualify to take part in this study and go on to receive the study treatment, then the 
following will happen:  
 
Study Treatment:  
You will be randomly assigned by chance (like the flip of a coin) to receive either ASP8062 or 
placebo (inactive substance). You will have a 50% (1 in 2) chance of receiving ASP8062 and a 
50% (1 in 2) chance of receiving placebo. This is a double-blind study, which means neither you 
nor the study doctor will know to which of these study drug groups you are assigned. In case of 
an emergency, however, the study doctor can get this information.  
 
You will take your assigned study drug tablet orally (swallowed with water) at bedtime at home. 
 
You will have the following study visits and other procedures:  
 
Study Phase 
Screening 
Study Treatment 
End of 
Study 
Follow-
up Call 
Clinic Visit # 
1 
2 
3 
4 
5 
6 
7 
 
Study Week  
Pre-study 
1 
2 
3 
4 
5 
7 
9 
Urine Drug Test 
X 
X 
X 
X 
X 
X 
X 
 
Medical History 
X 
X 
 
 
 
 
 
 
Physical Exam  
X 
X 
 
 
 
 
 
 
Body Weight 
X 
 
 
 
X 
 
X 
 
Questionnaires 
X 
X 
X 
X 
X 
X 
X 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
 
Blood tests + ECG 
X 
 
 
 
X 
 
X 
 
Pregnancy test (if female) 
X 
X 
 
 
 
 
X 
 
Cue session 
X 
 
 
X 
 
 
 
 
Side effects + medications 
X 
X 
X 
X 
X 
X 
X 
X 
Take control video 
 
X 
X 
X 
X (2 
videos 
at this 
visit) 
X 
X 
 
 
The blood sample will be used to measure study drug levels in your blood and to check how 
your liver, kidneys, and immune system are working. Questionnaires include asking about your 
cravings for alcohol and alcohol withdrawal symptoms, mood, desire to quit drinking, sleep, 
drinking urges, smoking cigarettes, and use of other nicotine products, and about your daily 
alcohol use since your last visit.  You will view an alcohol education program called Take 
Control. You will participate in a cue session (like the one done at the screening visit) where you 
will be shown beverages (including your favorite alcoholic beverage) and complete 
computerized questions about your craving for the beverages. You will be asked how you are 
feeling (side effects of taking the study drug or any new problems) and about any medications 
that you are taking. You will be reminded about using appropriate birth control methods.  


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During this study, you will use a smartphone provided by a company called AiCure, LLC, with its 
primary place of business at 19 West 24th Street, 11th floor, New York, NY 10010, USA 
(“AiCure”). Before starting use of this smartphone, you will be instructed on how to set up the 
smartphone so that it can confirm your identity and register your preferred settings. You will 
also practice several times to learn how to use it. 
 
You may use your personal smartphone by downloading a computer program with assistance 
from the study staff. If you do not have a suitable smartphone, one will be provided by the 
study site. If you are provided with a smartphone, you will not be able to make general phone 
calls, respond to text messages, or use it to access the Internet. You are required to return the 
provided smartphone at the end of the Study.  
 
How you will interact with the smartphone:  
 
• The smartphone will help remind you when it is time to take your study drug. You will 
be required to use the smartphone to monitor each dose of study drug while you are 
enrolled in the study. The smartphone is used to visually confirm that the same person 
uses the smartphone each time, and that the study drug is correct and administered 
properly. It is important that you remember to use the smartphone every time you take 
your study drug.  
• The smartphone will NOT be used to collect and report any emergencies, side effects, or 
adverse events you may experience during the study. If there is something that you 
need to discuss with the site, you should contact them directly or follow procedures for 
reporting a medical emergency.  
 
You will be reimbursed for your additional time when successfully using the smartphone at $1 
United States Dollar (USD) every time you take your study drug. This is a maximum payment of 
$42. The study staff will provide you with a debit card for you to receive the compensation for 
using the smartphone. You will be required to register your payment cards with the company 
providing the payment cards by entering personal information including your name, date of 
birth and home address. Neither AiCure nor Sponsor will have any access to the information 
you provide. 
 
During the registration process in the smartphone, you will be given the option to enter your 
personal telephone number(s), which is voluntary. By submitting your number, you grant the 
study site and AiCure permission to contact you at this number by text messaging or by phone 
if:  
• You are not responding to the prompts or reminders in the application 
• The study staff needs to reach you in regards to the study 
• The study device requires updates or alterations 
 
Information that will be collected by the smartphone:  your study ID, cell phone number if 
provided, phone IMEI (unique phone ID), the video and audio of you using the smartphone, and 
the date and time the video was taken.  


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All of your video recordings and data are encrypted (converted to a code to prevent 
unauthorized access) and will be automatically forwarded to a secure server. The encrypted 
recordings are only accessible by authorized staff of AiCure. The data excluding the video 
recording are securely stored and only accessible to AiCure, healthcare providers and sponsor 
through a website password protected.  
 
The smartphone will be used only for the purpose of making sure you are taking your dose. If 
you are provided with a smartphone, you will not be able to make general phone calls, respond 
to text messages, or use the smartphone to access the Internet. This smartphone uses a very 
sophisticated computer program to confirm that the same person uses the device, and that the 
study drug is correct and taken properly. The smartphone will send a message to a secure 
server, confirming that you took the study drug. The smartphone will record the date and time 
that you took the study drug so that the study site can confirm it was taken for that day.  
 
Before starting use of the smartphone, the study site staff will assist you in set up so that the 
smartphone can confirm your identity and register your preferred settings. Through prompts, 
the smartphone will assist you to practice recording yourself taking the study drug.  
 
The study staff will help you set the smartphone so that it will remind you to take the study 
drug in the evening before bedtime. It is important that you remember to use the smartphone 
every time you take your study drug.  
 
End of Study Visit: 
Because this is a research study, the study drug will be given to you only during this study and 
not after the study is over. Besides the tests described above and in the table above you will be 
given a treatment referral  
 
Follow-up Contact: (2 weeks after last in-clinic visit) 
Two weeks after you complete the study, a study staff member will contact you by telephone to 
ask you questions about your alcohol use and any side effects you may have had since you 
stopped taking the study drug. If study staff is not able to reach you by telephone, they may 
contact friends or family members you provided at screening to get your new contact 
information. Please be aware that if you tell others that you are in this study, this could be a 
risk of your confidentiality. In order to maintain your confidentiality when attempting to 
contact you or a contact person by telephone, the research staff will not say that you are a 
participant in this research study. Once we have contacted you and/or the contacts you gave 
us, your participation in the study will end. 
 
EXPECTATIONS  
If you participate in this study, you will be expected to:  
• Not give the study drug to other people and keep it out of the reach of children 
• Be willing and able to follow the study directions and procedures 
• Tell the study staff about any side effects or problems 
• Ask questions as you think of them 


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• Tell the study doctor or the study staff if you change your mind about staying in the 
study 
• Not participate in any other research studies during this time 
• Participate in all study procedures as instructed 
 
RISKS, SIDE EFFECTS, AND/OR DISCOMFORTS  
In clinical studies of ASP8062 conducted so far, 195 healthy volunteers were given single or 
multiple doses from 0.3 milligrams (mg) to 60 mg. If assigned to the study drug, you will be 
given daily doses of 25 mg per day for 6 weeks in this study. Also, 95 participants with 
fibromyalgia (a medical condition that causes muscle and bone pain, fatigue (tiredness), sleep, 
memory and mood issues), received 30 mg doses over 8 weeks. 
 
You may be required to seek proper medical attention if your blood pressure is above normal 
limits during the study. 
 
Taking part in this research study involves some inconveniences and risks. The main risks are 
discussed below.  
 
For ASP8062: 
Common (greater than or equal to 1/100 to less than 1/10 people) 
• Dizziness and headache 
• Dizziness, vomiting, nausea, loss of coordination, and sleepiness occurs at a higher rate 
when taking the study drug with alcohol 
 
Uncommon (greater than or equal to 1/1,000 to less than 1/100 people) 
• Lightheaded when standing 
• Ear pain 
• Feeling hot 
• Nausea 
• Neck pain 
• Vomiting 
 
Effects during cocaine use 
• Animals exposed to cocaine and ASP8062 at the same time had increases in blood 
pressure. This may occur in humans. Cocaine use can cause a stroke. If you use ASP8062 
with cocaine you may have a greater risk for a stroke (bleeding in your brain or loss of 
blood to your brain). You are expected to not use cocaine in this study. Other drugs such 
as amphetamines, methamphetamine or MDMA that are considered stimulants like 
cocaine may also increase blood pressure when taken with ASP8062. You are expected 
to not use these drugs either during the study.  
 
 
 


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RISKS OF STUDY PROCEDURES 
• Blood samples: Possible side effects from blood drawing include faintness, inflammation 
of the vein, pain, bruising, or bleeding at the site of puncture. There is also a slight 
possibility of infection. 
• Electrocardiogram (ECG): Skin irritation is rare but could occur during an ECG from the 
electrodes or gel that is used. 
• Questionnaires: Some of the questions about your personal habits, lifestyle, emotional 
state and drug and alcohol use may embarrass you. If any question makes you feel 
uncomfortable you may discuss its importance and the need to answer it with the 
specially trained interviewer. You may refuse to answer a question if it is upsetting to 
you.  
• If you are having suicidal thoughts call the study doctor at the telephone number listed 
on the first page of this form. If you feel in crisis, you can call 911 and/or a Nationwide 
Suicide Hotline that is answered 24 hours a day with a skilled, trained counselor. One 
example is the National Suicide Prevention Lifeline at 1-800-273-TALK (8255). 
• You may become bored with answering questionnaires. 
• As part of this research, you may be required to use one or more of the following: a 
phone or web app/ site, an electronic study diary (eDiary), or a device that tracks 
information about you. While using these, information about you may be collected and 
shared with the researchers or people outside of the study. This data includes your 
study ID, cell phone number if provided, phone IMEI (unique phone ID), the video and 
audio of you using the smartphone, and the date and time the video was taken. A 
complete description of the data collection and sharing for an app, eDiary, or device can 
commonly be found in the Terms of Use, End User License Agreement, or Privacy Policy. 
If you would like to read these documents, request a copy or instructions about how to 
access this information from the study doctor. While the Terms of Use, End User License 
Agreement, or Privacy Policy may include statements limiting your rights if you are 
harmed as a result of your use of the app, eDiary, or device in this study, you do not 
release the investigator, sponsor, institution, or agents for responsibilities from 
mistakes. You also do not waive any of your rights as a research participant. 
 
If you receive placebo (the inactive substance) as part of this study, your symptoms of Alcohol 
Use Disorder may not improve or may get worse.  
 
RISKS FROM ALCOHOL WITHDRAWAL 
Some people may experience symptoms of alcohol withdrawal if they stop drinking suddenly. 
At your screening visit, you will be given information to help you recognize the symptoms of 
withdrawal. You will be monitored carefully throughout the study in case you begin to have 
symptoms of alcohol withdrawal. If you experience any of these symptoms, you will be 
instructed to call the clinical site using the 24-hour phone number provided to you. If you have 
serious withdrawal, you should go to the nearest emergency room.  
 
 


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UNFORESEEN RISKS  
Since the study drug ASP8062 is investigational, there may be other risks that are unknown. 
Additionally, there may be unknown risks to a pregnancy, embryo, or fetus if you or your 
female partner becomes pregnant. 
 
BIRTH CONTROL RESTRICTIONS  
Taking the study drug may involve risks to a pregnant woman, an embryo, fetus (unborn baby) 
or nursing infant. Therefore, if you are pregnant, planning to become pregnant, planning to 
father a child, or are breastfeeding a child, you cannot participate in this study. 
 
Females: 
In order to reduce the risk of pregnancy, you should use an effective method of birth control 
while you are participating in this study and for 30 days after your last dose of the study drug. 
Acceptable methods of birth control for use in this study are 
• Oral contraceptives, 
• Contraceptive sponge, 
• Patch, 
• Double barrier (diaphragm/spermicidal or condom/spermicidal), 
• Intrauterine contraceptive system (such as an IUD), 
• Etonogestrel implant, 
• Medroxyprogesterone acetate contraceptive injection,  
• True abstinence: when this is in line with your preferred and usual lifestyle,  
• And/or hormonal vaginal contraceptive ring.  
 
You must not donate ova for at least 30 days following the last dose of ASP8062. 
 
The study doctor or study staff will discuss this with you.  
 
If you become pregnant while you are participating in this study, or within 30 days (one month), 
tell your study doctor or study staff immediately. The study drug will be stopped and your 
participation in this study will be ended.  You will be asked to provide information about the 
health of your new born child. 
 
Males:  
In order to reduce the risk of pregnancy, you should use an effective method of birth control 
while you are participating in this study and for 90 days (three months) after your last dose of 
the study drug. Acceptable methods of birth control for use in this study are  
• Surgical sterilization (vasectomy); 
• Your female partner uses oral contraceptives (combination estrogen/progesterone 
pills), injectable progesterone or sub dermal implants (started at least 14 days prior to 
study drug administration to the male participant)  
• Your female partner uses a medically prescribed topically applied transdermal 
contraceptive patch (started at least 14 days prior to study drug administration to the 
male participant); 


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• Your female partner has undergone tubal ligation (female sterilization) or is 
postmenopausal (one year); 
• Your female partner has undergone placement of an intrauterine device or intrauterine 
system; and, 
• True abstinence: when this is in line with your preferred and usual lifestyle   
 
The study doctor or study staff will discuss this with you.  
 
If your female partner becomes pregnant while you are participating in this study or within 90 
days (three months) after you have stopped taking the study drug, tell your study doctor or 
study staff immediately.  
 
You must not donate sperm for 90 days after the last dose of ASP8062. 
 
ALTERNATIVES TO PARTICIPATION  
You do not have to be in this study to receive treatment for your Alcohol Use Disorder. There 
are other options including: 
• Seeking care for your alcohol use disorder from a licensed therapist, psychiatrist, or 
medical doctor 
• Participation in another study  
• Referral to other available treatment programs in your area 
Please talk to the study doctor about your options before you decide whether or not you will 
take part in this study. 
 
NEW FINDINGS  
Any new important information that is discovered during the study and which may influence 
your willingness to continue participation in the study will be provided to you. 
 
BENEFITS 
You may benefit by viewing Take Control alcohol education modules and learning how much 
you drink and the risks associated with drinking this amount. Participation in this study may or 
may not help you cut back or quit drinking. However, by participating in this study you will 
receive information and advice about reducing your drinking, as well as close medical attention 
and monitoring of your overall well-being. There is, however, no guarantee that you will benefit 
from your participation in this study. Information learned from the study may help other people 
in the future.  
 
 
 


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COMPENSATION FOR PARTICIPATION  
«Compensation» 
 
You will be paid up to a total of up to $595.00 if you complete this study. You will be paid for 
the visits you complete according to the following schedule: 
• $30 for the Screening Visit 
• $50 for the Randomization Visit 
• $65 for the Week 2 Visit 
• $100 for the Week 3 Cue Reactivity Session 
• $75 for Week 4 
• $80 for Week 5  
• $85 for Week 7, the Final Clinic Visit, and  
• $110 for the Final Telephone Follow-Up  
 
If you do not complete the study, for any reason, you will be paid for each study visit you do 
complete.  
 
You will be paid ___________ [“after each visit,” “annually,” “bi-weekly,” etc.] 
 
If you have any questions regarding your compensation for participation, please contact the 
study staff.  
 
CONFIDENTIALITY   
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. 
 
Records of your participation in this study will be held confidential except when sharing the 
information is required by law or as described in this informed consent. Some people and 
organizations may inspect and copy confidential study-related records and review your 
identifiable information. They may need to see these records in order to monitor the research, 
verify the accuracy of the study data, or to analyze data or samples. These groups include: 
• Research study staff at your study site, 
• A limited number of representatives from Astellas Pharma Global Development, the 
drug company providing the study drug, 
• The National Institute on Alcohol Abuse and Alcoholism, who is sponsoring this 
research,  
• The research ethics review board – Advarra IRB (an independent ethics committee that 
reviewed the ethical aspects of this study to help protect the rights and welfare of study 
participants),  
• Fast Track Drugs & Biologics, the group that is monitoring the study data, 
• Government regulatory authorities including the FDA. 
 


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This means that absolute confidentiality cannot be guaranteed. Your study records including 
confidential information about you collected during the study will be kept at a secure location. 
 
While every effort will be made to protect the privacy of your information, absolute 
confidentiality cannot be guaranteed. This does not limit the duty of the researchers and others 
to protect your privacy. 
 
By signing and dating this information and consent form, you consent to the collection, access, 
use and disclosure of your information as described above. 
 
COMPENSATION FOR INJURY  
If you become ill or are injured while you are in the study, get the medical care that you need 
right away. You should inform the healthcare professional treating you that you are 
participating in this study. If you tell the study staff that you think you have been injured then 
they will help you get the care you need.  
 
No medical care, evaluations or financial compensation for research-related injuries or illness 
will be provided. The costs of such additional treatment will be paid by you or by your health 
insurance carrier. You also have the right to pursue legal remedy if you believe that your 
injuries justify such action. Compensation for injury/illness may be payable under the Federal 
Tort Claims Act. The availability of this compensation may vary depending upon the 
circumstances involved and there are certain limitations. 
 
Please be aware that some insurance plans may not pay for research-related injuries. You 
should contact your insurance company for more information 
 
By signing and dating this document, you will not lose any of your legal rights or release anyone 
involved in the research from responsibility for mistakes. 
 
COSTS  
There will be no charge to you for your participation in this study. The study drug, study-related 
procedures, and study visits will be provided at no charge to you or your insurance company. 
You may be responsible for care related to injury or complications that could arise from 
participation in the study. 
 
DATA SHARING AND RESEARCH RESULTS 
Your study data will be shared with the study sponsor, NIAAA, and the company that is 
developing the study drug, Astellas Pharma Global Development. Direct identifiers (such as 
your name, address, or date of birth) will be removed from your private information when 
sharing the study data with NIAAA and Astellas.  
 
 
 


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Advarra IRB Approved Version 24 Mar 2022 
Revised «PIApprovalDate» 
 
If you agree, NIAAA may share your data without direct identifiers as part of the combined 
study database through controlled access without additional informed consent. This means the 
data are made available for other research only after the researcher has obtained approval 
from NIAAA to use the requested data for a particular project. The data will not include direct 
identifiers like your name, medical record number or date of birth. To use your data, 
researchers must promise not to try to re-identify you. You can tell us at the end of this form 
whether you will allow is to share your data in this way.  
 
Researchers are required to publish the results of this study. These results will be based on 
outcomes for the entire group of participants and will not identify you as a participant. No 
individual information about you or your participation in this research will be made public 
without your express written permission. You will not be told directly the results of this 
research; however, after the end of the study, you may request and be provided with the name 
of the study drug that you received, ASP8062 or placebo.  A research article may be published 
that may be available to the public at the end of the study. Research results that are clinically 
relevant, including individual research results, will not be disclosed to you. 
 
There is no set time for destroying the information that will be collected for this study. Your 
permission to use and share the information and data from this study will not expire. 
 
CERTIFICATE OF CONFIDENTIALITY 
This study is covered by a Certificate of Confidentiality (CoC) from the National Institutes of 
Health. All studies funded by the National Institutes of Health that involve identifiable 
information or biological samples are covered by a CoC.  
 
The CoC is issued to protect the study doctors on this study from being forced to tell people 
that are not connected with this study about your participation in this study, even under a 
subpoena. This protection, however, is not absolute. The protection offered by the CoC does 
not stop us from voluntarily reporting information about suspected or known sexual, physical, 
or other abuse of a child or older person, or a participant's threats of violence to self or others. 
 
If any member of the research team is given such information, he or she will make a report to 
the appropriate authorities If you participate in this study, you are protected permanently 
during any time the Certificate is in effect - even if you gave the researcher data before the 
Certificate is issued. Also, because this research is sponsored by NIAAA, staff from NIAAA and 
other DHHS agencies may review records that identify you but only for the purposes of audit for 
quality and accuracy or program evaluation.  
 
Even when a CoC is in place, you must still continue to actively protect your own privacy. If you 
voluntarily give your written consent to anyone to receive information about your participation 
in the research or freely volunteer information to anyone other than the study staff that you 
are a research participant in this study, then we may not use the CoC to withhold this 
information. 
 


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WHOM TO CONTACT ABOUT THIS STUDY 
During the study, if you experience any medical problems, suffer a research-related injury, or 
have questions, concerns or complaints about the study, please contact the study doctor at the 
telephone number listed on the first page of this consent document. If you seek emergency 
care, or hospitalization is required, alert the treating physician that you are participating in this 
research study.  
 
An institutional review board (IRB) is an independent committee established to help protect the 
rights of research participant. If you have any questions about your rights as a research 
participant, and/or concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Participant Adviser 
Advarra IRB 
6100 Merriweather Dr., Suite 600 
Columbia, MD 21044 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Participant Adviser: 
Pro00057799. 
 
VOLUNTARY PARTICIPATION / WITHDRAWAL  
Your decision to participate in this study is voluntary. You may choose to not participate or you 
may withdraw from the study for any reason without penalty or loss of benefits to which you 
are otherwise entitled and without any effect on your future medical care. However, please 
note that the FDA requires that any information collected up to the point of your withdrawal 
cannot be removed from the study. 
 
To withdraw from the study, please contact the study doctor (in writing is preferred). 
 
The study doctor, the sponsor, Advarra IRB, or the FDA can stop your participation at any time 
without your consent for the following reasons: 
• If it appears to be medically harmful to you; 
• If you fail to follow directions for participating in the study; 
• If it is discovered that you do not meet the study requirements; 
• If you or your partner become pregnant 
• You start to drink more alcohol at a level deemed harmful by study staff 
• You are confined in a controlled environment 
• You have a psychiatric crisis 
• You have a physical illness that prevents you from taking the study drug 
• If the study is canceled; or  
• For administrative reasons. 


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If you leave the study for any reason, the study doctor may ask you to have some end-of-study 
tests for your safety.  
 
ADDITIONAL REQUIRED PRIVACY LANGUAGE 
 
By submitting my personal telephone number(s), I grant the Study site and AiCure permission 
to contact me at this number by SMS (text) messaging or by phone if: 
 
• Study drug is not taken or not taken correctly; or 
• The Study smartphone or app requires updates or alterations. 
 
Additionally, I grant the Study site and AiCure permission to contact me on the smartphone-like 
device if my personal telephone number(s) cannot be reached. 
 


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AGREEMENT TO BE IN THE STUDY 
 
This consent form contains important information to help you decide if you want to be in the 
study. If you have any questions that are not answered in this consent form, ask one of the 
study staff.  
 
Please answer YES or NO to the following questions: 
 
A. Is this document in a language you understand? 
 
 
 
 
 
 
 
B. Do you understand the information in this consent form? 
 
 
 
 
 
 
C. Have you been given enough time to ask questions and talk about the study?  
 
 
 
D. Have all of your questions been answered to your satisfaction? 
 
 
 
 
 
E. Do you think you received enough information about the study? 
 
 
 
 
 
F. Do you volunteer to be in this study of your own free will and without being  
pressured by the study doctor or study staff? 
 
 
 
 
 
 
 
 
G. Do you know that you can leave the study at any time without giving 
a reason and without affecting your health care? 
 
 
 
 
 
 
 
H. Do you know that your health records from this study may be reviewed 
by the study sponsor and by government authorities?  
 
 
 
 
 
 
I. Do you know that you cannot be in another study while you are in this study? 
 
 
 
IF YOU ANSWERED “NO” TO ANY OF THE ABOVE QUESTIONS, 
OR YOU ARE UNABLE TO ANSWER ANY OF THE ABOVE QUESTIONS, 
YOU SHOULD NOT SIGN AND DATE THIS CONSENT FORM. 
 
 
 
 


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CONSENT  
I have read and understand the information in this informed consent document. I have had an 
opportunity to ask questions and all of my questions have been answered to my satisfaction. I 
voluntarily agree to participate in this study until I decide otherwise. I do not give up any of my 
legal rights by signing and dating this consent document. I will receive a copy of this signed and 
dated consent document. 
 
 
________________________________________ 
 
 
Participant’s Printed Name  
 
 
________________________________________ 
 
___________   
__________ 
Participant’s Signature 
 
 
 
 
Date 
 
 
Time 
 
________________________________________ 
 
 
Printed Name of the Person Conducting the  
 
 
Consent Discussion   
 
________________________________________ 
 
___________   
__________ 
Signature of the Person Conducting the  
 
 
Date 
 
 
Time  
Consent Discussion   
 
 
 
 
 
 
 
I agree to allow NIAAA to share my data as part of the combined study database through 
controlled access (circle yes or no): Yes / No. 
 
__________________________________ 
Initials / Date 
 
You will receive a signed and dated copy of this consent form to keep.  
 


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CONSENT FORM QUESTIONS 
 
ASP8062 for Alcohol Use Disorder 
 
Check the appropriate response: 
TRUE 
FALSE 
1) If a study participant becomes pregnant while participating in this 
study, she will be taken off the study drug. 
 
 
2) ASP8062 has already been approved by the Food and Drug 
Administration (FDA) as a treatment for alcohol use disorder. 
 
 
3) You will take two pills per day of ASP8062 or placebo. 
 
 
4) You are expected to give truthful answers about your drinking. 
 
 
5) You will be told whether you are receiving ASP8062 or placebo. 
 
 
6) You will have to give blood and urine samples during the course of 
the study. 
 
 
7) The study staff may end your participation in this study if they feel 
that it is in your best interest. 
 
 
8) You will be compensated for your time and travel. 
 
 
9) You must bring your study drug blister packs to every visit. 
 
 
10) You will never be contacted by telephone during the study. 
 
 
11) You must inform the study staff of starting any new medications 
that you take during the study. 
 
 
12) The research data I provide in this study may be made available to 
the general research community, but will be de-identified so that 
any personally identifiable data will removed. 
 
 
 
The correct answers to the questions above have been discussed with me. 
 
 
 
Participant Signature 
 
 


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AUTHORIZATION TO USE AND DISCLOSE PROTECTED HEALTH INFORMATION 
 
If you decide to be in this study, the study doctor and study staff will use and 
share health data about you to conduct the study. Health data may include: 
• Your name 
• Address 
• Phone number 
• Age 
• Medical history 
• Information from your study visits, including all test results 
 
Health data may come from your study records or from existing records kept by 
your doctor or other health care workers.  
 
For this study, the study staff may share health data about you with authorized 
users. Authorized users may include: 
• Representatives of NIAAA 
• Representatives of Fast-Track Drugs and Biologics, LLC, the company hired 
by NIAAA to monitor the study 
• Representatives of Advarra IRB (an Institutional Review Board that reviews 
this study). 
• Representatives of Astellas Pharma Global Development (the company that 
makes the study drug) 
• Representatives AiCure (the company that provides the smart phone 
application) 
• The Food and Drug Administration (FDA) and other US federal and state 
agencies 
• Government agencies to whom certain diseases (like HIV, hepatitis, and 
STDs) must be reported 
• Outside individuals and companies, such as laboratories and data storage 
companies, that work with the researchers and sponsor and need to access 
your information to conduct this study 
 
Your health data will be used to conduct and oversee the research, including for 
instance: 
• To see if the study drug works and is safe 
• To compare the study drug to other drugs 
• For other research activities related to the study drug 


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«PiFullName» 
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Once your health data has been shared with authorized users, it may no longer be 
protected by federal privacy law and could possibly be used or disclosed in ways 
other than those listed here.  
 
Your permission to use and share health data about you will end in 50 years 
unless you revoke it (take it back) sooner.  
 
You may revoke (take back) your permission to use and share health data about 
you at any time by writing to the study doctor at the address listed on the first 
page of this form. If you do this, you will not be able to stay in this study. No new 
health data that identifies you will be gathered after your written request is 
received. However, health data about you that has already been gathered may 
still be used and given to others as described in this form.  
 
Your right to access your health data in the study records will be suspended 
during the study to keep from changing the study results. When the study is over, 
you can access your study health data. 
 
If you decide not to sign and date this form, you will not be able to take part in 
the study. 
 
STATEMENT OF AUTHORIZATION 
I have read this form and its contents were explained. My questions have been 
answered. I voluntarily agree to allow 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 and 
dating this form.  
 
__________________________________ 
Printed Name of Participant 
 
 
__________________________________ 
 
 
__________  
Signature of Participant  
 
 
 
 
Date  
 
 

Prot_000.pdf: 
ASP8062 – Human Laboratory Paradigm 
NIAAA, NIH 
Protocol Number: HLAB-003 
1 
NCT05096117
Protocol Number: HLAB-003 
Human Laboratory Study of ASP8062 for Alcohol Use Disorder 
Sponsor: 
National Institute on Alcohol Abuse and Alcoholism 
(NIAAA) National Institutes of Health 
Division of Medications Development 
6700B Rockledge Dr. 
Bethesda, MD 20892-6902 
NIAAA Medications 
Development Team 
(Sponsor’s Representatives) 
Raye Z. Litten, Ph.D. (Lead) 
Fax: 301-443-8774 
E-mail: rlitten@mail.nih.gov
Daniel E. Falk, Ph.D.  
Tel: (301) 443-0788 
Email: falkde@mail.nih.gov 
Jenica Tapocik Patterson, Ph.D. 
Tel (301) 827-6166 
Jenica.patterson@nih.gov  
Joanne Fertig, Ph.D.  
Tel: (301) 443-0635 
Email: jfertig@mail.nih.gov 
Megan Ryan, M.B.A, CCRP 
NIAAA (address above) 
Tel: (301) 443-4225 
Email: mryan1@mail.nih.gov 
Study Coordinating Center: 
Fast-Track Drugs & Biologics, LLC 
20010 Fisher Avenue, Suite G 
Poolesville, MD, 20837 
Janet H. Ransom, Ph.D.  
Project Director 
Tel: (301) 349-2059 
Email: jransom@fasttrackresearch.com 
Charles Scott, Ph.D. 
Director, Biostatistics 
Medical Monitor: 
Bryan Smith, M.D. 
Fast-Track Drugs & Biologics, LLC 
Tel: (301) 807-8548 
Email: bsmith@fasttrackresearch.com 
Version 7: Date: 12Aug2022 
NIAAA Confidential 


ASP8062 – Human Laboratory Paradigm 
 
 
 
 
 
 
 
 
 
 
 
 
NIAAA, NIH 
Protocol Number: HLAB-003 
 
Version 7: Date: 12Aug2022 
2  
 
NIAAA Confidential 
Backup Medical Monitor: 
 
Lorenzo Leggio, M.D., Ph.D., M.Sc. 
Chief, Section on Clinical Psychoneuroendocrinology and 
Neuropsychopharmacology  
Biomedical Research Center 
251 Bayview Boulevard 
Suite 200, Room 04A511 
Baltimore, MD 21224 
Mobile: 240-478-1503 
Email: lorenzo.leggio@nih.gov  
 
 
This document is a confidential communication of NIAAA. Acceptance of this document 
constitutes agreement by the recipient that no unpublished information contained herein 
will be published or disclosed without NIAAA’s prior written approval, except that this 
document may be disclosed to appropriate Institutional Review Boards under the 
condition that they are requested to keep it confidential. In addition, some information 
provided in this document is the property of AiCure (“Platform Provider”), and should 
not be disclosed to others without written authorization from the Platform Provider, 
except to the extent necessary to ensure adequate conduct of the Study. 
 
 
 
 
 
 
 
 
 
 
 
STATEMENT OF COMPLIANCE 
 
The study will be carried out in accordance with Good Clinical Practice (GCP) as required by the 
following: 
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies 
(45 CRF Part 46, 21 CFR Part 50, 21 CFR Part 56 and 21 CFR Part 312) 
• International Conference on Harmonisation (ICH) E6 
All key personnel (all individuals responsible for the design and conduct of this study) have 
completed Human Subjects Protection Training. 
 


ASP8062 – Human Laboratory Paradigm 
 
 
 
 
 
 
 
 
 
 
 
 
NIAAA, NIH 
Protocol Number: HLAB-003 
 
Version 7: Date: 12Aug2022 
3  
 
NIAAA Confidential 
1. 
Protocol Synopsis 
Name of Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA) 
Name of Investigational Product: ASP8062  
Name of Active Ingredient: ASP8062  
Protocol Number: HLAB-003 
Study Title: Human Laboratory Study of ASP8062 for Alcohol Use Disorder 
Sponsor’s Representative: Raye Litten, Ph.D. 
Clinical Centers/PIs: Three clinical sites will participate in this study. 
Study Period: Approximately 1 year 
Phase of Development: 2a 
Objectives: 
Primary: The primary objective of this study is to evaluate the effects of ASP8062, 25 mg once a day and 
matched placebo, on alcohol cue-elicited alcohol craving during a human laboratory paradigm after 2 weeks of 
daily dosing among subjects with moderate to severe alcohol use disorder (AUD) as confirmed by the Diagnostic 
and Statistical Manual of Mental Disorders – Fifth Edition (DSM-5™). 
Secondary: Secondary objectives include evaluation of ASP8062, 25 mg once a day, and matched placebo on 
reduction of alcohol consumption, alcohol craving, cigarette smoking (among smokers) and nicotine use (among 
nicotine users), mood, sleep, alcohol use negative consequences, study retention, and safety and tolerability 
throughout the last 4 weeks of the treatment phase of the study. 
Methodology: This study is a 2-arm, double-blind, randomized, placebo-controlled, parallel group, 3-site study 
designed to assess the effects of ASP8062 as compared with placebo on responses to in vivo alcohol cue exposure 
in the human laboratory setting. After signing informed consent, subjects will be screened for eligibility and have 
other baseline assessments. Screening is permitted over a 14-day period and most baseline assessments will be 
performed on the day of randomization. Assessments include alcohol breathalyzer test (before signing consent), 
medical history, physical examination, weight, vital signs, electrocardiogram (ECG), drinking history by the 
timeline follow-back (TLFB) method, Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-
AR), prior medication use, MINI neuropsychiatric interview, urine drug test, smoking quantity frequency and 
nicotine use interview, clinical laboratory tests including chemistry, hematology, medical urinalysis, alcohol 
craving responses during a baseline cue reactivity session, Columbia Suicide Severity Rating Scale (C-SSRS), 
drinking goal, Penn Alcohol Craving Scale (PACS), Pittsburg Sleep Quality Index (PSQI), PROMIS Alcohol 
Negative Consequences short form, Profile of Moods State (POMS), Hyperkatifeia Scale and confirmation that 
subjects are treatment seeking and desire a reduction or cessation of drinking. Women of child-bearing potential 
will have a pregnancy test.  
If eligible for the study, 60 subjects will be randomized using a stratified permuted block randomization 
procedure with “clinical site” as the stratification variable in an approximate 1:1 ratio (targeting 30 subjects per 
group) to receive either ASP8062 25 mg once daily or matched placebo for 6 weeks.  
Subjects will be seen in the clinic at screening, at randomization and 5 other times during the study. A final 
follow-up telephone interview will occur ~2 weeks after the end of study in-clinic visit. Two cue reactivity 
sessions will be conducted. The first will be during screening (named pretreatment session) and the second will 
be after two weeks of investigational product administration at Study Week 3. During these cue sessions, subjects 
will be presented with water, followed by alcohol and will be asked to respond to 4 individual visual analog 
scales (VAS) items assessing alcohol craving and 1 item assessing beverage liking. Other assessments during the 
treatment period include TLFB, clinical laboratory tests, blood for serum levels of study drug for determining 
medication compliance, vital signs, ECG, concomitant medications, CIWA-AR, C-SSRS, pregnancy test, male 
and female birth control methods, adverse events (AEs), PACS, smoking quantity/frequency, PSQI, and POMS. 
The end of study visit will include the other assessments performed during the treatment phase and an Exit 
Interview, PROMIS questionnaire, and a treatment referral. 


ASP8062 – Human Laboratory Paradigm 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol Number: HLAB-003 
 
Version 7: Date: 12Aug2022 
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Number of Subjects (Planned): 60 
Main Inclusion/Exclusion Criteria: Subjects will be male and female at least 21 years of age with 4 or more 
DSM-5™ symptoms of AUD (moderate to severe AUD). They must also be seeking treatment for AUD and if 
male, report drinking an average of at least 28 drinks per week or if female report drinking an average of at 
least 21 drinks per week prior to consent, and have at least 1 heavy drinking day (4 or more drinks per day for 
women/5 or more drinks per day for men) during the 7-day period prior to randomization.  
Investigational Product, Dosage and Mode of Administration: 
The target doses are 25 mg tablet of ASP8062 by oral administration once daily at bedtime for 6 weeks.  
Reference Therapy, Dosage and Mode of Administration: Subjects in the placebo group will take an 
equivalent number of identically matched placebo tablets (one per day) by oral administration once daily at 
bedtime for 6 weeks. 
Duration of Study: Each subject will participate in the study for up to 11 weeks, including up to 2 weeks of 
screening, 6 weeks of treatment, one end-of-study visit during the week following the last treatment dose, 
and a final telephone contact ~2 weeks after completing treatment for a safety follow-up. 
Criteria for Evaluation: 
Primary: The primary efficacy endpoint is the “strength” of alcohol craving Visual Analog Scale (VAS) score 
(item 1 below) upon presentation of the alcohol during the cue session at Week 3 – after two weeks of 
investigational product treatment. 
Confirmatory secondary endpoints include the VAS scores for the other 3 VAS scales (items 2 through 4 below) 
and the average score of the 4 VAS craving items; and the difference score (alcohol cue VAS score minus water 
cue VAS score) for all 4 of the individual VAS craving items and their average score. The beverage liking VAS 
item is also a confirmatory secondary endpoint. The 4 VAS craving items in order of appearance are: 
1. 
How strong is your craving to drink alcohol? - note this is the primary efficacy endpoint  
2.      Having a drink would make things just perfect.  
3. 
If I could drink alcohol now, I would drink it. 
4. 
It would be hard to turn down a drink right now. 
The beverage liking item is: How much did you like the beverage just shown to you? 
Secondary: Secondary efficacy endpoints will be analyzed over the last 4 weeks of the treatment period. 
1. 
Percentage of subjects with no heavy drinking days. A “heavy drinking day” is 4 or more drinks 
per drinking day for women and 5 or more drinks per drinking day for men. 
2. 
Percentage of subjects abstinent from alcohol. 
3. 
Percentage of subjects with at least a World Health Organization (WHO) 2-level decrease in 
alcohol consumption. 
4. 
Percentage of subjects with at least a WHO 1-level decrease in alcohol consumption. 
5. 
Percentage of days abstinent per week. 
6. 
Percentage of heavy drinking days per week. 
7. 
Percentage of very heavy drinking days per week. A “very heavy drinking day” is 8 or more drinks 
per drinking day for women and 10 or more drinks per drinking day for men. 
8. 
Weekly mean number of drinks per week. 
9. 
Weekly mean drinks per drinking day. 
10. Cigarettes smoked per week among smokers. 
11. Percentage of subjects with no nicotine use among those reporting nicotine use at baseline. 
12. Alcohol craving score (PACS). 
13. Sleep quality (PSQI) score (and subscale scores). 
14. Profile of Mood States (POMS) score (and subscale scores). 
15. PROMIS Alcohol Negative Consequences score. 
Safety Endpoints: Safety endpoints will be analyzed over the entire treatment and follow-up period. 
1. 
Vital signs 


ASP8062 – Human Laboratory Paradigm 
 
 
 
 
 
 
 
 
 
 
 
 
NIAAA, NIH 
Protocol Number: HLAB-003 
 
Version 7: Date: 12Aug2022 
5  
 
NIAAA Confidential 
2. 
Body weight 
3. 
Clinical laboratory parameters 
4. 
BAC by breathalyzer 
5. 
Urine drug tests 
6. 
AEs  
7. 
ECG results 
8. 
CIWA-AR scores 
9. 
Frequency of subjects with suicidal ideation at any time during the treatment period (C-SSRS) 
10. Concomitant medication use 
11. Alcohol Craving Questionnaire – Short Form – Revised (ACQ-SF-SR) score (pre- and post-cue 
response sessions) 
Compliance: Self report of compliance with study drug self-administration is confirmed by digital photography 
(AiCure software) with investigational products and ASP8062 plasma levels.  
Statistical Methods (Data Analysis): 
Analysis Populations: 
Modified intention-to-treat (mITT) Analysis Set: The mITT set is defined as subjects randomized to 
participate in the study that took at least one dose of investigational product and had a non-missing VAS 
craving primary endpoint. 
Evaluable Analysis Set: The evaluable analysis set for the secondary endpoints is defined as those subjects 
randomized to the study who took at least 1 tablet per day for at least 80% of days in Weeks 1-6. 
Safety Analysis Set: The safety analysis set includes all subjects who took at least one dose of 
investigational product.  
Analysis of the Primary Efficacy Endpoint: Each subject will have an alcohol cue VAS score for “strength” 
of alcohol craving score during the treatment alcohol cue session that is the primary endpoint. Analysis of 
covariance (ANCOVA) with the “strength” of alcohol craving value as the dependent variable and the 
pretreatment “strength’ of alcohol craving score as an independent fixed effect. Clinical site will also be 
included as an independent factor. The ASP8062 group will be compared to the Placebo group. No imputation 
for missing endpoint data will be performed.  
Analysis of the Secondary Endpoints: There are 3 additional questions asked during the cue session for each 
beverage cue. Each of these questions will be analyzed in the same manner as the primary endpoint. An overall 
mean of the 4 questions will also be analyzed in the same manner. The difference between the first alcohol cue 
and water cue for each VAS item will be computed at both the pre and post treatment time points. The difference 
values for each VAS item and the average difference will be analyzed similarly to the primary endpoint. 
Continuous secondary endpoints (percent heavy drinking days, percent very heavy drinking days, percent days 
abstinent, drinks per week, drinks per drinking day, number of cigarettes smoked per week, PACS, POMS, and 
PSQI score) during the last 4 weeks of treatment period will be analyzed using a mixed-effects model with site, 
assessment time, and baseline drinking as fixed factors. PROMIS will be analyzed with analysis of covariance 
model with baseline and treatment as factors. Models will also include time by treatment group interaction term. 
Additional covariates may be included that are significantly correlated with outcome and/or if there are 
differences across the treatment groups. 
Analysis of the dichotomous secondary endpoints (percentage subjects with no heavy drinking days, percentage 
subjects abstinent from alcohol, percentage of subjects achieving at least a one and two-level shift in WHO 
alcohol consumption, and percentage of subjects with no nicotine use among subjects with any use during the 
week before randomization) during the last 4 weeks of treatment period will be conducted via logistic 
regression. Covariates may be included provided there are a sufficient number of events.  
No imputation for missing endpoint data will be performed for secondary endpoints.  
Safety Analyses: AEs will be coded using the most recent version of the Medical Dictionary of Regulatory 
Activities (MedDRA) preferred terms and will be grouped by system, organ, and class (SOC) designation. The 
severity, frequency, and relationship of AEs to investigational product will be presented by preferred term by 
SOC grouping. Listings of each individual AE including start date, stop date, severity, relationship, outcome, 
and duration will be provided. Each AE (based on preferred terminology) will be counted once only for a given 


ASP8062 – Human Laboratory Paradigm 
 
 
 
 
 
 
 
 
 
 
 
 
NIAAA, NIH 
Protocol Number: HLAB-003 
 
Version 7: Date: 12Aug2022 
6  
 
NIAAA Confidential 
study subject. If the same AE occurred on multiple occasions, the highest severity and relationship to 
investigational product will be assumed. Thus, study participants are not counted multiple times in a given 
numerator in the calculation of frequencies for a specific AE. Laboratory data, vital signs, ECG results, alcohol 
breathalyzer results, urine drug test results, and CIWA scores will be reported as summary statistics. The 
numbers and proportion of subjects who reported CIWA scores ≥ 10 at any time after the start of dosing will be 
presented. Changes in clinical laboratory tests and vital signs will also be presented as summary statistics of 
change from baseline. The number and percentage of subjects with a higher ACQ-SF-R score post cue session 
will be provided by treatment group. 
Compliance and Participation Outcomes: Medication compliance is defined as the amount of investigational 
products taken as a proportion of the total amount prescribed. Compliance will also be evaluated by 
determining the proportion of subjects who were prescribed ASP8062, reported taking ASP8062 (by AiCure 
assessment), and had a plasma sample with detectable ASP8062. The participation rate is the percentage of 
subjects with complete drinking data. Compliance and participation rates will be reported on a weekly basis and 
across the entire trial duration. Compliance by ASP8062 plasma levels will be reported as number and 
percentage of subjects with a level above the limit of detection at each time point among subjects who were 
prescribed ASP8062. Compliance with tablet ingestion will be confirmed by AiCure assessment or subject’s 
self-report, if AiCure data is not available. Descriptive statistics will also be provided. 
Baseline Descriptive Statistics: Summaries of the characteristics of the subjects in each of the study groups at 
baseline will be prepared for the mITT, evaluable, and safety analysis sets. Baseline characteristics will be 
compared between the ASP8062 group and placebo group using appropriate statistical methods. 
 
 

SAP_001.pdf: 
 
STATISTICAL ANALYSIS PLAN 
 
PROTOCOL NO: HLAB-003 
 
Human Laboratory Study of ASP8062 for Alcohol Use Disorder 
Protocol Version No.: 6.0  Version Date: 13Jun2022 
 
Study Sponsor: 
National Institute on Alcohol Abuse and Alcoholism 
Plan Authors: 
Charles B. Scott, Ph.D.  
Director of Biostatistics 
 
Janet H. Ransom, Ph.D. 
President 
Fast-Track Drugs & Biologics, LLC 
20010 Fisher Avenue, Suite G 
Poolesville, MD, 20837 
 
Daniel E. Falk, Ph.D. 
 Health Science Administrator  
Division of Medications Development 
National Institute on Alcohol Abuse and Alcoholism 
National Institutes of Health 
6700B Rockledge Dr 
Bethesda MD 20892-6902 
 
Version Number 2.0 
Date: 13 June 2022 
NCT05096117 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Table of Contents 
1. 
ABBREVIATIONS ............................................................................................................. 11 
2. 
INTRODUCTION ............................................................................................................... 13 
3. 
PROTOCOL SUMMARY .................................................................................................. 14 
3.1. 
Study Objectives ..................................................................................................... 14 
3.1.1. 
Primary ...................................................................................................... 14 
3.1.2. 
Secondary .................................................................................................. 14 
3.2. 
Study Design .......................................................................................................... 14 
3.3. 
Study Endpoints ..................................................................................................... 20 
3.3.1. 
Primary Efficacy Endpoint ........................................................................ 20 
3.3.2. 
Secondary Efficacy Endpoints .................................................................. 20 
3.3.3. 
Safety Endpoints........................................................................................ 21 
3.3.4. 
Compliance ................................................................................................ 21 
4. 
DEFINITION OF ANALYSIS SETS ................................................................................. 22 
5. 
ASSSESSMENT AND JUSTIFICATION OF STUDY ENDPOINTS .............................. 23 
5.1. 
Alcohol Craving Visual Analog Scales .................................................................. 23 
5.2. 
Alcohol Consumption Endpoints ........................................................................... 23 
5.2.1. 
Daily Quantity of Alcohol Consumption .................................................. 23 
5.2.2. 
Drinking Days ........................................................................................... 23 
5.2.3. 
Very Heavy and Heavy Drinking Day ...................................................... 24 
5.2.4. 
Days at Risk .............................................................................................. 24 
5.2.5. 
Percentage of Subjects with No Heavy Drinking Days and Percentage of 
Subjects Abstinent from Alcohol .............................................................. 24 
5.2.6. 
Weekly Percentage of Heavy Drinking Days and Weekly Percentage of 
Days Abstinent .......................................................................................... 25 
5.2.7. 
Weekly Mean Number of Drinks and Weekly Mean Number of Drinks per 
Drinking Day ............................................................................................. 25 
5.2.8. 
World Health Organization Drinking Risk Categorical Scale ................... 25 
5.3. 
Alcohol-Related Craving, Consequences, and Withdrawal ................................... 25 
5.4. 
Mood ...................................................................................................................... 26 
5.5. 
Sleep Quality .......................................................................................................... 27 
5.6. 
Cigarette Smoking Quantity-Frequency and Nicotine Use Questionnaire ............. 27 
6. 
HYPOTHESES TO BE TESTED ....................................................................................... 29 
6.1. 
Primary Efficacy Endpoint ..................................................................................... 29 
6.2. 
Secondary Efficacy Endpoints ............................................................................... 29 
7. 
SAMPLE SIZE CONSIDERATIONS ................................................................................ 30 
8. 
DATA QUALITY ASSURANCE ...................................................................................... 31 
9. 
STATISTICAL CONSIDERATIONS ................................................................................ 32 
9.1. 
General Considerations .......................................................................................... 32 
9.2. 
Participant Accountability and Protocol Deviations .............................................. 32 
9.3. 
Demographics and Other Baseline Characteristics ................................................ 32 
9.4. 
Efficacy Analysis ................................................................................................... 33 
9.4.1. 
Primary Analysis of the Primary Efficacy Endpoint ................................. 33 
9.4.2. 
Confirmatory Secondary Endpoints .......................................................... 33 
9.4.3. 
Analysis of the Secondary Efficacy Endpoints ......................................... 33 


 
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9.4.3.1. 
Secondary Drinking Endpoints .............................................. 34 
9.4.3.2. 
Alcohol Consequences and Craving Scales ........................... 34 
9.4.3.3. 
Smoking and Any Nicotine Use ............................................ 35 
9.4.3.4. 
Sleep and Mood Scales .......................................................... 35 
9.4.4. 
Covariate Adjustment for the Analysis of Secondary Efficacy Endpoints 35 
9.5. 
Handling of Missing Data ...................................................................................... 36 
9.6. 
Safety Analysis ....................................................................................................... 36 
9.6.1. 
Adverse Events .......................................................................................... 36 
9.6.2. 
Clinical Laboratory and Point of Care Tests ............................................. 36 
9.6.3. 
Vital Signs, ECG, and Body Weight ......................................................... 36 
9.6.4. 
CIWA-AR Scores ...................................................................................... 37 
9.6.5. 
ACQ-SF-R Scores ..................................................................................... 37 
9.7. 
Drug Exposure and Retention Analyses ................................................................. 37 
9.8. 
Blood Alcohol Content ........................................................................................... 37 
9.9. 
Exploratory and Ad Hoc Analyses ......................................................................... 37 
9.9.1. 
Hyperkatifeia Scale ................................................................................... 37 
9.9.2 
Supplemental Exploratory Analysis .......................................................... 37 
10. 
VALIDATION OF PROGRAMMING CODE ................................................................... 38 
11. 
REFERENCES .................................................................................................................... 39 
12. 
TABLE, LISTING, AND FIGURE SHELLS ..................................................................... 41 
12.1. 
Tables ..................................................................................................................... 41 
12.1.1. Subject Disposition, Participation, Compliance ........................................ 41 
12.1.2. Demographic and Baseline Characteristics ............................................... 50 
12.1.3. Primary Efficacy Endpoint ........................................................................ 69 
12.1.4. Confirmatory Secondary Efficacy Endpoints ............................................ 73 
12.1.5. Secondary Efficacy Endpoints .................................................................. 82 
12.1.6. Safety Analyses ......................................................................................... 97 
12.2. 
Listings ................................................................................................................. 113 
12.3. 
Figures .................................................................................................................. 141 
 
List of Tables 
Table 1: 
Subject Disposition - All Randomized Subjects .................................................................. 42 
Table 2: 
Exposure to Investigational Products Using AICure Data – mITT Subjects ...................... 44 
Table 3: 
Total Exposure to Investigational Products Using AICure Data – Evaluable Subjects ...... 44 
Table 4: 
Compliance to Investigational Products Using AICure Data – mITT Subjects .................. 45 
Table 5: 
Compliance to Investigational Products Using AICure Data – Evaluable Subjects ............ 45 
Table 6: 
AiCure  Interventions mITT Subjects ................................................................................. 45 
Table 7: 
 AiCure  Interventions  – Evaluable Subjects ...................................................................... 45 
Table 8: 
Summary of ASP8062 and Metabolite Plasma Levels – ASP8062 Arm Only (mITT 
Subjects) .............................................................................................................................. 46 
Table 9: 
Summary of ASP8062 Plasma Levels – ASP8062 Arm Only (Evaluable Subjects) .......... 47 
Table 10: 
AiCure Report of ASP8062 Versus ASP8062 Plasma Levels – mITT Subjects................. 47 


 
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Table 11:  
AiCure Report of ASP8062 Versus ASP8062 Plasma Levels – Evaluable Subjects .......... 47 
Table 12: 
 Exit Interview – mITT Subjects ......................................................................................... 47 
Table 13: 
 Exit Interview – Evaluable Subjects ................................................................................... 48 
Table 14: 
 Dropouts by Treatment Group and Week – mITT Subjects ............................................... 49 
Table 15: 
Number and Percent of Subjects Using Brief Drinking Questions after Discontinuing 
TLFB – mITT Subjects ....................................................................................................... 49 
Table 16: 
Demographic Characteristics - mITT Subjects ................................................................... 51 
Table 17: 
Demographic Characteristics – Evaluable Subjects ............................................................ 51 
Table 18: 
Screening Cue Reactivity – mITT Subjects ........................................................................ 52 
Table 19: 
Screening Cue Reactivity – Evaluable Subjects .................................................................. 56 
Table 20: 
Psychiatric Baseline Characteristics – mITT Subjects ........................................................ 57 
Table 21:  
Medical History – mITT Subjects ....................................................................................... 57 
Table 22: 
Baseline POMS – mITT Subjects ........................................................................................ 58 
Table 23: 
Baseline POMS – Evaluable Subjects ................................................................................. 59 
Table 24: 
Baseline PSQI – mITT Subjects .......................................................................................... 59 
Table 25: 
 Baseline PSQI – Evaluable Subjects .................................................................................. 60 
Table 26: 
Baseline Drinking-related Behavior and Characteristics – mITT Subjects ......................... 61 
Table 27: 
 Baseline Drinking-related Behavior and Characteristics – Evaluable Subjects ................. 62 
Table 28: 
Baseline Drinking by TLFB – mITT Subjects .................................................................... 62 
Table 29: 
Baseline Drinking by TLFB – Evaluable Subjects .............................................................. 64 
Table 30: 
Baseline Alcohol-Related Craving, Consequences, Withdrawal and Hyperkatifeia – mITT 
Subjects ............................................................................................................................... 65 
Table 31: 
Baseline Alcohol-Related Craving, Consequences, Withdrawal and Hyperkatifeia – 
Evaluable Subjects............................................................................................................... 67 
Table 32: 
Baseline Other Substance Use – mITT Subjects ................................................................. 67 
Table 33: 
Baseline Other Substance Use – Evaluable Subjects .......................................................... 68 
Table 34: 
Week 3 Strength of Craving Scores – mITT Subjects ......................................................... 70 
Table 35: 
Week 3 Strength of Craving Scores – Evaluable Subjects .................................................. 71 
Table 36: 
ANCOVA Strength of Craving – mITT Subjects ............................................................... 71 
Table 37: 
ANCOVA Strength of Craving – Evaluable Subjects ......................................................... 72 
Table 38:  
ANCOVA Strength of Craving (Difference Alcohol-Water) – mITT Subjects .................. 74 
Table 39: 
ANCOVA Strength of Craving (Difference Alcohol-Water)  – Evaluable Subjects .......... 74 
Table 40: 
Drinking Makes Things Perfect Scores – mITT Subjects ................................................... 75 


 
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Table 41: 
Drinking Makes Things Perfect Scores – Evaluable Subjects ............................................. 76 
Table 42: 
ANCOVA Drinking Makes Things Perfect  – mITT Subjects ............................................ 76 
Table 43: 
ANCOVA Drinking Makes Things Perfect  – Evaluable Subjects ..................................... 77 
Table 44: 
ANCOVA Drinking Makes Things Perfect (Difference Alcohol-Water) – mITT Subjects 77 
Table 45: 
ANCOVA Drinking Makes Things Perfect (Difference Alcohol-Water) – Evaluable 
Subjects ............................................................................................................................... 78 
Table 46: 
Drink Now Scores– mITT Subjects .................................................................................... 78 
Table 47: 
Drink Now Scores – Evaluable Subjects ............................................................................. 79 
Table 48: 
ANCOVA Drink Now  – mITT Subjects ............................................................................ 79 
Table 49: 
ANCOVA Drink Now  – Evaluable Subjects ..................................................................... 80 
Table 50: 
ANCOVA Drink Now (Difference Alcohol-Water) – mITT Subjects ................................ 80 
Table 51: 
ANCOVA Drink Now (Difference Alcohol-Water) – Evaluable Subjects ......................... 80 
Table 52: 
Turn Down Drink Scores – mITT Subjects ......................................................................... 80 
Table 53: 
Turn Down Drink Scores – Evaluable Subjects .................................................................. 80 
Table 54: 
ANCOVA Turn Down Drink – mITT Subjects .................................................................. 80 
Table 55: 
ANCOVA Turn Down Drink  – Evaluable Subjects ........................................................... 81 
Table 56: 
ANCOVA Turn Down Drink (Difference Alcohol-Water) – mITT Subjects ..................... 81 
Table 57: 
ANCOVA Turn Down Drink (Difference Alcohol-Water) – Evaluable Subjects .............. 81 
Table 58: 
Average of Cue Scores – mITT Subjects ............................................................................ 81 
Table 59: 
Average of Cue Scores – Evaluable Subjects ...................................................................... 81 
Table 60:  
ANCOVA Average of Cue Scores – mITT Subjects .......................................................... 81 
Table 61: 
ANCOVA Average of Cue Scores – Evaluable Subjects .................................................... 81 
Table 62: 
ANCOVA Average of Cue Scores (Difference Alcohol-Water) – mITT Subjects ............. 81 
Table 63: 
ANCOVA Average of Cue Scores (Difference Alcohol-Water) – Evaluable Subjects ...... 81 
Table 64: 
Beverage Liking Scores – mITT Subjects ........................................................................... 81 
Table 65: 
Beverage Liking Scores – Evaluable Subjects .................................................................... 81 
Table 66: 
Percentage of Subjects No Heavy Drinking Days Weeks 3-6 – mITT Subjects ................. 83 
Table 67: 
Percentage of Subjects with No Heavy Drinking Days Weeks 3-6 – Full Model Logistic 
Regression (mITT) .............................................................................................................. 83 
Table 68: 
Percentage of Subjects Abstinent from Alcohol Weeks 3-6 – mITT Subjects .................... 84 
Table 69: 
Percentage of Subjects Abstinent from Alcohol Weeks 3-6 – Full Model Logistic 
Regression (mITT) .............................................................................................................. 84 
Table 70:  
WHO 1-Level Decrease in Alcohol Consumption (mITT) – Weeks 3-6 ............................ 85 


 
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Table 71: 
WHO 1-Level Decrease in Alcohol Consumption (mITT) – Full Model, Logistic 
Regression, Weeks 2-5 ........................................................................................................ 85 
Table 72: 
WHO 2-Level Decrease in Alcohol Consumption (mITT) – Weeks 3-6 ............................ 86 
Table 73: 
WHO 2-Level Decrease in Alcohol Consumption (mITT) – Full Model, Logistic 
Regression, Weeks 3-6 ........................................................................................................ 86 
Table 74: 
Percentage of Days Abstinent per Week (mITT) – Weeks 3-6 ........................................... 86 
Table 75: 
Percentage of Days Abstinent per Week (mITT) -- Full Model, Mixed Effects, Weeks 3-687 
Table 76: 
Percentage of Heavy Drinking Days per Week (mITT) – Weeks 3-6 ................................. 88 
Table 77: 
Percentage of Heavy Drinking Days per Week (mITT) – Full Model, Mixed Effects, 
Weeks 3-6 ............................................................................................................................ 88 
Table 78: 
Percentage of Very Heavy Drinking Days per Week (mITT) – Weeks 3-6 ........................ 88 
Table 79: 
Percentage of Very Heavy Drinking Days per Week (mITT) – Full Model, Mixed Effects, 
Weeks 3-6 ............................................................................................................................ 88 
Table 80: 
Drinks per Week (mITT) – Weeks 3-6 ................................................................................ 88 
Table 81: 
Drinks per Week (mITT) – Full Model, Mixed Effects, Weeks 3-6 ................................... 88 
Table 82: 
Drinks per Drinking Day (mITT) – Weeks 3-6 ................................................................... 88 
Table 83: 
Drinks per Drinking Day (mITT) – Full Model, Mixed Effects, Weeks 3-6 ...................... 88 
Table 84: 
Mean Cigarettes Smoked Among Smokers (mITT) – Weeks 3-6 ....................................... 88 
Table 85: 
Mean Cigarettes Smoked Among Smokers (mITT) – Full Model, Mixed Effects, Weeks 3-
6 ........................................................................................................................................... 88 
Table 86: 
PACS (mITT) – Weeks 3-6 ................................................................................................. 88 
Table 87: 
PACS (mITT) – Full Model, Mixed Effects, Weeks 3-6 .................................................... 88 
Table 88: 
Percentage of Subjects Abstinent from Nicotine Use1 Weeks 3-6 – Among Subjects that 
Used Nicotine Products at Baseline..................................................................................... 89 
Table 89: 
Percentage of Subjects Abstinent from Nicotine Use1 Weeks 3-6 – Full Model Logistic 
Regression (Among Nicotine Users at Baseline) ................................................................ 89 
Table 90: 
Percentage of Subjects Abstinent from Smoking Weeks 3-6 – Among Baseline Smokers 90 
Table 91: 
Percentage of Subjects Abstinent from Smoking Weeks 3-6 – Full Model Logistic 
Regression (Among Baseline Smokers) .............................................................................. 90 
Table 92: 
PSQI Scores – mITT Subjects ............................................................................................. 91 
Table 93: 
PSQI Scores (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 ...................................... 91 
Table 94: 
POMS Total Mood Disturbance Score – mITT ................................................................... 92 
Table 95: 
POMS Total Mood Disturbance Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 792 
Table 96: 
POMS Tension-Anxiety Score – mITT Subjects ................................................................ 94 
Table 97: 
POMS Tension-Anxiety Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 .......... 94 


 
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Table 98: 
POMS Anger-Hostility Score – mITT Subjects .................................................................. 94 
Table 99: 
POMS Anger-Hostility Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 ........... 94 
Table 100: 
POMS Vigor-Activity Score – mITT Subjects .................................................................... 94 
Table 101: 
POMS Vigor-Activity Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 ............. 94 
Table 102: 
POMS Fatigue-Inertia Score – mITT Subjects .................................................................... 94 
Table 103: 
POMS Fatigue-Inertia Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 ............. 94 
Table 104 
POMS Confusion-Bewilderment Score – mITT Subjects ................................................... 94 
Table 105: 
POMS Confusion-Bewilderment Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 794 
Table 106: 
POMS Depression-Dejection Score – mITT Subjects......................................................... 94 
Table 107: 
POMS Depression-Dejection Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 .. 94 
Table 108: 
PROMIS Negative Consequences of Alcohol Scores – mITT Subjects ............................. 94 
Table 109: 
ANCOVA PROMIS Negative Consequences of Alcohol – mITT Subjects ....................... 95 
Table 110: 
Overall Summary of Adverse Events – Safety Subjects ..................................................... 98 
Table 111: 
 Number and Percentage of Subjects with Adverse Events - Safety Subjects ..................... 98 
Table 112: 
Summary of Subjects with Adverse Events by Severity and Relationship – ASP8062 .... 100 
Table 113: 
Summary of Subjects with Adverse Events by Severity and Relationship – Placebo ....... 101 
Table 114: 
Number and Percentage of Subjects with Adverse Events by Maximum Severity - Safety 
Subjects ............................................................................................................................. 101 
Table 115: 
Number and Percentage of Subjects Adverse Events by Relatedness - Safety Subjects ... 102 
Table 116: 
Number and Percentage of Subjects with Treatment-Related Adverse Events by Maximum 
Severity- Safety Subjects ................................................................................................... 103 
Table 117: 
Number and Percentage of Subjects with Adverse Events Occurring in >= 5% of Subjects 
in Any One Group - Safety Subjects ................................................................................. 104 
Table 118: 
Number and Percentage of Subjects with Adverse Events Leading to Discontinuation of 
Study - Safety Subjects ...................................................................................................... 104 
Table 119: 
Number and Percentage of Subjects with Adverse Events Leading to Discontinuation of 
Study Drug – Safety Subjects ............................................................................................ 105 
Table 120: 
 CIWA-AR Score > 10 at Least Once During Treatment – Safety Subjects ..................... 105 
Table 121: 
Summary of Vital Signs and Body Weights – Safety Subjects ......................................... 106 
Table 122: 
 Summary of ECG Results - Safety Subjects .................................................................... 106 
Table 123: 
Summary of Blood Chemistries and Hematology – Safety Subjects ................................ 107 
Table 124: 
Summary of Urinalysis Continuous Data – Safety Subjects ............................................. 107 
Table 125: 
Summary of Urine Glucose and Nitrites – Safety Subjects ............................................... 108 


 
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Table 126: 
Summary of Urine Protein, Ketones, Billirubin, Leukocyte Esterace, and Blood – Safety 
Subjects ............................................................................................................................. 109 
Table 127: 
Summary of Positive Urine Drug Tests, Preganancy Test or BAC > 0.02 Any Time During 
the Study– Safety Subjects ................................................................................................ 110 
Table 128: 
Frequency of Subjects with Suicidal Ideation Any Time During the Study – Safety 
Subjects ............................................................................................................................. 111 
Table 129: 
Return to Baseline ACQ-SF-R Scores – Safety Subjects .................................................. 111 
 
 
 
List of Listings 
Listing 1: Subject Disposition - All Subjects ............................................................................................ 114 
Listing 2. Enrollment and Randomization – All Consented Subjects ....................................................... 115 
Listing 3: Reason not Eligible – Screen Failures ...................................................................................... 115 
Listing 4: Protocol Deviations – Safety Subjects ...................................................................................... 115 
Listing 5: Subjects Excluded from the Efficacy Analysis or Evaluable Set ............................................. 117 
Listing 6: Demographics Data – Safety Subjects ...................................................................................... 118 
Listing 7: Baseline Drinking Characteristics – mITT Subjects ................................................................ 118 
Listing 8: Baseline Smoking Characteristics – mITT Subjects ................................................................ 119 
Listing 9: MINI DSM-5 Disorders – Safety Subjects ............................................................................... 119 
Listing 10: MINI DSM-5 AUD – Safety Subjects .................................................................................... 120 
Listing 11: Medical History – Safety Subjects ......................................................................................... 120 
Listing 12: Drinking Goal – mITT Subjects ............................................................................................. 121 
Listing 13: Physical Exam – Safety Subjects ............................................................................................ 121 
Listing 14: Daily and Weekly Standard Drink Units (TLFB) During Treatment – mITT Subjects ......... 122 
Listing 15: Brief Drinking Questionnaire – mITT Subjects ..................................................................... 122 
Listing 16: Cue Reactivity – mITT Subjects ............................................................................................ 122 
Listing 17: Drinking Consequences and Craving Scores – mITT Subjects .............................................. 123 
Listing 18: Pittsburg Sleep Quality Index Scores – mITT Subjects ......................................................... 123 
Listing 19: Smoking and Other Nicotine Use Data– mITT Subjects ........................................................ 124 
Listing 20: MINI AUD– Safety Subjects .................................................................................................. 125 
Listing 21. Exit Interview – mITT Subjects ............................................................................................. 126 
Listing 22: Drug Exposure from AiCure– mITT Subjects ........................................................................ 127 


 
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Listing 23: Drug Accountability – Safety Subjects .................................................................................. 127 
Listing 24: Take Control – mITT Subjects ............................................................................................... 127 
Listing 25: Adverse Events – Safety Subjects .......................................................................................... 129 
Listing 26: Serious Adverse Events – Safety Subjects ............................................................................. 129 
Listing 27: POMS Scores – mITT Subjects .............................................................................................. 131 
Listing 28. Columbia-Suicide Severity Scale – Safety Subjects ............................................................... 132 
Listing 29: Blood Chemistries – Safety Subjects ...................................................................................... 133 
Listing 30: Hematology – Safety Subjects ................................................................................................ 134 
Listing 31: Urinalysis – Safety Subjects ................................................................................................... 135 
Listing 32: Urinalysis Microscopy1 – Safety Subjects .............................................................................. 136 
Listing 33: Pregnancy Test/Birth Control Data – Safety Subjects ............................................................ 137 
Listing 34: Blood Alcohol Concentration – Safety Subjects .................................................................... 138 
Listing 35. Urine Drug Screen – Safety Subjects ..................................................................................... 138 
Listing 36: Vital Signs and Body Weights– Safety Subjects .................................................................... 139 
Listing 37. ECG – Safety Subjects ............................................................................................................ 139 
Listing 38. Prior and Concomitant Medications – Safety Subjects .......................................................... 139 
Listing 39: Blood for Drug Concentrations – Safety Subjects .................................................................. 140 
Listing 40: Comments – Safety Subjects .................................................................................................. 140 
 
 
List of Figures 
Figure 1: 
Percentage of Subjects No Heavy Drinking Days Weeks 3-6 ........................................... 142 
Figure 2: 
Percentage of Subjects Abstinent Weeks 3-6 .................................................................... 142 
Figure 3: 
Weekly Percentage of Subjects No Heavy Drinking Days (mITT) .................................. 142 
Figure 4: 
Weekly Percentage of Subjects Abstinent (mITT) ............................................................ 142 
Figure 5: 
Weekly Percentage WHO 1-Level Decrease in Alcohol Consumption (mITT) ............... 142 
Figure 6: 
Weekly Percentage WHO 2-Level Decrease in Alcohol Consumption No Imputation 
(mITT) ............................................................................................................................... 142 
Figure 7: 
Percentage Days Abstinent per Week Least Squares Means – (mITT) ............................. 142 
Figure 8: 
Percent Heavy Drinking Days per Week Lease Squares Means –(mITT) ........................ 142 
Figure 9: 
Mean Drinks per Week Lease Squares Means – (mITT) .................................................. 142 
Figure 10: 
Mean Drinks per Drinking Day by Week Least Squares Means –  (mITT) ...................... 142 


 
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Figure 11: 
Weekly Number of Cigarettes Smoked in Smokers Over Entire Treatment Period – Least 
Squares Means (mITT) ...................................................................................................... 142 
Figure 12: 
Clinical Chemistry, Urinalysis, and Hematology Values Over Time ............................... 142 
 


 
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1. 
ABBREVIATIONS 
Abbreviation 
Definition 
ACQ-SF-R 
Alcohol Craving Scale – Short Form  
AE 
Adverse event 
AICc 
Akaike Information Criterion corrected for finite samples 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
AUD 
Alcohol Use Disorder 
BAC 
Blood alcohol concentration 
CI 
Confidence interval 
CIWA-AR 
Clinical Institute Withdrawal Assessment for Alcohol-revised 
CrCl 
Creatinine clearance 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CTCAE 
Common terminology criteria for adverse events 
dL 
Deciliter 
DSM-5 
Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDMS 
Electronic Data Management System 
EOS 
End of study 
F 
Fahrenheit 
FDA 
Food and Drug Administration 
g 
Gram 
GGT 
Gamma-glutamyl transferase 
hr 
Hour 
ICH 
International Conference on Harmonization 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
μg 
Microgram 
min 
Minutes 
MINI 
MINI Neuropsychiatric Interview 
mITT 
Modified intention-to-treat 
mL 
Milliliter 
mm 
Millimeter 
NHDD 
No heavy drinking days 
NIAAA 
National Institutes on Alcohol Abuse and Alcoholism 
oz 
Ounce 
PACS 
Penn Alcohol Craving Scale 
POMS 
Profile of Mood State 


 
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Abbreviation 
Definition 
PROMIS 
Patient Reported Outcomes Measurement Information System 
PSNHDD 
Percentage of subjects with no heavy drinking days 
PSQI 
Pittsburg Sleep Quality Index 
PT 
Preferred term 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SDU 
Standard drinking unit 
SOC 
System Organ Class 
THC 
Tetrahydrocannabinol 
TLFB 
Timeline followback  
TSH 
Thyroid-stimulating hormone 
ULN 
Upper limit of normal 
VAS 
Visual analog scale 
WHO 
World Health Organization 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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2. 
INTRODUCTION 
This statistical analysis plan (SAP) for Protocol No. HLAB-003, “Human Laboratory Study of 
ASP8062  for Alcohol Use Disorder” describes and expands upon the analytical plan presented 
in the protocol.  
This document contains all planned analyses, reasons and justifications for these analyses for all 
study data. This plan also includes sample tables, figures, and listings that will be populated. The 
SAP will follow the International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use (ICH) Guidelines as indicated in Topic E3 
(Structure and Content of Clinical Study Reports), Topic E8 (General Considerations for Clinical 
Trials) and Topic E9 (Statistical Principles for Clinical Trials). The structure and content of the 
SAP provides sufficient detail to meet the requirements identified by the FDA and ICH. 
The following sources were used in preparation of this SAP: 
• Protocol # HLAB-003, Protocol Version No.: 6.0; Version Date: 13 Jun 2022 
• ICH Guidance Topics E9, E3 and E8 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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3. 
PROTOCOL SUMMARY 
3.1. 
Study Objectives 
3.1.1. 
Primary 
The primary objective of this study is to evaluate the effects of ASP8062, 25 mg once a day and 
matched placebo, on alcohol cue-elicited alcohol craving during a human laboratory paradigm 
after 2 weeks of daily dosing among subjects with moderate to severe alcohol use disorder 
(AUD) as confirmed by the Diagnostic and Statistical Manual of Mental Disorders – Fifth 
Edition (DSM-5™). 
3.1.2. 
Secondary 
Secondary objectives include evaluation of ASP8062, 25 mg once a day, and matched placebo 
on reduction of alcohol consumption, alcohol craving, cigarette smoking (among smokers) and 
nicotine use (among nicotine users), mood, sleep, alcohol use negative consequences, study 
retention, and safety and tolerability throughout the last 4 weeks of the treatment phase of the 
study. 
3.2. 
Study Design 
This study is a 2-arm, double-blind, randomized, placebo-controlled, parallel group, 3-site study 
designed to assess the effects of ASP8062 as compared with placebo on responses to in vivo 
alcohol cue exposure in the human laboratory setting. After signing informed consent, subjects 
will be screened for eligibility and have other baseline assessments. Screening is permitted over 
a 14-day period and most baseline assessments will be performed on the day of randomization. 
Assessments include alcohol breathalyzer test (before signing consent), medical history, physical 
examination, weight, vital signs, electrocardiogram (ECG), drinking history by the timeline 
follow-back (TLFB) method, Clinical Institute Withdrawal Assessment for Alcohol-revised 
(CIWA-AR), prior medication use, MINI neuropsychiatric interview, urine drug test, smoking 
quantity frequency and nicotine use interview, clinical laboratory tests including chemistry, 
hematology, medical urinalysis, alcohol craving responses during a baseline cue reactivity 
session, Columbia Suicide Severity Rating Scale (C-SSRS), drinking goal, Penn Alcohol 
Craving Scale (PACS), Pittsburg Sleep Quality Index (PSQI), PROMIS Alcohol Negative 
Consequences short form, Profile of Moods State (POMS), Hyperkatifeia Scale and confirmation 
that subjects are treatment seeking and desire a reduction or cessation of drinking. Women of 
child-bearing potential will have a pregnancy test.  
If eligible for the study, 60 subjects will be randomized using a stratified permuted block 
randomization procedure with “clinical site” as the stratification variable in an approximate 1:1 
ratio (targeting 30 subjects per group) to receive either ASP8062 25 mg once daily or matched 
placebo for 6 weeks.  
Subjects will be seen in the clinic at screening, at randomization and 5 other times during the 
study. A final follow-up telephone interview will occur ~2 weeks after the end of study in-clinic 
visit. Two cue reactivity sessions will be conducted. The first will be during screening (named 
pretreatment session) and the second will be after two weeks of investigational product 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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administration at Study Week 3. During these cue sessions, subjects will be presented with 
water, followed by alcohol and will be asked to respond to 4 individual visual analog scales 
(VAS) items assessing alcohol craving and 1 item assessing beverage liking. Other assessments 
during the treatment period include TLFB, clinical laboratory tests, blood for serum levels of 
study drug for determining study drug compliance, vital signs, ECG, concomitant medications, 
CIWA-AR, C-SSRS, pregnancy test, male and female birth control methods, adverse events 
(AEs), PACS, smoking quantity/frequency, PSQI, and POMS. The end of study visit will include 
the other assessments performed during the treatment phase and an Exit Interview, PROMIS 
questionnaire, and a treatment referral. 
Study assessments and procedures will be performed at the visits and time points outlined in the 
Schedule of Assessments (Table 1). 
 


 
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Table 1: 
Schedule of Assessments  
Study Phase 
Screening 
Treatment 
End of 
Studya 
Follow-up 
Call 
Clinic Visit # 
1 
2 
3 
4 
5 
6 
7 
 
Study Week (Days)b 
-2 to -1 
(-14 to -1) 
1 
(1 to 7) 
2 
(8 to 14) 
3 
(15 to 21) 
4 
(22 to 28) 
5 
(29 to 35) 
7 
(43 to 49) 
9 
(57 to 63) 
Informed Consent 
X 
 
 
 
 
 
 
 
Alcohol Breathalyzer 
X 
X 
X 
X 
X 
X 
X 
 
Urine Drug Testc 
X 
X 
X 
X 
X 
X 
X 
 
Locator Form 
X 
Update 
Update 
Update 
Update 
Update 
Update 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical History 
X 
Update 
 
 
 
 
 
 
Physical Exam  
X 
Update 
 
 
 
 
 
 
Body Weight 
X 
 
 
 
X 
 
X 
 
MINI  
X 
 
 
 
 
 
 
 
C-SSRS 
 
X 
X 
X 
X 
X 
X 
 
Clinical Chemistryd 
X 
 
 
 
X 
 
X 
 
Hematologye 
X 
 
 
 
X 
 
X 
 
Medical Urinalysisf 
X 
 
 
 
X 
 
X 
 
Pregnancy Test  
X 
X 
 
 
 
 
X 
 
Birth control methods (all subjects) 
X 
Update 
Update 
Update 
Update 
Update 
Update 
 


 
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Study Phase 
Screening 
Treatment 
End of 
Studya 
Follow-up 
Call 
Clinic Visit # 
1 
2 
3 
4 
5 
6 
7 
 
Study Week (Days)b 
-2 to -1 
(-14 to -1) 
1 
(1 to 7) 
2 
(8 to 14) 
3 
(15 to 21) 
4 
(22 to 28) 
5 
(29 to 35) 
7 
(43 to 49) 
9 
(57 to 63) 
Vital Signsg 
X 
X 
X 
X 
X 
X 
X 
 
Eligibility Checklist 
X 
X 
 
 
 
 
 
 
Drinking Goal 
X 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
X 
 
X 
 
Prior and Concomitant Meds 
X 
X 
X 
X 
X 
X 
X 
X 
CIWA-AR 
X 
X 
X 
X 
X 
X 
X 
X 
Screening Cue Reactivity Session: 
VAS Scales 
X 
 
 
 
 
 
 
 
Randomization 
 
X (Day 1) 
 
 
 
 
 
 
Blood for Drug Concentration 
 
 
 
 
X 
 
X 
 
Drug compliance/ accountability/  
Review AiCure 
 
Dispense 
Day 1 
X 
X 
X 
X 
X 
 
AEs (open ended question) 
 
X 
X 
X 
X 
X 
X 
X 
Brief Telephone Interviewh 
 
once during 
the week 
once during 
the week 
As needed if the subject misses a clinic visit 
 
Take Control 
 
X 
X 
X 
Xi 
X 
X 
 
Treatment Cue Reactivity Session: 
VAS Scales 
 
 
 
X 
 
 
 
 


 
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Study Phase 
Screening 
Treatment 
End of 
Studya 
Follow-up 
Call 
Clinic Visit # 
1 
2 
3 
4 
5 
6 
7 
 
Study Week (Days)b 
-2 to -1 
(-14 to -1) 
1 
(1 to 7) 
2 
(8 to 14) 
3 
(15 to 21) 
4 
(22 to 28) 
5 
(29 to 35) 
7 
(43 to 49) 
9 
(57 to 63) 
TLFB 
X 
X 
X 
X 
X 
X 
X 
 
Brief Drinking Questionnaire 
as needed 
 
 
 
 
 
 
 
Exit Interview 
 
 
 
 
 
 
X 
 
ACQ-SF-R 
2X pre/post 
cue session 
 
 
2X pre/post 
cue session 
 
 
 
 
PACS 
 
X 
X 
X 
X 
X 
X 
 
Cigarette smoking 
quantity/frequency and nicotine use 
 
X 
 
 
 
X 
X 
 
PSQI 
 
X 
 
 
 
X 
X 
 
POMS 
 
X 
 
 
 
X 
X 
 
PROMIS Alcohol Negative 
Consequences 
 
X 
 
 
 
 
X 
 
Hyperkatifeia Scale 
 
X 
 
 
 
 
 
 
Treatment Referral 
 
 
 
 
 
 
X 
 
Follow-Up Telephone Interview 
 
 
 
 
 
 
 
X 
Final Subject Disposition 
 
 
 
 
 
 
 
X 
 
a 
EOS - end of study. These assessments are to be done at Week 7 or if the subject discontinues early and agrees to a final clinic visit. 
b 
Within each study week, there should be a least two days elapsed since the visit in the prior week. 


 
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c 
Test for opiates (i.e., morphine test), cocaine, amphetamines, methamphetamine, THC, buprenorphine, methadone, benzodiazepines, oxycodone, 
barbiturates, 3,4-methylenedioxy-methamphetamine (MDMA – also known as ecstasy), and EtG. 
d 
Creatinine, urea nitrogen, total bilirubin, ALT, AST, alkaline phosphatase, GGT, albumin, total cholesterol, triglycerides, sodium, potassium, and chloride 
e 
Complete blood cell count including RBC, WBC, hemoglobin, hematocrit, and platelets. 
f 
A dipstick urinalysis will be performed that tests for specific gravity, ketones, pH, protein, blood, glucose, nitrites, bilirubin, and leukocyte esterase. If the 
dipstick is positive for blood, leukocyte esterase, or protein, then a microscopic analysis will be performed at the discretion of the investigator. 
g 
Sitting blood pressure and heart rate. 
h 
Telephone calls after the Week 1 and 2 in clinic visits will collect AEs, concomitant medications, CIWA-AR, and give a drug compliance reminder. The call 
during Week 2 should be several days before the cue session to remind the subject of the planned visit. 
i 
Two modules will be viewed this week. 
 


 
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3.3. 
Study Endpoints 
3.3.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the “strength” of alcohol craving VAS score (item 1 below) 
upon presentation of the first alcohol cue at Week 2 – after one week of investigational product 
treatment. 
Confirmatory secondary endpoints include the VAS score for the other 3 VAS scales (items 2 
through 4 below) for the first alcohol cue and the average score of the 4 VAS craving items; and 
the difference score (alcohol craving VAS scores minus the water craving VAS score). 
Tbeverage liking VAS item is also a confirmatory secondary endpoint. The 4 VAS craving items 
in the order of presentation are: 
1. How strong is your craving to drink alcohol? - note this is the primary efficacy endpoint. 
2. Having a drink would make things just perfect. 
3. If I could drink alcohol now, I would drink it. 
4. It would be hard to turn down a drink right now. 
The beverage liking item is: How much did you like the beverage just given to you? 
3.3.2. 
Secondary Efficacy Endpoints 
Secondary efficacy endpoints will be analyzed over the last 4 weeks of the treatment period of 
treatment. 
1. Percentage of subjects with no heavy drinking days. A “heavy drinking day” is 4 or more 
drinks per drinking day for women and 5 or more drinks per drinking day for men. 
2. Percentage of subjects abstinent from alcohol 
3. Percentage of subjects with at least a WHO 2-level decrease in alcohol consumption 
4. Percentage of subjects with at least a WHO 1-level decrease in alcohol consumption 
5. Percentage of days abstinent per week 
6. Percentage of heavy drinking days per week 
7. Percentage of very heavy drinking days per week. A “very heavy drinking day” is 8 or 
more drinks per drinking day for women and 10 or more drinks per drinking day for men. 
8. Weekly mean number of drinks per week 
9. Weekly mean drinks per drinking day 
10. Cigarettes smoked per week among smokers 
11. Percentage of subjects with no nicotine use among those reporting nicotine use at 
baseline 
12. Alcohol craving score (PACS) 
13. Sleep quality (PSQI) score 


 
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14. Profile of Mood States (POMS) score 
15. PROMIS Alcohol Negative Consequences Score 
3.3.3. 
Safety Endpoints 
1. Vital signs 
2. Body weight 
3. Clinical laboratory parameters 
4. BAC by breathalyzer 
5. Urine drug tests 
6. AEs  
7. ECG results 
8. CIWA-AR scores 
9. Frequency of subjects with suicidal ideation at any time during the treatment period 
(C-SSRS) 
10. Concomitant medication use 
11. ACQ-SF-SR score (pre- and post-cue response sessions) 
3.3.4. 
Compliance 
Compliance will be assessed using the AiCure smart phone application and by tablet counts of 
returned blister packs at regular clinic visits. In addition, blood will be collected to determine 
plasma levels of ASP8062 and its metabolites. Compliance will be calculated as the percentage 
of investigational products taken as prescribed and by the total amount of study drug consumed. 
Participation in study visits will be evaluated as the percentage of subjects with complete 
drinking data. Compliance determined by ASP8062 plasma levels will be reported as number 
and percentage of subjects with a level above the limit of detection at each time point. 
 


 
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4. 
DEFINITION OF ANALYSIS SETS 
The study analysis populations will consist of the following: 
Modified Intention-to-Treat (mITT) Analysis Set: The mITT set is defined as subjects 
randomized to participate in the study that took at least one dose of investigational product and 
had a non-missing VAS craving primary endpoint. 
Evaluable Analysis Set: The evaluable analysis set for the secondary endpoints is defined as 
those subjects randomized to the study who took at least 1 tablet per day for at least 80% of days 
in Weeks 1-6.  
Safety Analysis Set: The safety analysis set includes all subjects who took at least one dose of 
investigational product. 
The analysis of the primary and confirmatory efficacy endpoints will be conducted on both the 
mITT and evaluable analysis sets. All secondary endpoint analyses will be performed on the 
mITT set. Weekly percentage heavy drinking days, mean number of drinks per week, and PACS 
scores will also be performed on the evaluable analysis set. Safety analyses will be conducted on 
the safety analysis set. 


 
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5. 
ASSSESSMENT AND JUSTIFICATION OF STUDY ENDPOINTS 
5.1. 
Alcohol Craving Visual Analog Scales 
Alcohol craving in response to a water and typical alcohol beverage cue is assessed using 4 
individual VAS items adapted from the ACQ (Singleton-1994).  
The VAS craving scale items include in the following order: 
1. How strong is your craving to drink alcohol? 
2. Having a drink would make things just perfect. 
3. If I could drink alcohol now, I would drink it. 
4. It would be hard to turn down a drink right now. 
Anchors (scores) for items 1, 3, and 4 are: Strongly Disagree (0) to Strongly Agree (20). 
Anchors (scores) for question 2 are: None (0) to Extremely Strong (20). 
There will be no imputation for missing values. 
5.2. 
Alcohol Consumption Endpoints 
5.2.1. 
Daily Quantity of Alcohol Consumption 
Drinking will be assessed using the TLFB methodology and Form 90 structured assessment 
pattern chart. The TLFB is a semi-structured interview that provides estimates of the daily 
quantity of alcohol consumption during specified time periods. It uses a calendar prompt and a 
number of other memory aids (e.g., holidays, payday, and other personally relevant dates) to 
facilitate accurate recall of drinking or other drug use during the target period. The procedure has 
been widely used in clinical and research contexts. It has demonstrated adequate levels of 
reliability and validity when administered as an in-person interview, over the telephone, and 
when administered via computer (Carey-1997, Sobell et al-1988, Sobell et al-1996). 
If a subject is withdrawn from the study early and is no longer participating in clinic visits or 
providing TLFB drinking data but is willing to be contacted by phone at the week most proximal 
to dropout, then they will be asked about any drinking and heavy drinking during the time since 
last contact. Phone calls will continue until the end of the treatment period, as deemed acceptable 
by the patient. The two questions cover whether the subject had any heavy drinking days or 
drinking days during the period covered and will be used to capture drinking data in the absence 
of individual daily TLFB drinking data. 
5.2.2. 
Drinking Days 
A drinking day is one calendar day in which the subject reported any alcohol consumption (i.e., 
> 0 standard drinking units [SDUs]). A standard drink contains approximately 0.6 fluid ounces 
(oz) of pure alcohol. The data given by the subjects on amount and type of alcoholic beverage(s) 
consumed will be converted to SDUs. Standard drink unit definitions are provided in Table 2. 
 


 
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Table 2: 
Standard Drink Unit Definitions 
For Beer (~ 5% alcohol), the approximate number of SDUs in: 
• 12 oz = 1.0 
• 16 oz = 1.3 
• 24 oz = 2.0 
• 40 oz = 3.3 
For malt liquor (~ 7% alcohol), the approximate number of SDUs in: 
• 12 oz = 1.4 
• 16 oz = 1.9 
• 22 oz = 2.6 
• 40 oz = 4.7 
For table wine (~ 12% alcohol), the approximate number of SDUs in: 
• 750 mL bottle = 25oz = 5.0 
• 5 oz glass = 1.0 
• 10 oz glass = 2.0 
For 80 proof spirits (~ 40% alcohol), or hard liquor, the approximate number of 
SDUs in: 
• 1.5 oz (mixed drink) = 1.0 
• 16 oz (pint) = 8.5 
• 25 oz (a fifth) = 17.0 
• 1.75 L (59 oz) = 39.0 
5.2.3. 
Very Heavy and Heavy Drinking Day 
A very heavy drinking day is defined as 8 or more drinks per day for a woman, and 10 or more 
for men. A heavy drinking day is defined as a day with 5 or more drinks (SDUs) for males and 4 
or more drinks (SDUs) for females.  
5.2.4. 
Days at Risk 
If a subject is being treated at an inpatient facility, is incarcerated, or otherwise under 
confinement, the days spent in under these conditions is considered a reduction in the days at risk 
for drinking and is deducted from the denominator in calculations of rates of drinking days. 
5.2.5. 
Percentage of Subjects with No Heavy Drinking Days and Percentage of 
Subjects Abstinent from Alcohol 
The percentage of subjects with no heavy drinking days is the number of subjects that have no 
heavy drinking days during the period of interest divided by the number of subjects with at least 
one day of non-missing drinking data during the period of interest, multiplied by 100.  
The percentage of subjects abstinent from alcohol is calculated similarly, except the numerator is 
the number of subjects that have no drinking days during the period of interest. 


 
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5.2.6. 
Weekly Percentage of Heavy Drinking Days and Weekly Percentage of Days 
Abstinent 
Weekly percentage of heavy drinking days is the number of heavy drinking days in a 7-day 
period divided by 7 then multiplied by 100. The TLFB permits capturing data in a subsequent 
visit if a visit is missed; however, if fewer than 7 days are observed then the denominator is the 
number of days observed in the 7-day period. At least 3 days in a week must be observed; 
otherwise, the week is considered missing. 
Weekly percentage of days abstinent is similarly calculated by using the number of days 
abstinent instead of the number of heavy drinking days. 
5.2.7. 
Weekly Mean Number of Drinks and Weekly Mean Number of Drinks per 
Drinking Day 
Weekly mean number of drinks is the sum of SDUs calculated to the tenths over 7 calendar days 
divided by the number of days with non-missing data. The quotient is multiplied by 7. At least 3 
days in a week must be observed; otherwise, the week is considered missing.  
Weekly mean number of drinks per drinking days utilizes the same numerator, and the 
denominator is the number of days with greater than 0 SDUs. Weeks where all days within the 
week are abstinent are assigned a value of 0 for weekly drinks per drinking day.  
5.2.8. 
World Health Organization Drinking Risk Categorical Scale 
The WHO has developed a drinking risk categorical scale that can be used in a responder 
analysis approach to assess clinically relevant decreases in alcohol consumption (Aubin et al-
2015). Two dichotomous endpoints will be analyzed: WHO 1-level and WHO 2-level decrease 
in alcohol consumption. The WHO 1-level and 2-level decrease endpoints are the percentage of 
subjects experiencing at least a 1-level or 2-level decrease in WHO levels of alcohol 
consumption, respectively, from the level at baseline (the period including the 28 days before 
screening) to the level during the last 4 weeks of the maintenance phase (Study Weeks 2-5). The 
WHO levels of average alcohol consumption per day are as follows: 
              
 
Males              Females 
Low Risk       
1 to 40g            1 to 20g 
Medium Risk    41 to 60g          21 to 40g 
High Risk      
61 to 100g       41 to 60g 
Very High Risk  101+g               61+g 
where 14g = 1 SDU (WHO-2000). In computing the alcohol consumption level, average drinks 
per day will be used, computed as the sum of all drinking in the 28 day period divided by the 
number of days with non-missing drinking data in that period. Abstinent subjects will be 
included in a separate “Abstinent” category. A subject must have at least 1 week of data during 
the last 4 weeks of the maintenance phase to be considered non-missing. 
5.3. 
Alcohol-Related Craving, Consequences, and Withdrawal 
Alcohol-related craving is measured using the ACQ-SF-R scale and PACS; alcohol-related 
consequences are measured using the PROMIS Alcohol Negative Consequences scale; and 
alcohol-related withdrawal is measured using the CIWA-AR scale. The PACS and PROMIS 


 
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Alcohol Negative Consequences are used as efficacy endpoints, while the ACQ-SF-R and 
CIWA-AR scales are safety endpoints. 
The ACQ-SF-R contains 12-items adapted from the 47-item ACQ-NOW developed by Singleton 
et al (1994) to assess craving for alcohol among alcohol users in the current context (right now). 
Items 3, 8, and 11 are reverse keyed. A general craving index is derived by summing all items 
and dividing by 12. If an item is missing, then the number of items is reduced by the number 
missing, and the sum is only the sum of the answered items. At least 10 items must be endorsed 
for the general craving index of ACQ-SF-R to be considered non-missing (i.e., scored).  
The PACS is a five-item self-administered instrument for assessing craving (Flannery-1999). 
Frequency, intensity, and duration of thoughts about drinking are assessed along with ability to 
resist drinking. The final item asks the responder to provide an average rating of his/her craving 
over the course of the past week. The questions on the PACS use descriptors coupled with 
numerical ratings ranging from 0 to 6. The items are summed for a total score. 
PROMIS Alcohol Negative Consequences scale is for negative consequences from alcohol use. 
The short form of the PROMIS Alcohol Negative Consequences questionnaire will be used to 
assess outcomes of alcohol use over the past 30 days (Pilkonis-2013).  
The 7 PROMIS items include:  
• Drinking created problems between me and others 
• I disappointed others when I drank 
• I was unreliable after I drank 
• Others complained about my drinking 
• I used poor judgment when I drank 
• I said or did embarrassing things when I drank 
• I had trouble getting things done after I drank 
Each item is rated on a 5 point scale including: Never (1), Rarely (2), Sometimes (3), Often (4),  
and Almost Always (5) for the past 30 days. A subject’s total score is converted to a T-score 
using scoring table provided by NIH PROMIS. 
The CIWA-AR modified telephone version is an adaptation for telephone administration of the 
CIWA-AR a brief 10-item measure used to provide a quantitative index of the severity of the 
alcohol withdrawal syndrome (Sullivan et al-1989). The CIWA-AR has been used both in 
clinical and research applications and has demonstrated both reliability and validity (Sellers et 
al-1992, Stuppaeck et al-1994). The total score is the sum of the individual item scores. Since 
this is an interview scale, no missing items are anticipated. A score ≥ 10 is considered an 
indication that the subject is undergoing alcohol withdrawal. 
5.4. 
Mood 
Mood will be measured with the POMS, while negative emotional state will be measured using 
an exploratory measure of hyperkatifeia. 


 
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The POMS measures dimensions of affect or mood (McNair and Heuchert-2005). It consists of 
65 adjectives to which the subject responds according to a 5-point scale ranging from “not at all 
(0)” to “extremely (5).” Six subscale scores will be computed for items grouped as follows: 
Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and 
Confusion-Bewilderment. A Total Mood Disturbance score will also be computed which consists 
of the sum of Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue-Inertia, and 
Confusion-Bewilderment scores then subtracting the Vigor-Activity subscale score. A missing 
value within a subscale will be replaced by the average score of the answered items within the 
subscale; if 2 or more items within a subscale are missing then the entire subscale is missing 
(Macefield et al-2010).  
Hyperkatifeia is defined as a greater intensity of negative emotional/motivational signs and 
symptoms during withdrawal from drugs of abuse in the withdrawal/negative affect stage of the 
addiction cycle (Koob-2021). Hyperkatifeia or negative emotional state is considered to be one 
of stages of addiction in the context of drug withdrawal (Koob and LeMoal-1997, Koob-2019). 
NIAAA has developed a 24-item self-report Hyperkatifeia Scale to capture negative emotionality 
after stopping alcohol drinking that will be assessed for the first time in this study of heavy 
drinkers with a diagnosis of moderate to severe AUD. The items address four measures 
associated with negative emotional state including stress/anxiety, depression, stress, irritable and 
pain.  
One difference between this scale and other negative emotional state scales is the pain questions. 
Pain may be particularly important in AUD as there is a positive association between pain 
severity and a higher risk for AUD (Lawton and Simpson-2009, Edlund et al-2013). Also, 
physical pain appears to be a significant predictor of alcohol use and heavy alcohol use and 
relapse to drinking after a period of abstinence (Larson et al-2007, Caldeiro et al-2008, 
Witkiewitz et al-2015). 
5.5. 
Sleep Quality 
Sleep quality will be measured using the PSQI. The PSQI is a 19-item questionnaire (Buysse et 
al-1989). The addition of all the scores permits an analysis of the subject’s overall sleep 
experience in the past 30 days. The lower the overall score, the better the person sleeps. A score 
≥ 5 is indictive of a sleep disturbance. If any of the items is missing, then the entire form is 
missing for that evaluation (PSQI website). 
5.6. 
Cigarette Smoking Quantity-Frequency and Nicotine Use Questionnaire 
A smoking quantity frequency and nicotine use interview will include 3 questions to assess 
nicotine use via cigarette smoking or via other products during the study: 1) Over the past week, 
on how many days did you smoke cigarettes?; 2) On the days you smoked during the past week, 
how many cigarettes did you smoke on average?; and 3) Over the past week, on how many days 
did you use other nicotine products (ex. chew, cigars, cigarellos, e-cigarettes, vape, gum, patch, 
etc...)? At baseline subjects that answer “0” to question #1 are considered non-smokers for the 
study. Cigarettes per week is the answer to question #1 multiplied by the answer to question #2. 
At baseline, subjects who report smoking (question #1) or the use of other nicotine product 
(question #3) will be considered nicotine users. The responses to questions #1 and #3 will be 


 
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used to calculate the percentage of subjects abstinent from nicotine use among nicotine users. No 
imputation for missing values will be used. 


 
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6. 
HYPOTHESES TO BE TESTED 
6.1. 
Primary Efficacy Endpoint 
Subjects treated with ASP8062 will report significantly lower VAS alcohol craving ratings in 
response to the in vivo alcohol cue during the treatment human laboratory cue session than 
placebo-treated subjects. 
The hypotheses for the confirmatory secondary endpoints for the cue reactivity sessions are the 
same as for the primary endpoint.  
6.2. 
Secondary Efficacy Endpoints 
It is hypothesized that, during the last 4 weeks of the treatment period, ASP8062 as compared to 
the placebo, will: 
1. Increase the percentage of subjects with no heavy drinking days. A “heavy drinking day” 
is 4 or more drinks per drinking day for women and 5 or more drinks per drinking day for 
men. 
2. Increase the percentage of subjects abstinent from alcohol 
3. Increase the percentage of subjects with at least a WHO 2-level decrease in alcohol 
consumption 
4. Increase the percentage of subjects with at least a WHO 1-level decrease in alcohol 
consumption 
5. Increase the percentage of days abstinent per week 
6. Decrease the percentage of heavy drinking days per week 
7. Decrease the percentage of very heavy drinking days per week 
8. Decrease the weekly mean number of drinks per week 
9. Decrease the weekly mean drinks per drinking day 
10. Decrease the weekly mean cigarettes smoked per week among smokers 
11. Increase the percentage of subjects abstinent from nicotine use among subjects who used 
any nicotine products in the week before randomization 
12. Decrease the mean alcohol craving score (PACS) 
13. Decrease the mean PSQI score 
14. Decrease total mood disturbance (POMS) 
15. Decrease in alcohol negative consequences (PROMIS) 
 
 


 
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7. 
SAMPLE SIZE CONSIDERATIONS 
Analysis of covariance with clinical site and baseline cue as the covariates will be used to model 
the primary outcome – the VAS craving score for the alcohol cue. Statistical power was 
estimated using [PASS 13] with the following parameters. The treatment effect parameter—a 
maximal 3-point study drug-placebo difference on the strength of VAS craving in response to the 
alcohol cue—was obtained from Roberts (2017), which used a similar cue reactivity paradigm. 
The mean values on this outcome at Week 3 are assumed to be 11 for ASP8062 and 14 for 
placebo and a standard deviation between subjects of 4. Clinical site and the baseline VAS 
craving for the alcohol cue were assumed to have correlations of 0.13 and 0.39, respectively, 
with the primary outcome. These correlations, coupled with assumed standard deviations for site 
and baseline VAS craving for the alcohol cue of 0.82 and 4, respectively, yield explained 
variation of 26%. These assumptions, with a sample size of 30 subjects per arm (60 total 
subjects), provides 87% statistical power with a 0.05 two-sided significance level. 


 
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8. 
DATA QUALITY ASSURANCE 
Data quality assurance will start with training of clinical investigative staff on data collection and 
assessment procedures including a Manual of Operations that describes what data to collect and 
procedures for completion of eCRFs. Completed eCRFs will be reviewed by Fast-Track Drugs 
and Biologics clinical monitors on a regular basis throughout the trial by comparison against the 
source documents. 
Study data will come from the eCRFs, TLFB spreadsheets, coded AEs, coded medical history, 
AiCure Drug Compliance system outputs, and PK drug levels from the PK lab spreadsheets. 
eCRFs for this study were created using an electronic data management system (EDMS) based 
on IBM clinical development system. eCRFs were created using an established data dictionary 
for each variable including the field name, field type, field attributes, and coding for variables. 
Range checks, alpha-numeric requirements, and null/not null parameters were programmed as 
applicable. The back end database application is Oracle. Data entered into the EDMS system will 
be reviewed by Fast-Track clinical monitors and data managers. If incomplete or inaccurate data 
are found, the data will be queried in the system for site staff to address. The site will resolve 
data inconsistencies and errors using the EDMS with full audit trail of corrections being 
maintained within the system. Corrections and changes to the data will be reviewed by Fast-
Track clinical monitors and data managers. TLFB spreadsheets have a double data entry check 
system and additionally, Fast-Track staff will verify the data entries with the drinking calandar to 
verify the correct percentages of alcohol by volume. QA review of laboratory data outputs is the 
responsibility of the individual testing laboratories; however, Fast-Track staff will verify that 
there is a result reported for each specimen that was recorded in the database as being collected. 
Coded AEs and medical history terms will be cross checked by a second trained MedDRA coder. 
Additional edit checks will be written to detect anomalies in the database. These checks will 
address inconsistencies (within visits, across visits), invalid/unusual values, missing values, and 
protocol violations. Edit checking will be validated on test data or actual clinical trial data. In 
addition to programmed edit checks, quality control examination of data will also be performed 
on reviews of data listings. 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
General Considerations 
For descriptive purposes, dichotomous and categorical variables will be presented as number of 
observations and percentages; continuous variables will be given as means, standard deviations 
(SD), median, miniumum (min) and maximum(max). Statistical tests will be two-tailed at a 0.05 
Type I error rate. P-values for the primary and secondary endpoints of < 0.05 will be considered 
statistically significant. Endpoint data will also be screened for outliers and skewness. 
Appropriate non-parametric tests will be used to compare treatment groups on continuous 
baseline characteristics that are not normally distributed. Continuous endpoint data that are not 
normally distributed will be transformed using either a square root, logarithmic, or inverse 
transformation, the selection of which is determined by skewness and kurtosis statistics with 
values closest to zero. Cohen’s d will be used to calculate the effect size for means and Cohen’s 
h or odds ratios will be used to calculate the effect size for proportions. Descriptive statistics – 
mean, SD, median, min and max – of all endpoint data will be provided for each assement point 
or summarized at each week for drinking endpoints. All data will be presented in listings. 
9.2. 
Participant Accountability and Protocol Deviations 
A summary will be prepared to show dropouts/retention over time in each group, along with the 
reason for early discontinuation. The number of missing observations will be presented between 
groups. Protocol deviations will be presented as summaries by type of deviation. 
9.3. 
Demographics and Other Baseline Characteristics 
Summaries of the characteristics of the subjects in each of the study groups at baseline will be 
prepared for the mITT, and evaluable analysis sets. Demographic characteristics (e.g., age, 
gender, race, and ethnicity) and other baseline characteristics, coded medical history terms, 
screening cue session VAS scale scores and ACQ-SF-R pre and post session score, mood scales 
(e.g., POMS total and subscale scores), Hyperkatifeia Scale scores, PSQI, and drinking goal, 
MINI AUD scores and other DSM-5 diagnoses will be summarized by treatment group for the 
mITT and evaluable subjects. Chi-square tests or t-tests will be used on baseline characteristics 
to test the hypothesis of effective randomization. Imbalance in any of these factors is an 
indication of ineffective randomization which may bias the results observed on any of the 
endpoints. 
Baseline drinking parameters in the 28-days prior to the start of screening, will be summarized 
by treatment group for the mITT subjects. t-tests will be used for baseline drinking paramenters 
to test the hypothesis of effective randomization. The number and percentage of subjects with 
mild, moderate and severe symptoms of AUD and summary statistics for total number of 
symptoms will also be presented. 
The quantity of cigarettes smoked per week in the week prior to randomization will be presented 
for those subjects who reported any smoking. The numbers and percentages of subjects who 
report other nicotine product use at baseline, any nicotine use, and who test positive for THC will 
also be presented. Because smoking, any nicotine use, and positive THC are subsets and are not 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
33  
controlled by randomization, balance across treatment groups will be assessed using t-test and 
chi-square tests. 
Baseline drinking-associated consequences (CIWA-AR and PROMIS Alcohol Negative 
Consequences scores) and drinking-associated-craving (PACS) total score and subscales will be 
summarized in the tables. t-test will be used to test for balance across the treatment groups and 
evaluate the hypothesis of ineffective randomization. 
Continuous variables will be summarized using means, standard deviations, medians, minimum, 
and maximum values. Categorical variables will be summarized using counts and percentages. 
9.4. 
Efficacy Analysis 
9.4.1. 
Primary Analysis of the Primary Efficacy Endpoint 
Each subject will have an initial alcohol cue for “strength” of craving score from the VAS that is 
the primary endpoint. Analysis of covariance (ANCOVA) with the ”strength” of alcohol craving 
value as the dependent variable and the pretreatment “strength’ of alcohol craving score from the 
alcohol cue as an independent fixed effect. Treatment and clinical site will also be included as 
independent factors.  
No imputation for missing endpoint data will be performed. 
9.4.2. 
Confirmatory Secondary Endpoints 
There are 3 additional VAS craving questions and a beverage liking question asked during the 
human lab session. Each of these questions will be analyzed in the same manner as listed in 
Section 9.4.1. An overall mean of the 4 VAS craving items will also be analyzed similarly for 
just the alcohol beverage cue. The difference between the alcohol cue and water cue for each 
VAS item will be computed at both the pre and post treatment time points. The difference values 
for each VAS item and the average difference will be analyzed similarly to the primary endpoint.   
9.4.3. 
Analysis of the Secondary Efficacy Endpoints 
Secondary efficacy endpoints will also be analyzed based on data collected during the last 4 
weeks of the maintenance period (Weeks 3 through 6), including TLFB and other questionnaire 
data assessed at Week 7 that reflect data collected during this period. Note that the data collected 
at Week 7 reflect drinking and other questionnaire items that occurred during Week 6. 
In general, every continuous secondary efficacy endpoint is analyzed using a repeated measures 
mixed effects model where subjects are random effects; factors and covariates are fixed effects. 
The analyses will be performed using SAS PROC MIXED procedure. The information criterion 
is requested from every mixed effects model. Subjects are treated as a class variable and not 
continuous. The week (Weeks 3 through 6), treatment group, and clinical site are also treated as 
class variables. 
The primary analysis model for all continuous endpoints is: 
• Appropriately transformed endpoint = treatment + week + treatment*week + clinical site 
+ baseline equivalent of endpoint + other covariates (identified in Section 9.4.4) 
This model will also be created for the untransformed endpoint. The solution statement from 
SAS PROC MIXED is requested to provide the solution for the fixed effects parameters. A 


 
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34  
REPEATED statement specifies that values are repeated each week and subjects are nested 
within treatment group. The covariance structure is specified.  
The selection of the covariance structure is performed using a simple repeated mixed effects 
model that includes treatment group as the only fixed effect and subject nested within treatment 
group as the only random effect. The covariance structure for each continuous secondary 
endpoint is selected from autoregressive, compound symmetry, Toeplitz, and unstructured. The 
Akaike Information Criterion (AICc) corrected for a finite sample is obtained from each of the 
four models for the four possible covariance structures to determine model fit. The smallest 
(minimum) AICc associated with one of the covariance structurs is selected and the difference 
for each of the other three covariance structures are calculated. A graph is produced of the model 
fit statistics and relative difference for the four possible covariance structures. The graphs across 
the continuous endpoints are compared to determine which covariance structure will be selected 
for all continuous endpoints or if one or more models need different covariance structures. 
Results based on the primary analysis model and the model of the untransformed endpoint will 
be presented in tabular form. The overall least squares means and least square means for each 
time point along with the 95% confidence intervals (CI) will be presented for the untransformed 
endpoint only, while two-tailed p-values and Cohen’s d will be presented for both the 
untransformed and transformed data. Inference and Cohen’s d will be based upon the results 
using appropriately transformed data. Graphs of all secondary endpoints will be produced.  
9.4.3.1. 
Secondary Drinking Endpoints 
Percentage of days abstinent per week, percentage of subjects abstinent, percentage of heavy 
drinking days per week, percentage of very heavy drinking days, weekly mean number of drinks 
per week, and weekly mean number of drinks per drinking day will be analyzed using the mixed 
effects model specified in Section 9.4.3. Covariates for these models will be identified as in 
Section 9.4.4.  
Percentage of subjects with a WHO 1-level decrease, and WHO 2-level decrease in alcohol 
consumption risk category will be analyzed during the last 4 weeks of the maintenance period 
(Weeks 2 through 5) using a logistic regression model. Covariates for the logistic regression will 
be identified as in Section 9.4.4. 2x2 contingency tables will report the WHO 1-level decrease, 
and WHO 2-level decrease along with Cohen’s h, odds ratios and 95% CIs. The Wald statistic 
will be used to test for treatment differences. 
No adjustment for multiple comparisons and no imputation will be used for these endpoints. 
9.4.3.2. 
Alcohol Consequences and Craving Scales 
The PACS is assessed weekly and will be analyzed similarly to the drinking endpoint (Section 
9.4.3.1). PROMIS alcohol negative consequences scale is assessed at baseline and Study Week 7 
which will be used for the secondary endpoint. Analysis of covariance will be used to analyze 
the PROMIS scale similarly to the primary endpoint (Section 9.4.1). 
No imputation or multiplicity adjustment will be used for this endpoint.  


 
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9.4.3.3. 
Smoking and Any Nicotine Use  
The mean number of cigarettes smoked in the past week is measured weekly. The sample is the 
mITT subjects who smoked at baseline. The data will be analyzed as described in Section 9.4.3. 
Covariates for this endpoint will be identified in Section 9.4.4. Amount of other nicotine 
products is not captured, only number of days of use of other nicotine products. The analysis of 
days of use in subjects using other nicotine products at baseline will use the same method as 
cigarettes smoked. In addition, 2 tables will examine the number of subjects that are abstinent 
from cigarettes and any nicotine product use. There will be one logistic regression, if there are 
sufficient number of subjects abstaining from nicotine use, with abstaining as the dependent 
variable and covariates as described in Section 9.4.4. No imputation will be used for these 
endpoints. 
9.4.3.4. 
Sleep and Mood Scales 
The PSQI total score, POMS 6 subscales and total disturbance score are continuous variables. 
The data will be analyzed as described in Section 9.4.3. Covariates for these models will be 
identified as in Section 9.4.4.  
No imputation or multiplicity adjustment will be used for these endpoints. 
9.4.4. 
Covariate Adjustment for the Analysis of Secondary Efficacy Endpoints 
Covariates for continuous secondary efficacy endpoints include the baseline equivalent of the 
endpoint, clinical site, treatment, time and the treatment by time interaction. Additional 
covariates for the secondary efficacy endpoints may include baseline characteristics with a 
theoretical and/or empirical basis for a relationship with a particular secondary endpoint. Such 
characteristics may include, but are not limited to, drinking goal (stop drinking versus reduce 
drinking but not stop), age, and baseline alcohol craving scale total score. Prior to the unblinding 
of the data, matrices of correlations between these baseline characteristics and each of the 
secondary efficacy endpoints, pooled across blinded treatment assignment, will be produced 
(using Pearson for continuous variables, Spearman for categorical outcomes). Selection of 
baseline variables to include as covariates in the models will be based on consideration of the 
following criteria: at least modest correlation with outcome (i.e., r>0.20) and clinical expertise. 
Each endpoint may have a unique set of covariates. Care is taken to only select a limited number 
of covariates such that the models are not over fitted. 
Covariates for the dichotomous secondary endpoints, percentage of subjects abstinent, WHO 1-
level risk category decrease, and WHO 2-level risk category decrease in alcohol consumption, 
will use phi correlation with dichotomous variables, chi-square statistic for categorical variables, 
and biserial correlation. Fewer covariates for the logistic regression may be used depending upon 
the number of events. If the number of events permits the inclusion of a baseline drinking 
covariate, the percentage of days abstinent will be used as the covariate for the percent subjects 
abstinent endpoint and the percent heavy drinking days will be used as the covariate for the 
percent subjects with no heavy drinking days endpoint; however, no baseline drinking covariate 
will be employed for the endpoint, percent subjects with a WHO decrease in alcohol 
consumption, as this endpoint already adjusts for baseline drinking in its calculation. 


 
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9.5. 
Handling of Missing Data 
The primary endpoint of craving cannot be imputed; likewise, for the other craving questions 
given during the human lab session. Secondary endpoints analyzed with mixed effects or logistic 
regression models are capable of handling missing data, so no imputation will be utilized. 
PROMIS scores are analyzed using ANCOVA which cannot handle missing data; therefore, only 
subjects with an assessment during the treatment period will be used and no imputation. 
9.6. 
Safety Analysis 
9.6.1. 
Adverse Events 
AEs will be coded using the most recent version of the Medical Dictionary for Regulatory 
Activities (MedDRA) and will be grouped by system, organ, and class (SOC) and preferred term 
(PT) designation. The severity, frequency, and relationship of AEs to investigational product will 
be presented by SOC and PT groupings. Listings of each individual AE including start date, stop 
date, severity, relationship, outcome, and duration will be provided. Each AE (based on PT) will 
be counted once only for a given study subject. If the same AE occurred on multiple occasions, 
the highest severity will be assumed. Thus, study subjects are not counted multiple times in a 
given numerator in the calculation of frequencies for a specific AE. C-SSRS reports of 
suicidality or suicidal ideation will be reported as AEs and analyzed as AEs if the investigator 
determines after an interview with the subject, that the responses are consistent with suicidal 
ideation or attempt.  
9.6.2. 
Clinical Laboratory and Point of Care Tests 
For clinical laboratory data, descriptive statistics will be generated for all tests performed at 
screening and at each clinic visit. If a laboratory analysis is repeated, the last measurement 
performed prior to the clinic visit will be used in the summary statistics for that clinic visit. If an 
unscheduled clinical laboratory visit occurs prior to a scheduled visit that is missed due to 
dropout, then the unscheduled visit will be used in the summary statistics for the missed 
scheduled clinical visit. If an unscheduled clinical laboratory visit occurs between two scheduled 
clinical visits, then the data from the unscheduled visit only be presented in the listings and not in 
summary statistics. In addition, at each post-randomization clinic visit descriptive statistics for 
change from baseline will be generated. Laboratory values will be plotted as mean ± standard 
error over time. All laboratory measurements will be presented in the listings. 
Number and percentage of positive urine drug tests and pregnancy tests for screening visits and 
all treatment and follow-up visits will be tabulated. Results of all urine drug tests and pregnancy 
tests will be presented in the listings. The percentage of subjects with a positive urine drug test at 
any time post start of treatment will also be presented by test type and treatment group. 
9.6.3. 
Vital Signs, ECG, and Body Weight 
Vital signs will be presented as summary statistics and change from baseline. The percentage of 
ECG results considered abnormal and clinically significant will be provided. Body weight will 
be presented as summary statistics and change from screening. Vital signs, ECG results, and 
weight measurements for all visits will be presented in the listings. 


 
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9.6.4. 
CIWA-AR Scores 
The number and percentage of subjects who reported CIWA-AR scores ≥ 10 at any time after the 
start of dosing will be presented. 
9.6.5. 
ACQ-SF-R Scores 
Summary statistics for ACQ-SF-R raw scores prior to after each cue session will be presented. 
The number and percentage of subjects with a higher ACQ-SF-R score post each cue session will 
be provided by treatment group. 
9.7. 
Drug Exposure and Retention Analyses 
Drug exposure will be presented for each treatment group as the mean number of tablets taken by 
week and overall through AiCure during the entire treatment phase. The analysis will include the 
total number of tablets taken and the percent compliance. AiCure data will also be used for the 
number subjects receiving reminder intervention (phone calls, texts, or in person visits).  
Compliance will also be evaluated by determining the proportion of subjects who were 
prescribed ASP8062, reported taking ASP8062 (by AiCure assessment), and had a plasma 
sample with detectable ASP8062. Compliance by ASP8062 plasma levels will be reported as 
number and percentage of subjects with a level above the limit of detection at each time point. 
Descriptive statistics of plasma levels of ASP8062 and metabolites will also be provided. 
Samples with levels below of limit of quantitation will not be included in the summary statistics 
and the N will reflect the number with a detectable level at each timepoint. 
The participation rate is the percentage of subjects with complete drinking data. Dropouts by 
week with cumulative percentages will be provided by treatment arm. 
9.8. 
Blood Alcohol Content 
The number and percentage of subjects at any clinic visit that have a BAC > 0 will be tabulated. 
All BAC measurements will be presented in the listings. 
9.9. 
Exploratory and Ad Hoc Analyses 
9.9.1. 
Hyperkatifeia Scale  
There is interest in exploring the use of a new Hyperkatifeia Scale as a predictor of drug 
response and possibly as an outcome measure. Ad hoc analyses will be performed on this scale as 
a planned part of exploring the utility of this scale including subscales and individual items. Ad 
hoc analyses may include: 1) examining the association between cue outcomes and naturalistic 
outcomes; 2) conducting of moderator analyses; and 3) examining the treatment goal assessment 
and its relationship between outcomes. The data from this study could be used for combined 
analyses with results of other studies conducted in the future.  
9.9.2 
Supplemental Exploratory Analysis 
The exploratory analysis are defined as: Explore moderators of the treatment effect on primary 
and secondary outcomes. The exploratory endpoint will not be analyzed at the same time as the 
primary and secondary endpoints. 


 
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10. 
VALIDATION OF PROGRAMMING CODE 
All SAS codes used to generate tables and listings will be validated and reviewed before being 
finalized. The validation process will be used to determine that the numbers are produced by a 
statistically valid method and that the execution of the computations is correct. Qualified 
personnel who have not previously been involved in the production of the original programming 
codes will perform the validation procedures. Methods of validation include independent 
programming and comparison to data listings. Tables will be reviewed for accuracy, consistency 
with this plan, consistency within tables, and consistency with corresponding output. Once 
validation is complete, a quality control reviewer will perform a final review of the documents 
for accuracy and consistency. Upon completion of validation and quality review procedures, all 
documentation will be collected and filed in the study documentation files at Fast-Track. 


 
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11. 
REFERENCES 
Aubin HJ, Reimer J, Nutt DJ, Bladstrom A, Torup L, Francois C, Chick J. Clinical relevance of 
as-needed treatment with nalmefene in alcohol dependent patients. Eur Addict Res. 
2015;21:160–68. 
Buysse, D. J., Reynolds, C. F., 3rd, Monk, T. H., et al. The Pittsburgh Sleep Quality Index: a 
new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193-213. 
Caldeiro RM, Malte CA, Calsyn DA, Baer JS, Nichol P, Kivlahan DR, Saxon AJ. The 
association of persistent pain with out-patient addiction treatment outcomes and service 
utilization. Addiction. 2008;103:1996–2005. 
Carey KB. Reliability and validity of the time-line follow-back interview among psychiatric 
outpatients: a preliminary report. Psych Addic Behav. 1997;11, 26-33. 
Edlund MJ, Sullivan MD, Han X, Booth BM. Days with pain and substance use disorders: is 
there an association? Clin J Pain. 2013;29:689–695. 
Flannery BA, Volpicelli JR, Pettinati HM. Psychometric properties of the Penn Alcohol Craving 
Scale. Alcohol Clin Exp Res 1999;23:1289-95. 
Koob GF, Le Moal M. Drug abuse: hedonic homeostatic dysregulation. Science. 1997. 278:52–
58. 
Koob GF. Neurobiology of opioid addiction: opponent process, hyperkatifeia, and negative 
reinforcement. Biol Psychiatry. 2019;87:44–53. 
Koob GF. Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for 
Medications Development. Pharmacol Rev. 2021;73:163-201. 
Larson MJ, Paasche-Orlow M, Cheng DM, Lloyd-Travaglini C, Saitz R, Samet JH. Persistent 
pain is associated with substance use after detoxification: a prospective cohort analysis. 
Addiction. 2007;02:752–760. 
Lawton J, Simpson J. Predictors of alcohol use among people experiencing chronic pain. Psychol 
Health Med. 2009:14:487–501. 
Macefield RC, Metcalfe C, Lane JA, Donovan JL, Avery KNL, Blazeby JM, Down L, Neal DE, 
Hamdy FC, Vedhara K. Impact of prostate cance testing: evaluation of the emotional 
consequences of a negative biopsy result. Br J Cancer 2010;102:1335-1340. 
Mason BJ, Light JM, Williams LD, Drobes DJ. Proof-of-concept human laboratory study for 
protracted abstinence in alcohol dependence: Effects of gabapentin. Addict Biol. 2009;14:73-83. 
Mason BJ, Quello S, Goodell V, Shadan F. Gabapentin treatment for alcohol dependence. 
JAMA. 2014;174:70-77. 
McNair DM, Heuchert JWP. Profile of Mood States (POMS) Multi-Health Systems, Tonawanda, 
NY. 2005. 
Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number 
of events per variable in logistic regression analysis. 1996;49:1373-1379. 


 
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Pilkonis PA, Yu L, Colditz J, Dodds N, Johnston KL, Maihoefer C, Stover AM, Daley DC, 
McCarty D. Item banks for alcohol use from the Patient-Reported Outcomes Measurement 
Information System (PROMIS): use, consequences, and expectancies. Drug Alcohol Depend. 
2013;130:167-77. 
Roberts W, Harrison ELR, McKee S. Effects of varenicline on alcohol cue reactivity in heavy 
drinkers. Psychopharmacology (Berl). 2017;234:2737-2745. 
Sellers EM, Sullivan JT, Somer G, Sykora K. Characterization of DSM-III-R criteria for 
uncomplicated alcohol withdrawal: proposal for a diagnostic inventory and revised withdrawal 
scale. In Naranjo, C. A. and Sellers, E. M. (Eds.) Novel pharmacological interventions for 
alcoholism. New York (pp. 369-71). 1992. 
Singleton EG, Tiffany, ST, Henningfield JE. Development and validation of a new questionnaire 
to assess craving for alcohol. In: Harris LS (ed) Problems of Drug Dependence, 1994; 
Proceedings of the 56th Annual Scientific Meeting, The College on Problems of Drug 
Dependence, Inc. National Institute of Drug Abuse Research Monograph Series. Vol. 153. 
Rockville, MD 1995. p. 289. 
Sobell LC, Sobell MB, Leo GI, Cancilla A. Reliability of a timeline method: assessing normal 
drinkers' reports of recent drinking and a comparative evaluation across several populations. Br J 
Addict. 1988;83:393-402. 
Sobell LC, Brown J, Leo GI, Sobell MB. The reliability of the Alcohol Timeline Followback 
when administered by telephone and by computer. Drug Alcohol Depend 1996;42:49-54. 
Stuppaeck CH, Barnas C, Falk M, Guenther V, Hummer M, Oberbauer H, Pycha R, Whitworth 
AB, Fleischhacker WW. Assessment of the alcohol withdrawal syndrome--validity and 
reliability of the translated and modified Clinical Institute Withdrawal Assessment for Alcohol 
scale (CIWA-A). Addiction. 1994;89:1287-92. 
Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol 
withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-AR). 
Br J Addict. 1989;84:1353-7. 
Witkiewitz K, Maisto SA, Donovan DM. A comparison of methods for estimating change in 
drinking following alcohol treatment. Alcohol Clin Exp Res. 2010;34:2116–212. 
World Health Organization (WHO): International Guide for Monitoring Alcohol Consumption 
and Related Harm. Geneva, WHO, 2000. Available at: 
http://whqlibdoc.who.int/hq/2000/who_msd_msb_00.4.pdf. 
 
 


 
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12. 
TABLE, LISTING, AND FIGURE SHELLS 
12.1. 
Tables 
12.1.1. 
Subject Disposition, Participation, Compliance 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
42  
Table 1: Subject Disposition - All Randomized Subjects 
 
Notes: 1 p-value from Fisher’s exact test.  
2The following percentages are based upon number randomized 
3Completed is defined as attending all clinical visits through Week 7 making the subject available for all endpoint analyses 
4The following categories sum to the number of early withdrawals  
 
ASP8062 
Placebo 
Total 
 
 
n (%) 
n (%) 
n (%) 
p-value1 
 
 
 
 
 
Number of Subjects Consented 
 
 
xx 
 
Number of Subjects Screen Failed 
 
 
xx 
 
Number of Subjects Randomized2 
xx 
xx 
xx 
0.xxx 
Number of Subjects Randomized not Receiving Study Drug 
x (xx.x) 
x (xx.x) 
x (xx.x) 
0.xxx 
Number of mITT Subjects 
xx (xx.x) 
xx (xx.x) 
xxx (xx.x) 
0.xxx 
Number of Completed3 Subjects 
xx (xx.x) 
xx (xx.x) 
xxx (xx.x) 
0.xxx 
Number of Evaluable Subjects 
xx (xx.x) 
xx (xx.x) 
xxx (xx.x) 
0.xxx 
Number of Subject Completing Study & Drug 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
0.xxx 
Number of Subjects Discontinuing Study Drug, Remaining in Study 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
0.xxx 
Number of Subjects Withdrawn Early (did not provide any data at 
Week 7) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
0.xxx 
Reason for Early Withdrawal4 
 
 
 
 
    Subject withdrew consent 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
    Investigator withdrew subject 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
    Lost-to-followup 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   Adverse Event  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   Increased drinking 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   Psychiatric crisis 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   Died 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   Absent from the protocol due to confinement in a controlled 
environment 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   Determined after randomization to be ineligible 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 


 
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43  
Programmer Notes: The discontinuation reasons are as given on the CRF. Include only the reasons actually used for the subjects in the study. If a 
subject discontinued, but the specific reason is missing, include ‘Missing’ as a row in the table. Use the order of discontinuation reasons as 
presented on the CRF page. 
 
 


 
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Table 2: 
Exposure to Investigational Products Using AICure Data – mITT Subjects 
 
Number of Tablets Taken 
 
 
ASP8062 
N=XX 
Placebo 
N=XX 
 
 
N 
Mean (SD3) 
Med 
(Min-Max) 
N 
Mean (SD) 
Med 
(Min-Max) 
p-value1 
Week 1 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
0.xxx 
Week 2 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
0.xxx 
Week 3 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
0.xxx 
Week 4 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
0.xxx 
Week 5 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
0.xxx 
Week 6 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
0.xxx 
  Total Dose2 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
0.xxx 
1 p-value from t-test 
2 Dose is the total number of tablets taken, maximum prescribed is 42 tablets 
3 SD is standard deviation 
 
Table 3: 
Total Exposure to Investigational Products Using AICure Data – Evaluable Subjects 
Same as Table 2 only using evaluable subjects 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Table 4: 
Compliance to Investigational Products Using AICure Data – mITT Subjects 
Same analysis as Table 2 using compliance rather than dose. Compliance is the number of capsules taken/number of capsules 
prescribed. 
 
Table 5: 
Compliance to Investigational Products Using AICure Data – Evaluable Subjects 
Same analysis as Table 4 using evaluable subjects 
 
Table 6: 
AiCure  Interventions mITT Subjects 
 
ASP8062 
Placebo 
 
N 
# Receiving ≥ 1 
N 
# Receiving ≥ 1 
Interventions1 
xx 
xx 
xx 
xx 
1 Interventions includes texts, emails, and phone calls  
 
Table 7: 
 AiCure  Interventions  – Evaluable Subjects 
Same as Table 6 only using evaluable subjects 
 
 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
46  
Table 8: Summary of ASP8062 and Metabolite Plasma Levels – ASP8062 Arm Only (mITT Subjects) 
 
ASP8062 
 
N 
% > LLD1 
Mean (SD2) 
(Min-Max) 
    Week 4 
xx 
xx.x 
xx.x (xx.x) 
(xx.x-xx.x) 
    Week 7 
xx 
xx.x 
xx.x (xx.x) 
(xx.x-xx.x) 
 
AS3486189 
 
N 
% > LLD1 
Mean (SD2) 
(Min-Max) 
    Week 4 
xx 
xx.x 
xx.x (xx.x) 
(xx.x-xx.x) 
    Week 7 
xx 
xx.x 
xx.x (xx.x) 
(xx.x-xx.x) 
 
AS3486191 
 
N 
% > LLD1 
Mean (SD2) 
(Min-Max) 
    Week 4 
xx 
xx.x 
xx.x (xx.x) 
(xx.x-xx.x) 
    Week 7 
xx 
xx.x 
xx.x (xx.x) 
(xx.x-xx.x) 
 
AS3486192 
 
N 
% > LLD1 
Mean (SD2) 
(Min-Max) 
    Week 4 
xx 
xx.x 
xx.x (xx.x) 
(xx.x-xx.x) 
    Week 7 
xx 
xx.x 
xx.x (xx.x) 
(xx.x-xx.x) 
1 LLD is lowest level of detection2 SD is standard deviation 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Table 9: 
Summary of ASP8062 Plasma Levels – ASP8062 Arm Only (Evaluable Subjects) 
Same as Table 8 only using evaluable subjects. 
 
Table 10: 
AiCure Report of ASP8062 Versus ASP8062 Plasma Levels – mITT Subjects 
 
AiCure Report Indicates 
Drug Taken (pill count must = 
1, on the day before the blood 
sample was drawn) 
  
Timing 
Plasma level 
Indicates Drug 
Takena 
Yes, n (%) 
No, n (%) 
p-valueb 
kappac 
Week 4 
Yes 
 
 
 
 
 
No 
 
 
 
 
Week 7 
Yes 
 
 
 
 
 
No 
 
 
 
 
Overall 
Yes 
 
 
 
 
 
No 
 
 
 
 
 
a 
Blood level of  ≥xx ng/mL indicates drug taken 
b 
Chi-square test for independence 
c 
Kappa test for agreement 
Table 11:  
AiCure Report of ASP8062 Versus ASP8062 Plasma Levels – Evaluable Subjects 
Repeat of Table 10 using evaluable subjects 
 
 
 
 
Table 12: 
 Exit Interview – mITT Subjects 
 
 ASP8062 
Placebo 
         Total 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Question 
(N=xx) 
(N=xx) 
       (N=xxx) 
p-value1 
Did you think you were receiving 
the study drug or the placebo?  
 
 
 
0.xxx 
  Placebo 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Study Drug 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Don’t know; No idea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Refuse to answer 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
What is your desire to please 
people? 
 
 
 
0.xxx 
  More than average 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Average 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Less than average  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Refuse to answer 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Take the study drug again, for 
more than 6 weeks?   
  Yes  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
0.xxx 
  No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 Refuse to answer 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Did you ever miss a dose of 
medication to avoid these effects? 
 
 
 
 
  Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
0.xxx 
  No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Refuse to answer 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Did you use any other services 
during the study to help you 
reduce drinking? 
  Yes  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
0.xxx 
  No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 Refuse to answer 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
1 p-value from chi-squared test (c) unless one of the cells expected is less than 5 then Fisher’s exact test is used (f). Refuse to answer is not included in 
statistical test. 
 
 
Table 13: 
 Exit Interview – Evaluable Subjects 
Same as Table 12 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Table 14: 
 Dropouts by Treatment Group and Week – mITT Subjects 
 
 ASP8062 
N=XX 
Placebo 
N=XX 
Total 
N=XX 
 
Study 
Week2 
n 
Cumulative 
n (%) 
n 
Cumulative 
n (%) 
n 
Cumulative 
 n (%) 
p-value1 
Week 1 
xx 
xx (xx.x) 
xx 
xx  (xx.x) 
xx 
xx (xx.x) 
0.xxx 
Week 2 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
0.xxx 
Week 3 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
0.xxx 
Week 4 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
0.xxx 
Week 5 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
0.xxx 
Week 6 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
0.xxx 
Week 6 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
xx 
xx (xx.x) 
0.xxx 
1 Fisher’s exact test  
2Subjects are considered dropouts when they stop providing TLFB and other data. Subjects that discontinue study drug but provide data are not 
considered dropouts. 
 
Table 15: 
Number and Percent of Subjects Using Brief Drinking Questions after Discontinuing TLFB – mITT Subjects 
 
 ASP8062 
Placebo 
Total 
 
Study Week 
n (%)  
n (%) 
n (%) 
p-value1 
Week 3 
xx (xx.x) 
xx 
 xx.x 
0.xxx 
Week 4 
xx 
xx 
 xx.x 
0.xxx 
Week 5 
xx 
xx 
 xx.x 
0.xxx 
Week 6 
xx 
xx 
 xx.x 
0.xxx 
Week 6 
xx 
xx 
 xx.x 
0.xxx 
Overall 
xx 
xx 
 xx.x 
0.xxx 
1Fisher’s exact test is used because frequencies are expected to be low 
Note only rows with values above 0 will be presented 


 
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12.1.2. 
Demographic and Baseline Characteristics 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Table 16: Demographic Characteristics - mITT Subjects 
Characteristic 
 ASP8062 
Placebo 
Total 
p-value1 
Age (years) 
 
 
 
0.xxx 
  N 
xx 
xx 
xx 
 
  Mean 
xx.x 
xx.x 
xx.x 
 
  SD2 
xxx.xx 
xxx.xx 
xxx.xx 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
Gender 
 
 
 
0.xxx 
  N 
 
 
 
 
  Male 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Female 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Race 
 
 
 
0.xxx 
  N 
xx 
xx 
xx 
 
  White 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  African-American or Black  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Asian 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Native Hawaiian or Other Pacific Islander 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  American Indian or Alaskan Native 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Ethnicity 
 
 
 
0.xxx 
  N 
xx 
xx 
xx 
 
  Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Not Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
1c = chi-squared test, f=Fisher’s exact test, w=Wilcoxon signed rank test 
2 SD is standard deviation 
 
 
Table 17: 
Demographic Characteristics – Evaluable Subjects 
Same as Table 16 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Table 18: 
Screening Cue Reactivity – mITT Subjects 
 
 
 
ASP8062 
N=xx 
 
Placebo 
N=xx 
Total 
N=xx 
p-value1 
Cue 
Question 
Statistic 
 
 
 
 
Water 
Craving 
Strength 
 
 
 
 
0.xxx 
 
 
  Mean (SD2) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 
Drinking makes 
things perfect 
 
 
 
 
0.xxx 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 
Drink now 
 
 
 
 
0.xxx 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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ASP8062 
N=xx 
 
Placebo 
N=xx 
Total 
N=xx 
p-value1 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 
Turn down drink  
 
 
 
0.xxx 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 
Average 
 
 
 
 
0.xxx 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
Alcohol  
Craving 
Strength 
 
 
 
 
0.xxx 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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ASP8062 
N=xx 
 
Placebo 
N=xx 
Total 
N=xx 
p-value1 
 
Drinking makes 
things perfect 
 
 
 
 
0.xxx 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 
Drink now 
 
 
 
 
0.xxx 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 
Turn down drink  
 
 
 
0.xxx 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 
Average 
 
 
 
 
0.xxx 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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ASP8062 
N=xx 
 
Placebo 
N=xx 
Total 
N=xx 
p-value1 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
Alcohol - 
Water 
Craving 
Strength 
 
 
 
 
0.xxx 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 
Drinking makes 
things perfect 
 
 
 
 
0.xxx 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 
Drink now 
 
 
 
 
0.xxx 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 
Turn down drink  
 
 
 
0.xxx 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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ASP8062 
N=xx 
 
Placebo 
N=xx 
Total 
N=xx 
p-value1 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 
Average 
 
 
 
 
0.xxx 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
  Median 
xx 
xx 
xx 
 
 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
1 t-test is used to examine balance across treatment groups 
2 SD is standard deviation 
 
 
 
Table 19: 
Screening Cue Reactivity – Evaluable Subjects 
Same as Table 18 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Table 20: 
Psychiatric Baseline Characteristics – mITT Subjects 
 
 ASP8062 
Placebo 
Total 
Characteristic 
(N=xx) 
(N=xx) 
(N=xxx) 
DSM-5 Disorders 
 
 
 
  Depression 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Suicidality 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Manic 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Hypomanic 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Bipolar 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Panic 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Agoraphobia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Social Phobia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Obsessive Compulsive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Posttraumatic Stress 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Substance Abuse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Psychotic 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Mood 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Anorexia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Bulemia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Binge-eating 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Generalized Anxiety 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Medical Organic 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Antisocial Personality 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Table 21:  
Medical History – mITT Subjects 
Medical History SOC and Preferred Term 
ASP8062 
(N=xx) 
Placebo 
(N=xx) 
Total 
(N=xx) 
SOC 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Preferred term name 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 


 
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Table 22: 
Baseline POMS – mITT Subjects 
Characteristic 
ASP8062 
(N=xx) 
Placebo 
(N=xx) 
Total 
(N=xx) 
p-value1 
Tension-Anxiety 
 
 
 
0.xxx 
  N 
xx 
xx 
xx 
 
  Mean 
xx.x 
xx.x 
xx.x 
 
  SD2 
xxx.xx 
xxx.xx 
xxx.xx 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 Scale Min-Max 
 
 
(xx-xx) 
 
Depression-Dejection 
 
 
 
0.xxx 
  N 
xx 
xx 
xx 
 
  Mean 
xx.x 
xx.x 
xx.x 
 
  SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 Scale Min-Max 
 
 
(xx-xx) 
 
Anger-Hostility 
 
 
 
0.xxx 
  N 
xx 
xx 
xx 
 
  Mean 
xx.x 
xx.x 
xx.x 
 
  SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 Scale Min-Max 
 
 
(xx-xx) 
 
Fatigue-Inertia 
 
 
 
0.xxx 
  N 
xx 
xx 
xx 
 
  Mean 
xx.x 
xx.x 
xx.x 
 
  SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 Scale Min-Max 
 
 
(xx-xx) 
 
Confusion-Bewilderment 
 
 
 
0.xxx 
  N 
xx 
xx 
xx 
 
  Mean 
xx.x 
xx.x 
xx.x 
 
  SD 
xxx.xx 
xxx.xx 
xxx.xx 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Characteristic 
ASP8062 
(N=xx) 
Placebo 
(N=xx) 
Total 
(N=xx) 
p-value1 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 Scale Min-Max 
 
 
(xx-xx) 
 
Vigor-Activity 
 
 
 
0.xxx 
  N 
xx 
xx 
xx 
 
  Mean 
xx.x 
xx.x 
xx.x 
 
  SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 Scale Min-Max 
 
 
(xx-xx) 
 
Total Mood Disturbance 
 
 
 
0.xxx 
  N 
xx 
xx 
xx 
 
  Mean 
xx.x 
xx.x 
xx.x 
 
  SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 Scale Min-Max 
 
 
(xx-xx) 
 
1 t-test 
2SD is standard deviation 
 
Table 23: 
Baseline POMS – Evaluable Subjects 
Same as Table 22 
 
 
Table 24: 
Baseline PSQI – mITT Subjects 
Characteristic 
ASP8062 
Placebo 
Total 
p-value1 
Overall Sleep Experience 
 
 
 
0.xxx 
  N 
xx 
xx 
xx 
 
  Mean 
xx.x 
xx.x 
xx.x 
 
  SD2 
xxx.xx 
xxx.xx 
xxx.xx 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Characteristic 
ASP8062 
Placebo 
Total 
p-value1 
 Scale Min-Max 
 
 
(xx-xx) 
 
1 t-test 
2 SD is standard deviation 
 
 
Table 25: 
 Baseline PSQI – Evaluable Subjects 
Same as Table 24 


 
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Table 26: 
Baseline Drinking-related Behavior and Characteristics – mITT Subjects 
 
ASP8062 
Placebo 
Total 
 
Characteristic 
(N=xx) 
(N=xx) 
(N=xx) 
p-value1 
Drinking Goal (n, %) 
 
 
 
 
   Stop Drinking 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   Reduce but not stop 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Goal of no heavy drinking days (n, %) 
 
 
 
 
   Yes 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   No 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
# Drinks/Week Goal in Subjects that Want to Reduce Drinking 
 
 
 
   N 
xx 
xx 
xx 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD2 
xxx.xx 
xxx.xx 
xxx.xx 
 
   Median 
xx 
xx 
xx 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
Motivation to achieve goal 
 
 
 
   N 
xx 
xx 
xx 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
   Median 
xx 
xx 
xx 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
Confidence in achieving goal 
 
 
 
   N 
xx 
xx 
xx 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
   Median 
xx 
xx 
xx 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
AUD Symptom Severity (n, %) 
 
 
 
0.xxx 
    Moderate (4 or 5 symptoms) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
    Severe (6 or more symptoms) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
AUD Number of Symptoms (n, %) 
 
 
 
 
  4 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  5   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  6 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  7 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  8 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  9 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 10 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
62  
 
ASP8062 
Placebo 
Total 
 
Characteristic 
(N=xx) 
(N=xx) 
(N=xx) 
p-value1 
 11 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
AUD Number of Symptoms (continuous) 
 
 
 
0.xxx 
  Mean 
xx.x 
xx.x 
xx.x 
 
  SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
  Median 
xx 
xx 
xx 
 
Note: Percentages are based on the number of non-missing values in each variable.  
1  t-test  
2SD is standard deviation 
 
Table 27: 
 Baseline Drinking-related Behavior and Characteristics – Evaluable Subjects 
Same as Table 26 
 
 
 
 
 
 
 
 
Table 28: 
Baseline Drinking by TLFB – mITT Subjects 
 
ASP8062 
Placebo 
Total 
 
Parameter 
(N=xx) 
(N=xx) 
(N=xxx) 
p-value1 
  Drinks/Week (Pre-screening Days -1 to -28) 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD2 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
  Drinks/Week (7 Days Prior to Randomization) 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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ASP8062 
Placebo 
Total 
 
Parameter 
(N=xx) 
(N=xx) 
(N=xxx) 
p-value1 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
  Drinks/Week (Percent Change Pre-screening Days 
-1 to -28 to 7 Days Prior to Randomization) 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
  Drinks/Drinking Day (Pre-screening Days -1 to -
28) 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
  Drinks/Drinking Day (7 Days Prior to 
Randomization) 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
  Drinks/Drinking Day (Percent Change Pre-
screening Days -1 to -28 to 7 Days Prior to 
Randomization) 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 Percentage of Heavy Drinking Days  
  (Pre-screening Days -1 to -28) 
 
 
 
0.xxx 
   Mean 
xx.x% 
xx.x% 
xx.x% 
 
   SD 
xx.x% 
xx.x% 
xx.x% 
 
   Median 
xx.x% 
xx.x% 
xx.x% 
 
   Min-Max 
(xx%-xx%) 
(xx%-xx%) 
(xx%-xx%) 
 
 Percentage of Very Heavy Drinking Days  
  (Pre-screening Days -1 to -28) 
 
 
 
0.xxx 
   Mean 
xx.x% 
xx.x% 
xx.x% 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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ASP8062 
Placebo 
Total 
 
Parameter 
(N=xx) 
(N=xx) 
(N=xxx) 
p-value1 
   SD 
xx.x% 
xx.x% 
xx.x% 
 
   Median 
xx.x% 
xx.x% 
xx.x% 
 
   Min-Max 
(xx%-xx%) 
(xx%-xx%) 
(xx%-xx%) 
 
 Percentage Days Abstinent  
  (Pre-screening Days -1 to -28) 
 
 
 
0.xxx 
   Mean 
xx.x% 
xx.x% 
xx.x% 
 
   SD 
xx.x% 
xx.x% 
xx.x% 
 
   Median 
xx.x% 
xx.x% 
xx.x% 
 
   Min-Max 
(xx%-xx%) 
(xx%-xx%) 
(xx%-xx%) 
 
WHO Risk Level 
 
 
 
0.xxx 
  High Risk 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 Very High Risk 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Note: Percentages are based on the number of non-missing values in each variable.  
1Chi-square test for categorical variables and t-test for continuous variables 
2 SD is standard deviation 
 
Table 29: 
Baseline Drinking by TLFB – Evaluable Subjects 
Same as Table 28 
 


 
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Table 30: 
Baseline Alcohol-Related Craving, Consequences, Withdrawal and Hyperkatifeia – mITT Subjects 
 
ASP8062 
Placebo 
Total 
 
Parameter 
(N=xx) 
(N=xx) 
(N=xxx) 
p-value1 
Pre-cue ACQ-SF-R2 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD3 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
   Scale Min-Max 
 
 
(xx.x – xx.x) 
 
Post-cue ACQ-SF-R 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
Pre-Post ACQ-SF-R 
 
 
 
 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 PROMIS4 Alcohol Negative 
Consequences (T-scores) 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
 PACS5 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
   Scale Min-Max 
 
 
(xx.x – xx.x) 
 
 CIWA-AR6 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
   Scale Min-Max 
 
 
(xx.x – xx.x) 
 


 
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ASP8062 
Placebo 
Total 
 
Parameter 
(N=xx) 
(N=xx) 
(N=xxx) 
p-value1 
Withdrawal Symptoms (CIWA ≥ 10) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
0.xxx 
Hyperkatifeia 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
   Scale Min-Max 
 
 
(xx.x – xx.x) 
 
Stress Anxiety 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
   Scale Min-Max 
 
 
(xx.x – xx.x) 
 
Depression 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
   Scale Min-Max 
 
 
(xx.x – xx.x) 
 
Irritable 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
   Scale Min-Max 
 
 
(xx.x – xx.x) 
 
Pain 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
   Scale Min-Max 
 
 
(xx.x – xx.x) 
 
1 t-test for continuous variables and chi-square test for categorical 
2ACQ-SF-R is Alcohol Craving Questionnaire – Short Form – Revised  
3 SD is standard deviation  
4 PROMIS is short form of Patient-reported Outcomes Information System 
 5 PACS is Penn Alcohol Craving Scale 6 CIWA-AR is Clinical Institute Withdrawal Assessment for Alcohol-revised 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Table 31: 
Baseline Alcohol-Related Craving, Consequences, Withdrawal and Hyperkatifeia – Evaluable Subjects 
Same as Table 30 
 
 Table 32: 
Baseline Other Substance Use – mITT Subjects 
 
ASP8062 
Placebo 
Total 
 
Parameter 
(N=xx) 
(N=xx) 
(N=xxx) 
p-value1 
Smoker (n, %) 
xx (xx) 
xx (xx) 
xx (xx) 
0.xxx 
Days Smoked in the Past Week 
 
 
 
 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD2 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   (Min-Max) 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
Average Cigarettes Smoked Per Week (among 
Smokers) 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
Any Other Nicotine Product Use (doesn’t include 
cigarettes) (n, %) 
xx (xx) 
xx (xx) 
xx (xx) 
0.xxx 
Days Used Other Nicotine Products Per Week 
 
 
 
0.xxx 
   Mean 
xx.x 
xx.x 
xx.x 
 
   SD 
xx.x 
xx.x 
xx.x 
 
   Median 
xx.x 
xx.x 
xx.x 
 
   Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
 
Any Nicotine Use (cigarettes + other) (n, %) 
xx (xx) 
xx (xx) 
xx (xx) 
0.xxx 
THC 
 
 
 
0.xxx 
  Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
  Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Note: Percentages are based on the number of non-missing values in each variable.  
1t-test for continuous variables and chi-square test for categorical 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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2 SD is standard Deviation 
 
Table 33: 
Baseline Other Substance Use – Evaluable Subjects 
Same as Table 32 
 


 
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12.1.3. 
Primary Efficacy Endpoint


 
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Table 34: 
Week 3 Strength of Craving Scores – mITT Subjects 
 
 
ASP8062 
N=xx 
Placebo 
N=xx 
Total 
N=xx 
Cue 
Statistic 
 
 
 
Water 
 
 
 
 
 
  Mean (SD1) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
Alcohol  
 
 
 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
Alcohol  - Water 
 
 
 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
1 SD is standard deviation 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Table 35: 
Week 3 Strength of Craving Scores – Evaluable Subjects 
Same as Table 34 
 
Table 36: 
ANCOVA Strength of Craving – mITT Subjects  
Type III Wald Tests 
Parameter 
Num DF1 
Den DF2 
F Value 
 
p-value 
Arm 
1 
xx 
xxx.xx 
0.xxx 
Site 
xx 
xx 
xxx.xx 
0.xxx 
Baseline Cue3 
1 
xx 
xxx.xx 
0.xxx 
1Numerator degrees of freedom; 2 Demonimator degrees of freedom 
3 Baseline Cue is the baseline equivalent of the outcome obtained after the presentation of the first alcohol cue at baseline 
 
Least Squares Means  
 
 
 
95% CI 
 
 
 
Arm 
Estimate SE1 
Lower CI 
Upper CI Difference SE 
p-value2 
Cohen’s d 
ASP8062 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 0.xxx 
xx.xxx 
Placebo 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
1 SE is standard error; 2 Wald test;  
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Table 37: 
ANCOVA Strength of Craving – Evaluable Subjects 
Follow the same analysis as Table 36 
 
 
 
 


 
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12.1.4. 
Confirmatory Secondary Efficacy Endpoints


 
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Table 38:  
ANCOVA Strength of Craving (Difference Alcohol-Water) – mITT Subjects 
Type III Wald Test 
Parameter 
Num DF1 
Den DF2 
F Value 
p-value 
Arm 
1 
xx 
xxx.xx 
0.xxx 
Site 
xx 
xx 
xxx.xx 
0.xxx 
Baseline Cue3 
1 
xx 
xxx.xx 
0.xxx 
1Numerator degrees of freedom; 2 Demonimator degrees of freedom 
3 Baseline Cue is the baseline equivalent of the outcome obtained after the presentation of the first alcohol cue at baseline 
 
 
Least Squares Means  
 
 
 
95% CI 
 
 
 
Arm 
Estimate SE1 
Lower CI 
Upper CI Difference SE 
p-value2 
Cohen’s d 
ASP8062 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 0.xxx 
xx.xxx 
Placebo 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
1 SE is standard error; 2 Wald test;  
 
Table 39: 
ANCOVA Strength of Craving (Difference Alcohol-Water)  – Evaluable Subjects 
Same as Table 38 
 


 
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Table 40: 
Drinking Makes Things Perfect Scores – mITT Subjects 
 
 
ASP8062 
N=xx 
Placebo 
N=xx 
Total 
N=xx 
Cue 
Statistic 
 
 
 
Water 
 
 
 
 
 
  Mean (SD1) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
Alcohol  
 
 
 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
Alcohol- Water 
 
 
 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
1 SD is standard deviation 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Table 41: 
Drinking Makes Things Perfect Scores – Evaluable Subjects 
Same as Table 40 
 
 
Table 42: 
ANCOVA Drinking Makes Things Perfect  – mITT Subjects 
Type III Wald Test 
Parameter 
Num DF1 
Den DF2 
F Value 
p-value 
Arm 
1 
xx 
xxx.xx 
0.xxx 
Site 
2 
xx 
xxx.xx 
0.xxx 
Baseline Cue3 
1 
xx 
xxx.xx 
0.xxx 
1Numerator degrees of freedom; 2 Demonimator degrees of freedom 
3 Baseline Cue is the baseline equivalent of the outcome obtained after the presentation of the first alcohol cue at baseline  
 
Least Squares Means  
 
 
 
95% CI 
 
 
 
Arm 
Estimate SE1 
Lower CI 
Upper CI Difference SE 
p-value2 
Cohen’s d 
ASP8062 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 0.xxx 
xx.xxx 
Placebo 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
1 SE is standard error; 2 Wald test;  
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Table 43: 
ANCOVA Drinking Makes Things Perfect  – Evaluable Subjects 
Same analysis as Table 42 
 
Table 44: 
ANCOVA Drinking Makes Things Perfect (Difference Alcohol-Water) – mITT Subjects 
Type III Wald Test 
Parameter 
Num DF1 
Den DF2 
F Value 
p-value 
Arm 
2 
xx 
xxx.xx 
0.xxx 
Site 
2 
xx 
xxx.xx 
0.xxx 
Baseline Cue3 
1 
xx 
xxx.xx 
0.xxx 
1Numerator degrees of freedom; 2 Demonimator degrees of freedom 
3 Baseline Cue is the baseline equivalent of the outcome obtained after the presentation of the first alcohol cue at baseline  
 
Least Squares Means  
 
 
 
95% CI 
 
 
 
Arm 
Estimate SE1 
Lower CI 
Upper CI Difference SE 
p-value2 
Cohen’s d 
ASP8062 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 0.xxx 
xx.xxx 
Placebo 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
1 SE is standard error; 2 Wald test;  
 
 


 
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Table 45: 
ANCOVA Drinking Makes Things Perfect (Difference Alcohol-Water) – Evaluable Subjects 
Same analysis as Table 44 
 
 
 
Table 46: 
Drink Now Scores– mITT Subjects 
 
 
ASP8062 
N=xx 
Placebo 
N=xx 
Total 
N=xx 
Cue 
Statistic 
 
 
 
Water 
 
 
 
 
 
  Mean (SD1) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
Alcohol 
 
 
 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
Alcohol - Water 
 
 
 
 
 
  Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 


 
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ASP8062 
N=xx 
Placebo 
N=xx 
Total 
N=xx 
 
  Median 
xx 
xx 
xx 
 
  Min-Max 
(xx-xx) 
(xx-xx) 
(xx-xx) 
1 SD is standard deviation 
 
Table 47: 
Drink Now Scores – Evaluable Subjects 
Same as Table 46 
 
 
Table 48: 
ANCOVA Drink Now  – mITT Subjects 
Type III Wald Test 
Parameter 
Num DF1 
Den DF2 
F Value 
p-value 
Arm 
1 
xx 
xxx.xx 
0.xxx 
Site 
xx 
xx 
xxx.xx 
0.xxx 
Baseline Cue3 
1 
xx 
xxx.xx 
0.xxx 
1Numerator degrees of freedom; 2 Demonimator degrees of freedom 
3 Baseline Cue is the baseline equivalent of the outcome obtained after the presentation of the first alcohol cue at baseline  
 
 


 
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80  
Least Squares Means  
 
 
 
95% CI 
 
 
 
Arm 
Estimate SE1 
Lower CI 
Upper CI Difference SE 
p-value2 
Cohen’s d 
ASP8062 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 0.xxx 
xx.xxx 
Placebo 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
1 SE is standard error; 2 Wald test;  
 
 
Table 49: 
ANCOVA Drink Now  – Evaluable Subjects 
Same analysis as Table 48 
Table 50: 
ANCOVA Drink Now (Difference Alcohol-Water) – mITT Subjects 
Same analysis as Table 44 with difference as the dependent variable 
Table 51: 
ANCOVA Drink Now (Difference Alcohol-Water) – Evaluable Subjects 
Same analysis as Table 50 
Table 52: 
Turn Down Drink Scores – mITT Subjects 
Same analysis as Table 46 
Table 53: 
Turn Down Drink Scores – Evaluable Subjects 
Same analysis as Table 52 
Table 54: 
ANCOVA Turn Down Drink – mITT Subjects 
Same analysis as Table 48 


 
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Table 55: 
ANCOVA Turn Down Drink  – Evaluable Subjects 
Same analysis as Table 54 
Table 56: 
ANCOVA Turn Down Drink (Difference Alcohol-Water) – mITT Subjects 
Same analysis as Table 44  
Table 57: 
ANCOVA Turn Down Drink (Difference Alcohol-Water) – Evaluable Subjects 
Same analysis as Table 56 
Table 58: 
Average of Cue Scores – mITT Subjects 
Same analysis as Table 46 
Table 59: 
Average of Cue Scores – Evaluable Subjects 
Same as Table 58 
Table 60:  
ANCOVA Average of Cue Scores – mITT Subjects 
Same analysis as Table 48 
 Table 61: 
ANCOVA Average of Cue Scores – Evaluable Subjects 
 Same analysis as Table 60 
Table 62: 
ANCOVA Average of Cue Scores (Difference Alcohol-Water) – mITT Subjects 
Same analysis as Table 44  
Table 63: 
ANCOVA Average of Cue Scores (Difference Alcohol-Water) – Evaluable Subjects 
Same analysis as Table 62 
Table 64: 
Beverage Liking Scores – mITT Subjects 
Same analysis as Table 46 
Table 65: 
Beverage Liking Scores – Evaluable Subjects 
Same analysis as Table 64 
 


 
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12.1.5. 
Secondary Efficacy Endpoints 
 


 
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83  
Table 66: 
Percentage of Subjects No Heavy Drinking Days Weeks 3-6 – mITT Subjects 
 
ASP8062 
Placebo 
Total 
 
(N=xx) 
(N=xx) 
(N=xxx) 
No Heavy Drinking Days 
 
 
 
  Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Table 67: 
Percentage of Subjects with No Heavy Drinking Days Weeks 3-6 – Full Model Logistic Regression (mITT) 
 
 
 
 
 
 
 
 
 
95% CI3 
Parameter 
  
DF1 Estimate 
Standard  
Error 
Wald  
Chi-Square 
Pr > Chi- 
Square 
Cohen’s h 
OR2 
Upper 
Lower 
Intercept 
  
1 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
 
 
 
Treatment 
Overall 
X 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
 
 
 
Treatment4 
ASP8062 
X 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
0.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
Site 
Overall 
X 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
 
 
 
Site5 
1 
X 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
xx.xxx 
xx.xxx 
xx.xxx 
Site 
2 
X 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
xx.xxx 
xx.xxx 
xx.xxx 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
84  
 
 
 
 
 
 
 
 
 
95% CI3 
Parameter 
  
DF1 Estimate 
Standard  
Error 
Wald  
Chi-Square 
Pr > Chi- 
Square 
Cohen’s h 
OR2 
Upper 
Lower 
Cov 
 
X 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
xx.xxx 
xx.xxx 
xx.xxx 
1  DF is degrees of freedom; 2 OR is odds ratio; 3 CI is confidence interval;  4 Comparison to placebo; 
5 Site 3 is reference for the OR 
Programming note: COV is baseline equivalent of dependent variable and any other covariate(s) which have not been specified at the time of writing of SAP 
 
Table 68: 
Percentage of Subjects Abstinent from Alcohol Weeks 3-6 – mITT Subjects 
Presented in same manner as Table 66 
 
Table 69: 
Percentage of Subjects Abstinent from Alcohol Weeks 3-6 – Full Model Logistic Regression (mITT) 
Prented in same manner as Table 67 programming note: baseline PDA is a covariate for PSA outcome 
 
 
 
 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
85  
Table 70:  
WHO 1-Level Decrease in Alcohol Consumption (mITT) – Weeks 3-6 
 
 
ASP8062 
Placebo 
Total 
 
(N=xx) 
(N=xx) 
(N=xxx) 
WHO 1-Level Decrease 
 
 
 
  Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Table 71: 
WHO 1-Level Decrease in Alcohol Consumption (mITT) – Full Model, Logistic Regression, Weeks 2-5 
 
 
 
 
 
 
 
 
 
95% CI3 
Parameter 
  
DF1 Estimate 
Standard  
Error 
Wald  
Chi-Square 
Pr > Chi- 
Square 
Cohen’s h 
OR2 
Upper  
Lower 
Intercept 
  
1 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
 
 
 
Treatment 
Overall 
X 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
 
 
 
Treatment4 
ASP8062 
X 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
0.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
Site 
Overall 
X 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
 
 
 
Site5 
1 
X 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
xx.xxx 
xx.xxx 
xx.xxx 
Site 
2 
X 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
xx.xxx 
xx.xxx 
xx.xxx 
Cov 
 
X 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
xx.xxx 
xx.xxx 
xx.xxx 
 


 
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86  
1  DF is degrees of freedom; 2 OR is odds ratio; 3 CI is confidence interval;  4 Comparison to placebo; 
5 Site 3 is reference for the OR 
Programming note: COV is baseline equivalent of dependent variable and any other covariate(s) which have not been specified at the time of writing of SAP 
 
 
 
Table 72: 
WHO 2-Level Decrease in Alcohol Consumption (mITT) – Weeks 3-6 
Same as Table 70 
Table 73: 
WHO 2-Level Decrease in Alcohol Consumption (mITT) – Full Model, Logistic Regression, Weeks 3-6 
Same as Table 71  
 
 
 
Table 74: 
Percentage of Days Abstinent per Week (mITT) – Weeks 3-6 
 
ASP8062 
 
Placbo 
Study 
Week 
N 
Mean (SD1) 
Median 
(Min-Max) 
N 
Mean (SD) 
Median 
(Min-Max) 
3 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
4 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
5 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
6 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
Overall 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
1 SD is standard deviation 
 
 
 


 
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87  
Table 75: 
Percentage of Days Abstinent per Week (mITT) -- Full Model, Mixed Effects, Weeks 3-6 
Type III Wald Tests 
Parameter 
Num DF1 
Den DF2 
F Value 
 
p-value 
Arm 
1 
xxx 
xxx.xx 
0.xxx 
Week 
3 
xxx 
xxx.xx 
0.xxx 
Site 
xx 
xxx 
xxx.xx 
0.xxx 
Cov 
x 
xxx 
xxx.xx 
0.xxx 
Arm*Week 
5 
xxx 
xxx.xx 
0.xxx 
1 Numerator degrees of freedom; 2 Denominator degrees of freedom 
 
 
 
Programming note: Cov is the baseline equivalent of the dependent variable and any additional covariates included in 
the model. 
Least Squares Means 
 
 
 
 
95% CI2 
 
 
Model 
Arm 
Week 
Estimate 
SE1 
Lower CI 
Upper CI 
Difference 
SE 
p-value 
Cohen’s d 
ASP8062 
3 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 
0.xxx 
xx.xxx 
Placebo 
3 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
ASP8062 
4 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 
0.xxx 
xx.xxx 
Placebo 
4 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
ASP8062 
5 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 
0.xxx 
xx.xxx 
Placebo 
5 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
ASP8062 
6 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 
0.xxx 
xx.xxx 
Placebo 
6 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
ASP8062 
Overall  
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 
0.xxx 
xx.xxx 
Placebo 
Overall 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
88  
1 SE is standard error; 2 CI is confidence interval 
Programming note:If a transformation of the dependent variable is used add 2 columns: p-value and Cohen’s d for the transformed model. 
 
Table 45 is the template for Tables 76, 78, 80, 82, 84, and 86. Table 75 is the template for Tables 77, 79, 81, 83, 85, and 87. 
Table 76: 
Percentage of Heavy Drinking Days per Week (mITT) – Weeks 3-6 
Table 77: 
Percentage of Heavy Drinking Days per Week (mITT) – Full Model, Mixed Effects, Weeks 3-6 
Table 78: 
Percentage of Very Heavy Drinking Days per Week (mITT) – Weeks 3-6 
 
Table 79: 
Percentage of Very Heavy Drinking Days per Week (mITT) – Full Model, Mixed Effects, Weeks 3-6 
Table 80: 
Drinks per Week (mITT) – Weeks 3-6 
 
Table 81: 
Drinks per Week (mITT) – Full Model, Mixed Effects, Weeks 3-6 
Table 82: 
Drinks per Drinking Day (mITT) – Weeks 3-6 
 
Table 83: 
Drinks per Drinking Day (mITT) – Full Model, Mixed Effects, Weeks 3-6 
Table 84: 
Mean Cigarettes Smoked Among Smokers (mITT) – Weeks 3-6 
 
Table 85: 
Mean Cigarettes Smoked Among Smokers (mITT) – Full Model, Mixed Effects, Weeks 3-6 
Table 86: 
PACS (mITT) – Weeks 3-6 
 
Table 87: 
PACS (mITT) – Full Model, Mixed Effects, Weeks 3-6 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
89  
 
 
 
 
Table 88: 
Percentage of Subjects Abstinent from Nicotine Use1 Weeks 3-6 – Among Subjects that Used Nicotine Products 
at Baseline 
 
ASP8062 
Placebo 
Total 
 
(N=xx) 
(N=xx) 
(N=xxx) 
No Nicotine Use 
 
 
 
  Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
1 Nicotine use includes cigarettes or other nicotine products 
 
Table 89: 
Percentage of Subjects Abstinent from Nicotine Use1 Weeks 3-6 – Full Model Logistic Regression (Among 
Nicotine Users at Baseline) 
 
 
 
 
 
 
 
 
 
95% CI4 
Parameter 
  
DF2 Estimate 
Standard  
Error 
Wald  
Chi-Square 
Pr > Chi- 
Square 
Cohen’s h 
OR3 
Upper CI 
Lower CI 
Intercept 
  
1 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
 
 
 
Treatment 
Overall 
x 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
90  
 
 
 
 
 
 
 
 
 
95% CI4 
Parameter 
  
DF2 Estimate 
Standard  
Error 
Wald  
Chi-Square 
Pr > Chi- 
Square 
Cohen’s h 
OR3 
Upper CI 
Lower CI 
Treatment5 
ASP8062 x 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
0.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
Site 
Overall 
x 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
 
 
 
Site6 
1 
x 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
xx.xxx 
xx.xxx 
xx.xxx 
Site 
2 
x 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
xx.xxx 
xx.xxx 
xx.xxx 
Cov 
 
x 
xx.xxx 
xx.xxx 
xx.xxx 
0.xxx 
 
xx.xxx 
xx.xxx 
xx.xxx 
1  Nicotine use includes either cigarettes or other nicotine products; 2 DF is degrees of freedom; 3 OR is odds ratio; 4 CI is confidence 
interval;  5 Comparison to placebo for each active treatment;6 Site 3 is reference for the OR 
Programming note: COV is baseline equivalent of dependent variable and any other covariate(s) which have not been specified at the time of writing of SAP 
 
 
Table 90: 
Percentage of Subjects Abstinent from Smoking Weeks 3-6 – Among Baseline Smokers 
Same analysis as Table 88 
 
Table 91: 
Percentage of Subjects Abstinent from Smoking Weeks 3-6 – Full Model Logistic Regression (Among Baseline 
Smokers) 
Same analysis as Table 89 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
91  
Table 92: 
PSQI Scores – mITT Subjects 
 
ASP8062 
 
Placebo 
Study 
Week 
N 
Mean (SD1) 
Median 
(Min-Max) 
N 
Mean (SD) 
Median 
(Min-Max) 
1 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
5 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
7 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
1 SD is standard deviation 
 
Table 93: 
PSQI Scores (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 
Type III Wald Tests 
Parameter 
Num DF1 
Den DF2 
F Value 
p-value 
Arm 
1 
xx 
xxx.xx 
0.xxx 
Site 
xx 
xx 
xxx.xx 
0.xxx 
Baseline PSQI 
1 
xx 
xxx.xx 
0.xxx 
1 Numerator degrees of freedom; 2 Denominator degrees of freedom 
 
 
 
 
Least Squares Means 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
92  
 
 
 
 
95% CI2 
 
 
Model 
Arm 
Week 
Estimate SE1 
Lower CI 
Upper CI Difference 
SE 
p-value Cohen’s d 
ASP8062 
5 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 0.xxx 
xx.xxx 
Placebo 
5 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
ASP8062 
7 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 0.xxx 
xx.xxx 
Placebo 
7 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
1 SE is standard error; 2 CI is confidence interval 
Programming note:If a transformation of the dependent variable is used add 2 columns: p-value and Cohen’s d for the transformed model. 
 
Table 94: 
POMS Total Mood Disturbance Score – mITT 
 
ASP8062 
Placebo 
Study 
Week 
N 
Mean (SD1) 
Median 
(Min-Max) 
N 
Mean (SD) 
Median 
(Min-Max) 
1 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
5 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
7 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
1 SD is standard deviation 
 
 
Table 95: 
POMS Total Mood Disturbance Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 
Type III Wald Tests 
Parameter 
Num DF1 Den DF2 F Value 
 
p-value 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Parameter 
Num DF1 Den DF2 F Value 
 
p-value 
Arm 
1 
xxx 
xxx.xx 
0.xxx 
Week 
1 
xxx 
xxx.xx 
0.xxx 
Site 
2 
xxx 
xxx.xx 
0.xxx 
Cov 
x 
xxx 
xxx.xx 
0.xxx 
Arm*Week 
x 
xxx 
xxx.xx 
0.xxx 
1 Numerator degrees of freedom; 2 Denominator degrees of freedom 
 
 
 
Programming note: Cov is the baseline equivalent of the dependent variable and any additional covariates included in the model. 
 
Least Squares Means 
 
 
 
 
95% CI2 
 
 
Model 
Arm 
Week 
Estimate 
SE1 
Lower CI 
Upper CI 
Difference SE 
p-value 
Cohen’s d 
ASP8062 
4 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 
0.xxx 
xx.xxx 
Placebo 
4 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
ASP8062 
6 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 
0.xxx 
xx.xxx 
Placebo 
6 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
ASP8062 
Overall  
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 
0.xxx 
xx.xxx 
Placebo 
Overall 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
1 SE is standard error; 2 CI is confidence interval 
Programming note:If a transformation of the dependent variable is used add 2 columns: p-value and Cohen’s d for the transformed model. 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
94  
 
 
Table 94 is the template for Tables 96, 98, 100, 102, 104, and 106. Table 95 is the template for Tables 97, 99, 101, 103, 105, and 107 
 
Table 96: 
POMS Tension-Anxiety Score – mITT Subjects 
Table 97: 
POMS Tension-Anxiety Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 
Table 98: 
POMS Anger-Hostility Score – mITT Subjects 
Table 99: 
POMS Anger-Hostility Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 
Table 100: 
POMS Vigor-Activity Score – mITT Subjects 
Table 101: 
POMS Vigor-Activity Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 
Table 102: 
POMS Fatigue-Inertia Score – mITT Subjects 
Table 103: 
POMS Fatigue-Inertia Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 
Table 104 
POMS Confusion-Bewilderment Score – mITT Subjects 
Table 105: 
POMS Confusion-Bewilderment Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 
Table 106: 
POMS Depression-Dejection Score – mITT Subjects 
Table 107: 
POMS Depression-Dejection Score (mITT) – Full Model, Mixed Effects, Weeks 5 & 7 
 
 
 
 
Table 108: 
PROMIS Negative Consequences of Alcohol Scores – mITT Subjects 
 
Placebo 
 
ANS-6637 
200mg 
Study 
Week 
N 
Mean (SD1) 
Median 
(Min-Max) 
N 
Mean (SD) 
Median 
(Min-Max) 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
95  
1 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
7 
xx 
xxx (xx) 
xxx 
(xx-xx) 
xx 
xxx (xx) 
xxx 
(xx-xx) 
1 SD is standard deviation 
 
Table 109: 
ANCOVA PROMIS Negative Consequences of Alcohol – mITT Subjects 
Type III Wald Test 
Parameter 
Num DF1 
Den DF2 
F Value 
p-value 
Arm 
1 
xx 
xxx.xx 
0.xxx 
Site 
2 
xx 
xxx.xx 
0.xxx 
Baseline PROMIS 
1 
xx 
xxx.xx 
0.xxx 
1 Numerator degrees of freedom; 2 Demonimator degrees of freedom 
 
 
 
 
 
 
Least Squares Means 
 
 
 
 
95% CI2 
 
 
Model 
Arm 
Week 
Estimate SE1 
Lower 
CI 
Upper CI Difference 
SE 
p-value Cohen’s d 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
96  
 
 
 
 
95% CI2 
 
 
Model 
Arm 
Week 
Estimate SE1 
Lower 
CI 
Upper CI Difference 
SE 
p-value Cohen’s d 
ASP8062 
7 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
x.xxx 
x.xxx 0.xxx 
xx.xxx 
Placebo 
7 
xx.xx 
0.xxx 
0.xxx 
0.xxx 
 
 
 
 
1 SE is standard error; 2 CI is confidence interval 
Programming note:If a transformation of the dependent variable is used add 2 columns: p-value and Cohen’s d for the transformed model. 
 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
97  
 
12.1.6. 
Safety Analyses


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
98  
Table 110: 
Overall Summary of Adverse Events – Safety Subjects 
 
ASP8062 
Placebo 
Total 
 
 
(N=xx) 
(N=xx) 
(N=xxx) 
p-value1 
Number of AEs 
xx 
xx 
xx 
 
Number of SAEs 
xx 
xx 
xx 
 
Number (%) of subjects with at least one AE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
0.xxx 
Number (%) of subjects with at least one SAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
0.xxx 
Number (%) of subjects with at least one AE related2 to study 
product 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
0.xxx 
Number of AEs by severity 
 
 
 
 
     Mild 
xx 
xx 
xx 
 
     Moderate 
xx 
xx 
xx 
 
    Severe 
xx 
xx 
xx 
 
   Life-threatening 
xx 
xx 
xx 
 
Number of AEs by relationship to study product 
 
 
 
 
     At least possibly related 
xx 
xx 
xx 
 
     Unrelated 
xx 
xx 
xx 
 
Number of AEs by SAE status 
 
 
 
 
     No 
xx 
xx 
xx 
 
      Yes 
xx 
xx 
xx 
 
 
1p-value from chi-square test   2 Related is possible, probable, or definite 
 
Table 111: 
 Number and Percentage of Subjects with Adverse Events - Safety Subjects 
 
MedDRA System Organ Class/ 
ASP8062 
Placebo 
   Preferred Term 
(N=xx) 
(N=xx) 
- Any Adverse Events -  
xx (xx.x%) 
xx (xx.x%) 
SOC 
 
 
   - Overall -  
xx (xx.x%) 
xx (xx.x%) 
      Preferred term 1 
xx (xx.x%) 
xx (xx.x%) 
      Preferred term 2 
xx (xx.x%) 
xx (xx.x%) 
Notes: Percentages are based on the total number of subjects, as given in the column heading. 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
99  
Multiple occurrences of a specific adverse event for a subject are counted once in the frequency for the adverse event. Likewise, multiple occurrences of 
adverse events within a specific preferred term for a subject are counted once in the frequency for the preferred term. 
Programmer’s Notes: Order System Organ Class alphabetically and preferred term alphabetically within System Organ Class. 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
100  
Table 112: 
Summary of Subjects with Adverse Events by Severity and Relationship – ASP8062 
Number of Subjects (%) (N=x)  
 
 
Mild 
Moderate 
Severe 
Life-threatening 
All Grades 
SOC 
MedDRA 
PT 
R 
NR 
R 
NR 
R 
NR 
R 
NR 
R 
NR 
R + NR 
 
 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
Notes: Events are counted once per subject at the highest severity grade and closest relationship to the investigational product. R= related to investigational 
product (possibly, probably, definitely). NR = not related to investigational product (unrelated, unlikely). 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
101  
Table 113: 
Summary of Subjects with Adverse Events by Severity and Relationship – Placebo 
Number of Subjects (%) (N=x)  
 
 
Mild 
Moderate 
Severe 
Life-threatening 
All Grades 
SOC 
MedDRA 
PT 
R 
NR 
R 
NR 
R 
NR 
R 
NR 
R 
NR 
R + NR 
 
 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
Notes: Events are counted once per subject at the highest severity grade and closest relationship to the investigational product. R= related to investigational 
product (possibly, probably, definitely). NR = not related to investigational product (unrelated, unlikely). 
 
 
Table 114: 
Number and Percentage of Subjects with Adverse Events by Maximum Severity - Safety Subjects 
 
MedDRA SOC/ 
ASP8062 
Placebo 
  Preferred Term 
(N=xx) 
(N=xx) 
 
Mild 
Moderate 
Severe 
Life-
threatening 
Mild 
Moderate 
Severe 
Life-
threatening 
- Any Adverse Events -  
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
SOC 
 
 
 
 
 
 
 
 
   - Overall -  
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
      Preferred term 1 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
      Preferred term 2 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
Notes: Percentages are based on the total number of subjects, as given in the column heading. 
Multiple occurrences of a specific adverse event for a subject are counted once in the frequency for the adverse event. Likewise, multiple occurrences of adverse 
events within a specific preferred term for a subject are counted once in the frequency for the preferred term. 
Programmer’s Notes: Order System Organ Class alphabetically and preferred term alphabetically within System Organ Class. 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
102  
Table 115: 
Number and Percentage of Subjects Adverse Events by Relatedness - Safety Subjects 
 
MedDRA SOC/ 
ASP8062 
Placebo 
  Preferred Term 
(n=xx) 
(n=xx) 
 
Related1 
Not-Related2 
Related 
Not-Related 
SOC 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
   - Overall -  
 
 
 
 
      Preferred term 1 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
      Preferred term 2 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
1Related are possibly, probably or definitely related to investigational product 
2 Not Related to investigational product (not related or unlikely) 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
103  
 Table 116: 
Number and Percentage of Subjects with Treatment-Related Adverse Events by Maximum Severity- Safety 
Subjects 
 
MedDRA SOC/ 
ASP8062 
Placebo 
  Preferred Term 
(N=xx) 
(N=xx) 
 
Mild 
Moderate 
Severe 
Life-
threatening 
Mild 
Moderate 
Severe 
Life-
threatening 
SOC 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
   - Overall -  
 
 
 
 
 
 
 
 
      Preferred term 1 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
      Preferred term 2 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
nn (xx.x%) 
 
Notes: Percentages are based on the total number of subjects, as given in the column heading. 
Multiple occurrences of a specific adverse event for a subject are counted once in the frequency for the adverse event. Likewise, multiple occurrences of 
adverse events within a specific preferred term for a subject are counted once in the frequency for the preferred term. 
Programmer’s Notes: Order System Organ Class alphabetically and preferred term alphabetically within System Organ Class. 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
104  
Table 117: 
Number and Percentage of Subjects with Adverse Events Occurring in >= 5% of Subjects in Any One Group - 
Safety Subjects 
 
MedDRA SOC/ 
ASP806 
Placebo 
 
  Preferred Term 
(N=xx) 
(N=xx) 
p-value1 
SOC 
nn (xx.x%) 
nn (xx.x%) 
x.xxx 
   - Overall -  
 
 
 
      Preferred term 1 
nn (xx.x%) 
nn (xx.x%) 
x.xxx 
      Preferred term 2 
nn (xx.x%) 
nn (xx.x%) 
x.xxx 
Notes: Percentages are based on the total number of subjects, as given in the column heading. 
Multiple occurrences of a specific adverse event for a subject are counted once in the frequency for the adverse event. Likewise, multiple occurrences of 
adverse events within a specific preferred term for a subject are counted once in the frequency for the preferred term. At least % occurring in either arm to 
be included in the table. 
1p-value from Fisher’s exact test 
Programmer’s Notes: Order System Organ Class alphabetically and preferred term alphabetically within System Organ Class. 
 
 
 
 
 
 
 
Table 118: 
Number and Percentage of Subjects with Adverse Events Leading to Discontinuation of Study - Safety Subjects 
MedDRA SOC/ 
ASP8062 
Placebo 
  Preferred Term 
(N=xx) 
(N=xx) 
SOC 
 
 
   - Overall -  
nn (xx.x%) 
nn (xx.x%) 
      Preferred term 1 
nn (xx.x%) 
nn (xx.x%) 
      Preferred term 2 
nn (xx.x%) 
nn (xx.x%) 
 
 
 
Notes: Percentages are based on the total number of subjects, as given in the column heading. 
Multiple occurrences of a specific adverse event for a subject are counted once in the frequency for the adverse event. Likewise, multiple occurrences of 
adverse events within a specific preferred term for a subject are counted once in the frequency for the preferred term. 
Programmer’s Notes: Order System Organ Class alphabetically and preferred term alphabetically within System Organ Class. 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
105  
 
 
 
 
Table 119: 
Number and Percentage of Subjects with Adverse Events Leading to Discontinuation of Study Drug – Safety 
Subjects 
MedDRA SOC/ 
ASP8062 
Placebo 
  Preferred Term 
(N=xx) 
(N=xx) 
SOC 
 
 
   - Overall -  
nn (xx.x%) 
nn (xx.x%) 
      Preferred term 1 
nn (xx.x%) 
nn (xx.x%) 
      Preferred term 2 
nn (xx.x%) 
nn (xx.x%) 
Notes: Percentages are based on the total number of subjects, as given in the column heading. 
Multiple occurrences of a specific adverse event for a subject are counted once in the frequency for the adverse event. Likewise, multiple occurrences of 
adverse events within a specific preferred term for a subject are counted once in the frequency for the preferred term. 
Programmer’s Notes: Order System Organ Class alphabetically and preferred term alphabetically within System Organ Class. 
 
 
 
 
 
 
 
 
 
Table 120: 
 CIWA-AR Score > 10 at Least Once During Treatment – Safety Subjects 
 
 
ASP8062 
Placebo 
 
 
 
95% CI2 
 
(N=xx) 
(N=xx) 
p-value1 
Cohen’s h 
Odds Ratio 
OR3 Lower CI 
OR Upper CI 
CIWA-AR Score >= 10 
 
 
 
 
 
 
 
  Never 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
  At Least Once 
xx (xx.x%) 
xx (xx.x%) 
0.xxx 
 
 
 
 
ASP8062 vs Placebo 
 
 
 
0.xx 
xx.xxx 
xx.xxx 
xx.xxx 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
106  
1 Chi-squared test; 2 CI is confidence interval; 3 OR is odds ratio 
 
 
 
 
 
 
 
 
 
 
 
Table 121: 
Summary of Vital Signs and Body Weights – Safety Subjects 
 
 
ASP8062 
 
 
 
 
Placebo 
 
Parameter 
N 
Mean (SD) 
Med 
Min-Max 
N 
Mean (SD) 
Med 
Min-Max 
Vital Sign (units) 
 
 
 
 
 
 
 
 
Screening 
xx 
xx.x (xx.xx) 
xx.x 
(xx.x – xx.x) 
xx 
xx.x (xx.xx) 
xx.x 
(xx.x – xx.x) 
Week 1 
xx 
xx.x (xx.xx) 
xx.x 
(xx.x – xx.x) 
xx 
xx.x (xx.xx) 
xx.x 
(xx.x – xx.x) 
Change from Baseline 
xx 
xx.x (xx.xx) 
xx.x 
(xx.x – xx.x) 
xx 
xx.x (xx.xx) 
xx.x 
(xx.x – xx.x) 
Weeks 2,3,4,5,6,7 
 
 
 
 
 
 
 
 
Programmers note: vital signs include pulse rate, systolic blood pressure, and diastolic blood pressure. Body weight (kg) will also be presented. 
 
Table 122: 
 Summary of ECG Results - Safety Subjects 
 
ASP8062 
Placebo 
Result 
(N=xx) 
(N=xx) 
Screening 
 
 
  Normal 
nn (xx.x%) 
nn (xx.x%) 
  Abnormal, Not Clinically Significant 
nn (xx.x%) 
nn (xx.x%) 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
107  
  Abnormal, Clinically Significant 
nn (xx.x%) 
nn (xx.x%) 
Week 4 
 
 
  Normal 
nn (xx.x%) 
nn (xx.x%) 
  Abnormal, Not Clinically Significant 
nn (xx.x%) 
nn (xx.x%) 
  Abnormal, Clinically Significant 
nn (xx.x%) 
nn (xx.x%) 
Week 7 
 
 
  Normal 
nn (xx.x%) 
nn (xx.x%) 
  Abnormal, Not Clinically Significant 
nn (xx.x%) 
nn (xx.x%) 
  Abnormal, Clinically Significant 
nn (xx.x%) 
nn (xx.x%) 
 
Table 123: 
Summary of Blood Chemistries and Hematology – Safety Subjects 
 
ASP8062 
Placebo 
 
N 
Mean (SD) 
Med 
(Min-Max) 
N 
Mean (SD) 
Med 
(Min-Max) 
  Chemistry (units) 
 
 
 
 
 
 
 
 
Baseline Value 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
Week 4 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
Change from baseline 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
Week 7 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
Change from baseline 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
Programmers note: table will include creatinine, ALT, AST, total bilirubin, alkaline phosphate, albumin, CrCl, GGT,  
RBC,  WBC, hematocrit, hemoglobin, platelets. 
 
Table 124: 
Summary of Urinalysis Continuous Data – Safety Subjects 
 
ASP8062 
Placebo 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
108  
 
N 
Mean (SD) 
Med 
(Min-Max) 
N 
Mean (SD) 
Med 
(Min-Max) 
  Urinalysis (units) 
 
 
 
 
 
 
 
 
Baseline Value 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
Week 4 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
Change from baseline 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
    Week 7 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
Change from baseline 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
xx 
xx.x (xx.x) 
xx.x 
(xx.x-xx.x) 
Programmers note: table will PH, specific gravity, and glucose result, . 
 
 
 
 
 
 
 
 
Table 125: 
Summary of Urine Glucose and Nitrites – Safety Subjects 
 
ASP8062 
Placebo 
 
Positive 
Negative 
Positive 
Negative 
 
n (%) 
n (%) 
n (%) 
n (%) 
Glucose 
 
 
 
 
   Baseline 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Week 4 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Week 7 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Nitrites 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
109  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 126: 
Summary of Urine Protein, Ketones, Billirubin, Leukocyte Esterace, and Blood – Safety Subjects 
   Baseline 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Week 4 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Week 7 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
ASP8062 
Placebo 
 
Baseline 
Week 4 
Week 7 
Baseline 
Week 4 
Week 7 
 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Blood 
 
 
 
 
 
 
   Negative 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Trace 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   1+ 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   2+ 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   3+ 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   4+ 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Ketones 
 
 
 
 
 
 
   Negative 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
110  
 
Programmer 
Note: Billirubin 
and Leukocyte 
Esterace follow the 
same as Protein 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 127: 
Summary of Positive Urine Drug Tests, Preganancy Test or BAC > 0.02 Any Time During the Study– Safety 
Subjects 
Test 
ASP8062 
Placebo 
   Trace 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   1+ (small) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   2+ (medium) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   3+ (large) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Protein 
 
 
 
 
 
 
   Negative 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Trace 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   1+ 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   2+ 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   3+ 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   4+ 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
111  
 
(N=xx) 
(N=xx) 
THC 
xx (xx%) 
xx (xx%) 
Cocaine 
xx (xx%) 
xx (xx%) 
Opioids 
xx (xx%) 
xx (xx%) 
Methamphetamine 
xx (xx%) 
xx (xx%) 
Amphetamine 
xx (xx%) 
xx (xx%) 
MDMA 
xx (xx%) 
xx (xx%) 
Benzodiazapines 
xx (xx%) 
xx (xx%) 
Buprenorphine 
xx (xx%) 
xx (xx%) 
Methadone 
xx (xx%) 
xx (xx%) 
Oxycodone 
xx (xx%) 
xx (xx%) 
Ethylglucuronide (EtG) 
xx (xx%) 
xx (xx%) 
Pregnancy 
xx (xx%) 
xx (xx%) 
BAC > 0.02 
xx (xx%) 
xx (xx%) 
 
Table 128: 
Frequency of Subjects with Suicidal Ideation Any Time During the Study – Safety Subjects 
ASP8062 
Placebo 
p-value 
(N=xx) 
(N=xx) 
 
xx (xx.x%) 
xx (xx.x%) 
0.xxx 
 
 
 
Table 129: 
Return to Baseline ACQ-SF-R Scores – Safety Subjects 
 
ASP8062 
Placebo 
Test 
(N=xx) 
(N=xx) 
Screening 
 
 
Increased Craving, n (%) 
xx (xx%) 
xx (xx%) 
Week 3 
 
 
Increased Craving, n (%) 
xx (xx%) 
xx (xx%) 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
113  
 
12.2. 
Listings


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
114  
 
Listing 1: Subject Disposition - All Subjects 
Subject 
ID  
Date of 
Consent  
Treatment 
Group 
mITT  
Eval- 
uable  
Safety 
Study 
Completion 
(Day) Date of 
Study 
Completion or 
Early 
Withdrawal 
Reason for Early 
Withdrawal 
Subject 
confined  
Start Date/ End 
Date of 
confinement 
xxx 
ddmmmyyyy 
ASP8062 
Yes 
Yes 
Yes 
Yes 
(xx) ddmmmyyyy 
xxxxxx 
Yes 
ddmmmyyyy / 
ddmmmyyyy 
 
 
Placebo 
No 
No 
No 
No 
 
 
No 
 
 
 
None 
 
 
 
 
 
 
 
 
Note: Day is relative to Study Day 0. 
 
 
 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
115  
Listing 2. Enrollment and Randomization – All Consented Subjects 
Subject ID  
Treatment Group 
Did the subject meet all 
eligibility criteria? 
Randomized? 
Date of Randomization 
Kit Number 
xxx 
ASP8062 
Yes 
Yes 
ddmmmyyyy 
xxx 
 
Placebo 
No 
No 
 
 
 
 
 
 
 
 
 
Listing 3: Reason not Eligible – Screen Failures 
Subject ID 
Criterion Type 
Criterion 
xxx 
Inclusion Criteria 
 
 
Exclusion Criteria 
 
 
 
 
 
 
 
 
Listing 4: Protocol Deviations – Safety Subjects 
Subject ID  
Treatment Group 
Deviation Date 
Protocol Deviation 
Details 
xxx 
ASP8062 
ddmmmyyyy 
Subject Failed to Meet the Inclusion/Exclusion 
Criteria 
 
 
Placebo 
 
Source Documentation was Not Available 
 
 
 
 
Pregnancy Test Not Performed 
 
 
 
 
Required study data was not obtained or obtained 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
116  
late due to site error 
 
 
 
Informed Consent Deviation 
 
 
 
 
AE/SAE Reporting Deviation 
 
 
 
 
Other Deviation: 
xxxxxxxxxxxxxxx 
Note: Only subjects with protocol deviation are listed. 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
117  
Listing 5: Subjects Excluded from the Efficacy Analysis or Evaluable Set 
Subject 
ID  
Treatment Group 
Reason for Exclusion from mITT  
 
Reason for Exclusion from Evaluable Set 
xxx 
ASP8062 
xxxxxx 
 
 
Placebo 
 
 
Note: Only subjects excluded from the efficacy analysis or evaluable set are listed. 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
118  
Listing 6: Demographics Data – Safety Subjects 
 
Subject 
ID  
Treatment Group 
Gender 
Age 
(yrs) 
Ethnicity 
 
Race 
 
 
 
 
 
 
xxx 
ASP8062 
Male 
xx 
Hispanic or Latino 
American Indian or Alaska 
Native 
 
Placebo 
Female 
 
Not Hispanic or Latino 
Asian 
 
 
 
 
Unknown 
Native Hawaiian or Other 
Pacific Islander 
 
 
 
 
 
Black or African American 
 
 
 
 
 
White 
 
 
 
 
 
Other 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
Listing 7: Baseline Drinking Characteristics – mITT Subjects 
 
Subject 
ID  
Treatment 
Group 
Drinks/Day 
(Days -1 to -28) 
Drinks/Day  
(Days -1 to -14 
Pre- 
randomization) 
Drinks/ Drinking 
Day  
(Days -1 to -28) 
Drinks/Drinking 
Day (Days -1 to -14 
Pre-randomization) 
Weekly % Heavy 
Drinking Days  
(Days -1 to -28) 
Weekly % Heavy 
Drinking Days 
 (Days -1 to -14  
Pre-
randomization) 
xxx 
ASP8062 
xxx.x 
xxx.x 
xxxx 
xxx.x 
xxx.x 
xxx.x 
 
Placebo 
 
 
 
 
 
 
 
 
Subject 
Treatment 
Weekly %Very 
Weekly % Very 
Weekly % Days 
Weekly % Days 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
119  
ID  
Group 
Heavy Drinking 
Days  
(Days -1 to -28) 
Heavy Drinking 
Days  
(Days -1 to -14 Pre-
randomization) 
Abstinent 
 (Days -1 to -28) 
Abstinent (Days -1 
to -14 Pre-
randomization) 
xxx 
ASP8062 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
 
Placebo 
 
 
 
 
Note: Exclude the three abstinent days during pre-randomization period. 
 
 
 
Listing 8: Baseline Smoking Characteristics – mITT Subjects 
Subject ID  
Treatment Group 
Over the past week, how 
many days did you smoke 
cigarettes? 
How many 
cigarettes on 
average per day? 
Over the past week, how 
many days did you use 
nicotine products? 
xxx 
ASP8062 
None 
xxx 
None 
 
Placebo 
1, 2, 3, 4, 5 
 
1, 2, 3, 4, 5 
 
 
6, 7 
 
6, 7 
 
 
Refused to answer 
 
Refused to answer 
 
 
Listing 9: MINI DSM-5 Disorders – Safety Subjects 
Subject 
ID  
Treatment Group 
Visit Date 
Diagnosis 
Timeframe 
xxx 
ASP8062 
ddmmmyyyy 
xxxxxx 
Current (2 weeks ) 
 
Placebo 
 
 
Past  
 
 
 
 
Recurrent  
Note: Only subjects with a diagnosis of a disorder will be listed. 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
120  
Listing 10: MINI DSM-5 AUD – Safety Subjects 
Subject 
ID  
Treatment 
Group 
Visit Date 
# of Symptoms 
xxx 
ASP8062 
ddmmmyyyy 
xx 
 
Placebo 
 
 
 
Listing 11: Medical History – Safety Subjects 
Subject 
ID  
Treatment Group 
 
Medical History 
Verbatim Term/ 
Preferred Term/ 
SOC 
 
Start Date  
Ongoing 
xxx 
ASP8062 
xxxxxxxxxxx 
ddmmmyyyy 
No 
 
Placebo 
 
 
Yes 
 
 
 
 
 
Programming note: Only identify items that were scored “yes” 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Listing 12: Drinking Goal – mITT Subjects 
Subject 
ID  
Treatment 
Group 
Visit Date 
Time 
What goal have you chosen for 
yourself about drinking by the 
end of the study? 
What might a typical week 
look like at the end of the 
study having achieved 
your goal? (number of 
drinks per day) 
Motivation to 
reach goal 
Confidence to 
reach goal 
xxx 
ASP8062 
ddmmmyyyy 
hh:mm 
To stop drinking 
xx 
xx 
xx 
 
Placebo 
 
 
Reduce drinking but not stop 
 
 
 
 
 
 
 
 
 
 
 
  
Listing 13: Physical Exam – Safety Subjects 
Subject 
ID 
Treatment Group 
 
Exam Date  
 
Finding 
Any abnormal finding 
during the physical 
exam?  
xxx 
ASP8062 
ddmmmyyyy 
xxxxxxxxxxx 
Yes  
 
Placebo 
 
 
No  
 
 
 
 
 
Programming Note: Only report the items that are abnormal 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
122  
Listing 14: Daily and Weekly Standard Drink Units (TLFB) During Treatment – mITT Subjects 
Subject 
ID 
Treatment 
Group 
Week 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
Mean 
drinks/day 
Mean drinks/ 
drinking day 
Heavy 
drinking days 
% days 
abstinent 
xxx 
ASP8062 
1 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
Placebo 
2 
 
 
 
 
 
 
 
 
 
 
 
 
 
3, etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 15: Brief Drinking Questionnaire – mITT Subjects 
 
 
 
 
 
 
 
Subject 
ID  
Treatment 
Group 
Date of 
Assessment 
Date that the last day of non-
missing drinking data was 
collected by TLFB  
This is a period of XX days 
since the last day of drinking 
data that was collected by 
TLFB 
Did the subject 
drink during this 
period? 
How many days 
during this period 
did the subject 
drink? 
xxx 
ASP8062 
ddmmmyyyy 
ddmmmyyyy 
xx 
Yes 
xx 
 
Placebo 
 
 
 
No 
 
 
Subject 
ID  
Treatment 
Group 
Date of 
Assessment 
How many 
alcoholic drinks 
on a typical day? 
How many heavy 
drinking days? 
Maximum number of 
drinks on any one 
day? 
How many days did you 
drink this maximum 
number? 
xxx 
ASP8062 
ddmmmyyyy 
xx 
xx 
xx 
xx 
 
Placebo 
 
 
 
 
 
 
 
Listing 16: Cue Reactivity – mITT Subjects 
Subject 
ID  
Treatment 
Group 
Visit 
Date of 
Assessment 
Assessment 
Time 
Cue 
How strong is 
your craving to 
drink alcohol? 
Having a drink 
would make things 
just perfect 
If I could drink 
alcohol now, I 
would drink it 
xxx 
ASP8062 
Screening 
ddmmmyyyy 
hh:mm 
Water 
xx 
xx 
xx 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
123  
 
Placebo 
Week 2 
 
 
Alcohol  
 
 
 
 
 
Subject 
ID  
Treatment 
Group 
Visit 
Cue 
It would be hard 
to turn down a 
drink right now 
How much did 
you like the 
beverage just 
given to you? 
Sum of first 4 
questions 
xxx 
ASP8062 
Screening 
Water 
xx 
xx 
xx 
 
Placebo 
Week 2 
Alcohol  
 
 
 
 
 
 
 
Listing 17: Drinking Consequences and Craving Scores – mITT Subjects 
 
 
 
 
 
 
 
 
Hyperkatifeia 
Subject 
ID 
Treatment 
Group 
Week 
CIWA-
AR 
ACQ-SF-R 
Pre 
ACQ-SF-R 
Post 
PACS 
PROMIS 
Negative 
Consequences 
Total 
Stress 
Depress
ion 
Irritable 
Pain 
xxx 
ASP8062 
 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 18: Pittsburg Sleep Quality Index Scores – mITT Subjects 
Subject ID 
Treatment Group 
Week 
Total score 
xxx 
ASP8062 
Screening 
xx 
 
Placebo 
Week 6 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Week 7 
 
 
 
 
 
 
Listing 19: Smoking and Other Nicotine Use Data– mITT Subjects 
Subject 
ID  
Treatment Group 
Week 
Visit Date 
Over the past 
week, how many 
days did you 
smoke cigarettes? 
On the days you 
smoked, how 
many cigarettes 
did you smoke on 
average? 
How many days 
use nicotine 
products during 
the past week? 
xxx 
ASP8062 
 
ddmmmyyyy 
x 
xx 
x 
 
Placebo 
 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
125  
Listing 20: MINI AUD– Safety Subjects  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject 
ID  
Treatment 
Group 
Item 
# of Symptoms 
 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
 
xxx 
ASP8062 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
 
 
Placebo 
N 
N 
N 
N 
N 
N 
N 
N 
N 
N 
N 
 
 
 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
 
 
Item # 
List of Items 
1 
a. During the times when you drank alcohol, did you end up drinking more than you planned when you started? 
2 
b. Did you repeatedly want to reduce or control your alcohol use? Did you try to cut down or control your alcohol use, but 
failed? IF YES TO EITHER, MARK YES. 
3 
c. On the days that you drank, did you spend substantial time obtaining alcohol, drinking, or recovering from the effects of 
alcohol? 
4 
d. Did you crave or have a strong desire or urge to use alcohol? 
5 
e. Did you spend less time meeting your responsibilities at work, at school, or at home, because of your repeated drinking? 
6 
f. If your drinking caused problems with your family or other people, did you still keep on drinking? 
7 
g. Were you intoxicated more than once in any situation where you or others were physically at risk, for example, driving a car, 
riding a motorbike, using machinery, boating, etc.? 
8 
h. Did you continue to use alcohol, even though it was clear that the alcohol had caused or worsened psychological or physical 
problems? 
9 
i. Did you reduce or give up important work, social or recreational activities because of your drinking? 
10 
j. Did you need to drink a lot more in order to get the same effect that you got when you first started drinking or did you get 
much less effect with continued use of the same amount? 
11 
K1. When you cut down on heavy or prolonged drinking did you have any of the following: [increased sweating or heart rate; 
hand tremor or “the shakes”; trouble sleeping; nausea or vomiting; hearing or seeing things other people could not see or hear or 
having sensations in your skin for no apparent reason; agitation; anxiety; seizures]  (If yes to 2 or more of these, check yes for 
this question), OR 
 
K2. Did you drink alcohol to reduce or avoid withdrawal symptoms or to avoid being hung over? If K1 or K2 = yes, then score 
as yes. 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
126  
Listing 21. Exit Interview – mITT Subjects 
Subject 
ID  
Treatment 
Group 
Visit Date 
Did you think you 
were receiving the 
study drug or the 
placebo? 
What is your desire to 
please people? 
If you had the 
opportunity in the 
future to take the study 
drug again, would you 
continue to take it for 
more than 5 weeks? 
Did you limit your drinking 
because of flushing (a heat 
reaction or facial redness)? 
 
 
 
 
 
 
 
xxx 
ASP8062 
ddmmmyyyy 
Placebo 
More than average 
Yes  
Yes  
 
Placebo 
 
Study Drug 
Average 
No  
No  
 
 
 
Don’t know 
Less than average 
Refuse to answer  
Refuse to answer  
 
 
 
Refuse to answer 
Refuse to answer 
 
 
 
 
 
 
 
Subject 
ID  
Treatment 
Group 
Visit Date 
Did you limit 
your drinking 
because of nausea 
or other effects? 
Did your 
friends or 
family notice 
flushing? 
If your friends or 
family noticed 
flushing, did this 
change your 
drinking? 
Did you ever miss 
a dose of 
medication to 
avoid these 
effects? 
Did you use any 
other services 
during the study 
to help you reduce 
drinking? 
xxx 
ASP8062 
ddmmmyyyy 
Yes  
Yes  
Yes  
Yes  
Yes  
 
Placebo 
 
No  
No  
No  
No  
No  
 
 
 
Refuse to answer  
Refuse to 
answer  
Refuse to answer  
Refuse to answer  
Refuse to answer  
 
 
 
 
 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
127  
 
 
Listing 22: Drug Exposure from AiCure– mITT Subjects 
 
 
 
Pills Taken 
 
 
Subject 
ID 
Treatment 
Group 
Study 
Week 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Total 
Taken 
Total 
Expected 
xxx 
ASP8062 
1, 2, 3, 4, 
5,6 
x 
x 
x 
x 
x 
x 
x 
xx 
xx 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 23: Drug Accountability – Safety Subjects 
Subject ID 
Treatment Group 
Blister Pack 
# 
Date Dispensed 
Date Returned 
# Pills Returned 
xxx 
ASP8062 
1, 2, 3, 4 
ddmmmyyyy 
ddmmmyyyy 
xx 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
Listing 24: Take Control – mITT Subjects 
 
 
Dates Modules Viewed 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
128  
Subject 
ID 
Treatment Group 
1 
2 
3 
4 
5 
6 
7 
xxx 
ASP8062 
ddmmmyyyy 
ddmmmyyyy 
ddmmmyyyy 
ddmmmyyyy 
ddmmmyyyy 
ddmmmyyyy 
ddmmmyyyy 
 
Placebo 
 
 
 
 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
129  
Listing 25: Adverse Events – Safety Subjects 
 
Notes: Day is relative to Study Day 0. 
 Severity: 1=Mild; 2=Moderate; 3=Severe; 4=Potentially Life-threatening. 
 Relationship: 1= Unrelated; 2=Unlikely; 3=Possibly; 4=Probably; 5=Definitely 
 Action Taken Due to AE: 1=None; 2=Treated with Drugs; 3=Non-drug treatment; 4=ER/Outpatient visit; 5=Hospitalization; 6=Referral for treatment 
 Outcome: 1=Resolved; 2=Recovered with sequelae; 3=Ongoing; 4=Required treatment; 5=Unknown 
 
Programmer’s Note: If “Were any AEs reported?” checkbox=No, then display “None Reported” in the Adverse Event column and SOC/PT column. If an AE 
started and stopped the same day, the duration is 1 day. 
 
 
 
 
Listing 26: Serious Adverse Events – Safety Subjects 
 
Subject 
ID 
Treatment 
Group 
Adverse Event 
(Verbatim) S: 
SOC 
P: PT 
Term 
Start Date/ 
Day 
Stop Date/ 
Day 
 
Duration 
in Days 
Severity 
Relation
-ship 
Actions 
Taken 
Outcome 
Serious 
xxx 
ASP8062 
Verbatim 
ddmmmyyyy/ 
xx  
ddmmmyyyy/ 
xx 
 
1 
1 
1 
1 
Yes 
 
Placebo 
S: xxxx 
xx 
xx 
 
2 
2 
2 
2 
No 
 
 
P: xxxx 
 
 
 
3 
3 
3 
3 
 
 
 
 
 
 
 
4 
4 
4 
4 
 
 
 
 
 
 
 
 
5 
5 
5 
 
 
 
 
 
 
 
 
 
6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject 
ID  
Treatment 
Group 
SAE 
Verbatim 
S: SOC 
P: PT 
Start Date/ 
Day 
Stop Date/ 
Day 
SAE Category 
SAE 
Description 
Relevant 
tests/ 
laboratory 
data 
 
 
 
 
 
 
 
 
xxx 
ASP8062 
Verbatim 
ddmmmyyyy 
ddmmmyyyy 
Results in Death 
 
xxxxxx 
 
Placebo 
S: XXX 
Xx 
Xx 
Life-threatening 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
130  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject 
ID 
SAE 
Date of death 
Cause of death 
Hospitalization 
Date/Discharge 
Date 
Comments 
 
 
 
 
 
 
xxx 
Verbatim 
ddmmmyyyy 
xxxxxx 
ddmmmyyyy 
xxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
ddmmmyyyy 
 
 Notes: Day is relative to Study Day 0. 
Severity: 1=Mild; 2=Moderate; 3=Severe; 4=Potentially Life-threatening. 
Relationship: 1= Unrelated; 2=Unlikely; 3=Possibly; 4=Probably; 5=Definitely 
Outcome: 1=Recovered/Resolved; 2=Recovering/Resolving; 3=Not Recovered/Not Resolved; 4=Recovered/Resolved With Sequelae; 5=Fatal (Date of Death) 
 
 
 
 
 
P: XX 
 
 
Requires or Prolongs 
Hospitalization 
 
 
 
 
 
 
 
Disability 
 
 
 
 
 
 
 
Congenital Anomaly/Birth 
Defect 
 
 
 
 
 
 
 
Required Intervention to Prevent 
Persistant or Significant 
Disability / Incapacity 
 
 
 
 
 
 
 
Other 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
131  
Listing 27: POMS Scores – mITT Subjects 
 
 
 
Scores 
Subject 
ID 
Treatment 
Group 
Week 
Total Mood 
Disturbance  
Tension  
Depression  
Anger 
Fatigue 
Confusion  
Vigor  
 
 
 
 
 
 
 
 
 
 
xxx 
ASP8062 
 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
132  
Listing 28. Columbia-Suicide Severity Scale – Safety Subjects 
 
 
 
 
Response to Question: 
 
 
 
 
 
 
 
 
Subject 
ID  
Treatment 
Group 
Visit Date 
Study 
Week 
Q1 
Q2 
Q3 
Q4 
Q5 
Q6 
Q7 
Q8 
Q9 
Q10 
Q11 
Q12 
Q13 
xxx 
ASP8062 
ddmmmyyyy 
 
Yes 
Yes 
Yes 
Yes 
Yes 
Yes 
Type 1 
1 
1 
0 
0 
0 
Yes 
 
Placebo 
 
 
No 
No 
No 
No 
No 
No 
Type 2 
2 
2 
1 
1 
1 
No 
 
 
 
 
 
 
 
 
 
 
Type 3 
3 
3 
2 
2 
2 
 
 
 
 
 
 
 
 
 
 
 
Type 4 
4 
4 
3 
3 
3 
 
 
 
 
 
 
 
 
 
 
 
Type 5 
5 
5 
4 
4 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5 
5 
5 
 
Suicide Ideation 
1. Have you wished you were dead or wished you could go to sleep and not wake up? 
2. Have you actually had any thoughts of killing yourself? 
3. Have you been thinking about how you might do this? 
4. Have you had these thoughts and had some intention of acting on them? 
5. Have you started to work out or worked out the details of how to kill yourself? 
6. Do you intend to carry out this plan? 
Intensity of Ideation 
7. The following features should be rated with respect to the most severe type of ideation (i.e. 1-5 with 1 being the least severe and 5 being the 
most severe) 
8. How many times have you had these thoughts?1=Less than once a week; 2=Once a week;  3=2-5 times a week;  4=Daily or almost;  
5=Many times each day 
9. When you have the thoughts, how long do they last? 1=Fleeting-few seconds or minutes; 2=Less than 1 hr-some of the time;  3=1-4 hrs/a lot of 
time;  4=4-8 hrs/most of day;  5=More than 8 hours/persistent or continuous 
10. Could/can you stop thining about killing yourself or wanting to die if you want to?  1=Easily; 2=Little Difficulty; 3=Some Difficulty; 
4=Lot of Difficulty;  5=Unable to control; 0=Does not attempt to control 
11. Are there things that stop you from wanting to die or acting on thoughts of committing suicide? 1=Definite deterrents; 2=Probably Deterrents;  
3=Uncertain Deterrents; 4=Unlikely Deterrents; 5=No Deterrents; 0=Does not apply 
12. What sort of reasons did you have for thinking about wanting to die or killing yourself? Was it to end pain or stop the way you were feeling or to 
get attention, revenge or reaction from others 1=Completely to get attention or revenge or reaction; 2=Mostly to get attention or revenge or 
reaction; 3=Equally to get attention or revenge or reaction and stop pain; 4=Mostly to stop pain; 5=Completely to stop pain; 0=Does not apply 
Suicidal Behavior 
13. Have you made a suicide attempt? 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
133  
 
 
 
Response to Question: 
 
 
 
 
 
 
 
Subject 
ID 
Treatment 
Group 
Study 
Week 
Q14 
Q15 
Q16 
Q17 
Q18 
Q19 
Q20 
Q21 
Q22 
Q23 
Q24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
ASP8062 
 
xx 
Yes 
Yes 
xx 
Yes 
xx 
Yes 
Yes 
Yes 
0 
0 
 
Placebo 
 
 
No 
No 
 
No 
 
No 
No 
No 
1 
1 
 
 
 
 
 
 
 
 
 
 
 
 
2 
2 
 
 
 
 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
5 (date ddmmmyyyy) 
 
14. Number of attempts 
15. Has the subject engaged in non-suicidal self-injurious behavior? 
16. Has there been a time when you started to do something to end your life but someone or something stopped you before actually did anything? 
17. Number interrupted 
18. Has there been a time when you stared to do something to try to end your life but you stopped yourself before you actually did anything? 
19. Number aborted 
20. Have you taken any step towards making a suicide attempt or preparing to kill yourself? 
21. Suicidal behavior was present during the assessment period 
22. Completed suicide? 
23. Actual Lethality/Medical Damage;  0=No physical damage; 1=Minor physical damage; 2=Moderate physical Damage; 3=Moderately severe physical 
damage; 4=Severe physical damage; 5=Death 
24. Potential Lethality;  0=Behavior not likely to result in injury; 1=Behavior likely to result in injury, but not death; 2=Behavior likely to result in death 
 
Listing 29: Blood Chemistries – Safety Subjects 
Subject 
ID  
Treatment Group 
Visit Date 
Test Name 
Result 
Units 
Flag 
Evaluation 
xxxx 
ASP8062 
ddmmmyyyy 
Creatinine 
x.xx 
mg/dL 
H (high) 
WNL 
 
Placebo 
 
Total Bilirubin 
xxx 
mg/dL 
L (low) 
Abnormal, NCS 
 
 
 
ALT 
xx.x 
U/L 
 
Abnormal, CS 
 
 
 
AST 
x.xx 
U/L 
 
 
 
 
 
BUN 
Xx 
mg/dL 
 
 
 
 
 
Creatinine Clearance 
xxx.xx 
mL/min 
 
 
 
 
 
Akaline Phosphate 
xxx.x 
U/L 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
134  
Subject 
ID  
Treatment Group 
Visit Date 
Test Name 
Result 
Units 
Flag 
Evaluation 
 
 
 
Albumin 
xx.x 
g/dL 
 
 
 
 
 
GGT 
xx.x 
U/L 
 
 
 
 
 
Total Cholesterol 
xxx 
mg/dL 
 
 
 
 
 
Triglycerides 
xx 
mg/dL 
 
 
 
 
 
Chloride 
xxx 
mmol/L 
 
 
 
 
 
Sodium 
xxx 
mmol/L 
 
 
 
 
 
Potasium 
xx.x 
mmol/L 
 
 
 
 
Listing 30: Hematology – Safety Subjects 
Subject 
ID  
Treatment 
Group 
Visit Date 
Test Name 
Result 
Units 
xxxx 
ASP8062 
ddmmmyyyy 
Hematocrit 
xxx.xx 
% 
 
Placebo 
 
Hemoglobin 
xxx 
g/dL 
 
 
 
RBC 
xx.x 
mil/uL 
 
 
 
WBC 
x.xx 
thous/uL 
 
 
 
Platelets 
xxx.xx 
thous/uL 
 
 
 
Neutrophils 
xxx.x 
% 
 
 
 
Monocytes 
xx.x 
% 
 
 
 
Eosinophils 
xx.x 
% 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
135  
Subject 
ID  
Treatment 
Group 
Visit Date 
Test Name 
Result 
Units 
 
 
 
Basophils 
xx.x 
% 
 
 
 
Listing 31: Urinalysis – Safety Subjects 
Subject 
ID  
Treatment 
Group 
Visit Date 
Study 
Week 
pH 
Specific 
Gravity 
Glucose 
Glucose 
Result 
(mg/dL) 
Protein 
Ketones 
Blood 
Nitrites 
Bilirubin 
Leukocyte 
Esterase 
xxx 
ASP8062 
ddmmmyyyy 
Screen 
xx.x 
x.xxx 
Negative 
xxxx 
Negative 
Negative 
Negative 
Negative 
Negative 
Negative 
 
Placebo 
 
x 
 
 
Positive 
 
Trace 
Trace 
Trace 
Positive 
Trace 
Trace 
 
 
 
 
 
 
 
 
1+ 
1+ 
1+ 
 
1+ 
1+ 
 
 
 
 
 
 
 
 
2+ 
2+ 
2+ 
 
2+ 
2+ 
 
 
 
 
 
 
 
 
3+ 
3+ 
3+ 
 
3+ 
3+ 
 
 
 
 
 
 
 
 
4+ 
4+ 
4+ 
 
4+ 
4+ 
 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
136  
 
Listing 32: Urinalysis Microscopy1 – Safety Subjects 
Subject 
ID  
Treatment 
Group 
Visit Date 
Test Name 
Result (cells/HPF) 
xxxx 
ASP8062 
ddmmmyyyy 
Microscopic RBC 
xx 
 
Placebo 
 
Microscopic WBC 
xx 
 
 
 
Epithelial Cells 
xx 
 
 
 
Hyaline Casts 
xx 
1Only subjects that had microscopy 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
137  
Listing 33: Pregnancy Test/Birth Control Data – Safety Subjects 
Subject 
ID  
Treatment Group 
Gender 
Pregnancy Test 
Performed? 
 
Pregnancy Test / 
Visit Date 
Pregnancy Result 
Methods of birth control 
xxx 
ASP8062 
Male 
Not Done 
ddmmmyyyy 
Negative 
Oral Contraceptive 
 
Placebo 
Female 
Yes 
 
Positive 
Vasectomy 
 
 
 
 
 
 
Contraceptive Skin Patch 
 
 
 
 
 
 
Intrauterine 
 
 
 
 
 
 
Medroxyprogesterone 
 
 
 
 
 
 
Complete Abstinence 
 
 
 
 
 
 
Tubal Ligation or Postemopausal 
 
 
 
 
 
 
Other : xxxxxxxxxxxxxxxx 
  Programming note: Only indicate birth control methods that were indicated as Yes 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
138  
Listing 34: Blood Alcohol Concentration – Safety Subjects 
Subject 
ID  
Treatment 
Group 
Visit Date 
Study 
Week 
BAC 
Performed 
Time of 
BAC 
BAC % 
 
 
 
 
 
 
 
xxx 
ASP8062 
ddmmmyyyy 
x 
Done  
hh:mm 
x.xxx 
 
Placebo 
 
 
Not Done  
 
 
 
 
Listing 35. Urine Drug Screen – Safety Subjects 
Subject ID  
Treatment 
Group 
Visit Date 
Study 
Week 
AMP1 
Benzos2 
Coc3 
Bup4 
Meth5 
Methadone 
Opioids 
THC 
Barb6 
MDMA 
EtG7 
xxx 
ASP8062 
ddmmmyyyy 
Screen 
Neg 
Neg 
Neg 
Neg 
Neg 
Neg 
Neg 
Neg 
Neg 
Neg 
Neg 
 
Placebo 
 
x 
Pos 
Pos 
Pos 
Pos 
Pos 
Pos 
Pos 
Pos 
Pos 
Pos 
Pos 
1AMP = Amphetamine; 2Benzos = Benzodiazapines; 3 Coc = Cocaine; 4 Bup = Buprenorphine; 5 Methamphetamine; 6Barb = Barbituates; 
7 EtG = Ethyl Glucuronide; Note: Neg=negative; Pos=positive 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
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Listing 36: Vital Signs and Body Weights– Safety Subjects 
 
 
Listing 37. ECG – Safety Subjects 
Subject ID  
Treatment Group 
Visit Date 
Study 
Week 
Result 
If abnormal, specify finding  
xxx 
ASP8062 
ddmmmyyyy 
Screen 1 
Normal 
xxxxxxxxxxx 
 
Placebo 
 
x 
Abnormal, NCS 
 
 
 
 
 
Abnormal, CS 
 
 
 
 
 
 
Listing 38. Prior and Concomitant Medications – Safety Subjects 
Subject 
ID 
Treatment 
Group  
Prohibited 
Med 
Verbatin Med  
Indication 
Route  
Frequency 
Dose  
Start Date/ 
Stop Date  
Study Day  
Continuing?  
xxx 
ASP8062 
Yes  
xxx  
xxxxxx 
xxxxxx  
xxxxxx 
xxxxxx  
ddmmmyyyy 
xxx 
Yes  
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
No  
xxx  
 
 
 
 
 
 
No  
Prohibited meds include CYP3A4 inhibitors, CYP3A4 inducers, Benzodiazepines sedatives/hypnotics/anxiolytics, Monoamine oxidase inhibitors, Opioids, 
Opioid partial agonist-antagonists/opioid antagonists, and Drugs approved or have clinical data supporting their use for the treatment of AUD. 
Subject ID  
Treatment 
Group 
Visit Date 
Study 
Week 
Weight (Kg) 
Heart Rate 
(beats/min) 
Systolic Pressure 
(mmHg) 
Diastolic Pressure 
(mmHg) 
xxx 
ASP8062 
ddmmmyyyy 
Screening  
xxx 
xxx 
xxx 
xxx 
 
Placebo 
 
x 
 
 
 
 


 
Statistical Analysis Plan: Protocol HLAB-003, Version 6.0  Dated: 13Jun2022 
140  
 
 
Listing 39: Blood for Drug Concentrations – Safety Subjects 
Subject 
ID 
Treatment 
Group  
Sample 
Collected? 
Date  
Time 
ASP8062 Plasma 
Level (ng/mL) 
AS3486189 Plasma 
Level (ng/mL) 
AS3486191 
Plasma Level 
(ng/mL) 
AS3486192 
Plasma Level 
(ng/mL) 
xxx 
ASP8062 
Yes  
ddmmmyyyy 
hh:mm 
xxx 
xxx 
xxx 
xxx 
 
Placebo 
No 
 
 
 
 
 
 
 
 
 
 
Listing 40: Comments – Safety Subjects 
Subject ID 
Treatment Group 
Comments  
 
 
 
xxx 
ASP8062 
 xxxxxxxxxxxxxx 
 
Placebo 
 
 
 


 
 
141 
 
12.3. 
Figures 
 
 


 
 
142 
 
 
Figure 1: 
Percentage of Subjects No Heavy Drinking Days Weeks 3-6  
 
Programmer note: Use percent on y-axis, bar graph of PSNHDD add Cohen’s h, * a significant p-value, put values on graph 
 
Figure 2: 
Percentage of Subjects Abstinent Weeks 3-6  
 
Programmer note: bar graph of PSA add Cohen’s h, * a significant p-value, put values on graph 
 
 
Figure 3: 
Weekly Percentage of Subjects No Heavy Drinking Days (mITT) 
Programmer note: graph of estimates out to 5 weeks. Include 95% confidence intervals for each estimate and * on statistically significant differences between 
treatment groups. 
Figure 4: 
Weekly Percentage of Subjects Abstinent (mITT) 
 
Figure 5: 
Weekly Percentage WHO 1-Level Decrease in Alcohol Consumption (mITT) 
Figure 6: 
Weekly Percentage WHO 2-Level Decrease in Alcohol Consumption No Imputation (mITT) 
Figure 7: 
Percentage Days Abstinent per Week Least Squares Means – (mITT) 
Figure 8: 
Percent Heavy Drinking Days per Week Lease Squares Means –(mITT) 
Figure 9: 
Mean Drinks per Week Lease Squares Means – (mITT) 
Figure 10: 
Mean Drinks per Drinking Day by Week Least Squares Means –  (mITT) 
Figure 11: 
Weekly Number of Cigarettes Smoked in Smokers Over Entire Treatment Period – Least Squares Means 
(mITT) 
Figure 12: 
Clinical Chemistry, Urinalysis, and Hematology Values Over Time