Clinical trial NCT05487404
Conditions: Ethanol Intoxication
Keywords: Aldeyra ADX-629
Sponsor: Aldeyra Therapeutics, Inc.
Start date: 2021-11-15; Completion date: 2022-05-29
Enrollment: 26 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
A Double-Blind Trial to Assess the Interaction Between ADX-629 and Ethanol While Exploring the Safety, Tolerability, and Activity of ADX-629 in Subjects With Elevated Ethanol Levels

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: ADX-629 intervention 2: Placebo
Intervention descriptions: intervention 1: 3 oral doses of ADX-629 600 milligrams intervention 2: 3 oral doses of placebo

Protocol documents:
Prot_000.pdf: 
 
 
CLINICAL STUDY PROTOCOL 
 
A Double-Blind Phase 1b Study to Assess the Interaction Between 
ADX-629 and Ethanol While Exploring the Safety, Tolerability, and 
Activity of ADX-629 in Subjects With Elevated Ethanol Levels 
Investigational Product: ADX-629  
Protocol Number: ADX-629-ET-001 
 
 
Sponsor: 
Aldeyra Therapeutics, Inc. 
131 Hartwell Avenue, Suite 320 
Lexington, MA 02421 
United States 
Telephone: 781-761-4904 
Fax: 339-674-6495 
 
 
Version Number: 3.0 
Original Protocol: 17 August 2021 
Amendment 1: 01 October 2021 
Amendment 2: 16 March 2022 
 
 
 
Confidentiality Statement 
The information in this document is confidential and is not to be disclosed without the written 
consent of Aldeyra Therapeutics, Inc. except to the extent that disclosure would be required by 
law and for the purpose of evaluating and/or conducting a clinical study for Aldeyra 
Therapeutics, Inc. You are allowed to disclose the contents of this document only to your 
Institutional Review Board and study personnel directly involved with conducting this protocol. 
Persons to whom the information is disclosed must be informed that the information is 
confidential and proprietary to Aldeyra Therapeutics, Inc. and that it may not be further disclosed 
to third parties. 




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INVESTIGATOR AGREEMENT 
By signing below, I agree that: 
I have read this protocol. I approve this document and I agree that it contains all necessary details 
for carrying out the study as described. I will conduct this study in accordance with the design and 
specific provision of this protocol and will make a reasonable effort to complete the study within 
the time designated. I will provide copies of this protocol and access to all information furnished 
by Aldeyra Therapeutics, Inc. to study personnel under my supervision. I will discuss this material 
with them to ensure they are fully informed about the study product and study procedures. I will 
let them know that this information is confidential and proprietary to Aldeyra Therapeutics, Inc. 
and that it may not be further disclosed to third parties. I understand that the study may be 
terminated or enrollment suspended at any time by Aldeyra Therapeutics, Inc., with or without 
cause, or by me if it becomes necessary to protect the best interests of the study subjects. 
I agree to conduct this study in full accordance with Food and Drug Administration Regulations, 
Institutional Review Board/Ethic Committee Regulations, and International Council for 
Harmonisation Guidelines for Good Clinical Practices. 
 
 
 
 
 
 
______________________________________________  
____________________ 
Investigator’s Signature 
 
 
 
 
 
Date 
 
 
 
______________________________________________ 
Investigator’s Printed Name 
 


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SYNOPSIS 
TITLE: A Double-Blind Phase 1b Study to Assess the Interaction Between ADX-629 and 
Ethanol While Exploring the Safety, Tolerability, and Activity of ADX-629 in Subjects With 
Elevated Ethanol Levels 
PROTOCOL NUMBER: ADX-629-ET-001 
INVESTIGATIONAL PRODUCT: ADX-629 
PHASE: 1b 
INDICATION: Elevated ethanol levels 
OBJECTIVE: 
The primary objective is to assess the interaction between ADX-629 and ethanol while exploring 
the safety, tolerability, and activity of ADX-629 in subjects with elevated ethanol levels. 
POPULATION: 
Inclusion Criteria: 
Subjects meeting all of the following criteria will be considered eligible for the study: 
 Male or female subjects between the ages of 21 and 65 years, inclusive, at Screening; 
 
 
 
 Subjects with the ability to obtain transportation to and from the study site; 
 Subjects with a history of alcohol-related symptoms or negative symptomatology following 
the consumption of 4 alcoholic beverages; 
Note: Alcohol-related symptoms may include any of the following: headache, flushing, 
fatigue, diarrhea, nausea, dizziness, confusion/disorientation, or nystagmus. 
 
 
  
 Subjects who agree to avoid use of prescription or over-the-counter medications, including 
topicals, herbal supplements, dietary supplements (excluding fish oil), or nutraceuticals 
within 14 days prior to Screening until the end of the study; 
Note: Subjects must avoid oral contraceptives from within 7 days prior to Screening until 
the end of the study and immunomodulators (eg, corticosteroids, cytokine inhibitors, and 
Janus kinase inhibitors) from within 60 days prior to Screening until the end of the study. 
 Subjects (all females of childbearing potential [FCBPs] and males with a female partner of 
childbearing potential) who agree to use an effective form of contraception (nonhormonal or 
barrier method) during the study and for 7 days after the last dose of study drug; 


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Note: An FCBP is defined as any female, regardless of sexual orientation, who has not 
undergone a hysterectomy, bilateral oophorectomy, salpingectomy, or bilateral tubal ligation 
or has not been naturally postmenopausal for at least 12 consecutive months (ie, has had 
menses at any time in the preceding 12 consecutive months) with a negative 
follicle-stimulating hormone (FSH) test. An FSH test will be performed at Screening in all 
naturally postmenopausal women to confirm menopausal status. 
Note: Sperm donation is also prohibited during the study and for 90 days after the last dose 
of study drug. 
 Subjects who are willing to consume the standardized alcohol preparation; 
 
 
 
 
 
 Subjects who agree to abstain from consumption of non-study alcohol during the study. 
Exclusion Criteria: 
Subjects meeting any of the following criteria will be excluded from the study: 
 
 
 
 
 
 
 Subjects with abnormal laboratory values of clinical significance, at the discretion of the 
Investigator, at Screening; 
Note: 1 repeat of laboratory assessments is allowed to confirm abnormal values. 
 
 
 
 
 Subjects with a history of or active: 
o Reactive airway disease; 
o Diabetes; 
o Kidney or bladder stones; 
o Kidney disease (including past or current dialysis requirement); 
o Liver disease; 
o Stomach ulcer; 
o Organ transplant; 
o Gastric bypass; or 
o Any other medical/surgical condition of clinical significance, at the discretion of the 
Investigator. 
 Subjects with nicotine product use within 14 days prior to Screening until the end of the 
study; 


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 Subjects with any history of or current alcohol or other substance use disorder diagnosed 
according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition; 
 Subjects with a positive urine drug screen or breath alcohol test at Screening or Check-In 
(both treatment periods); 
 
 
 
 Subjects who are currently pregnant or lactating or plan to become pregnant during the study; 
Note: A serum pregnancy test will be performed in all FCBPs at Screening and a urine 
pregnancy test will be performed at Check-In (both treatment periods). 
 Subjects who are positive for HIV antibody, hepatitis C virus antibody, hepatitis B virus 
surface antigen, or severe acute respiratory syndrome coronavirus-2 RNA; 
 Subjects who have participated in any other investigational study within the past 30 days or 
within 5 half-lives of the investigational therapy, whichever is longer, at Screening; 
 Subjects currently taking or who cannot abstain from corticosteroids, cytokine inhibitors, 
Janus kinase inhibitors, and/or nonsteroidal anti-inflammatory drugs; or 
 Subjects currently taking or who cannot abstain from medications that can cause a 
disulfiram-like reaction (eg, metronidazole) or who have taken such medications within the 
past 30 days at Screening. 
STUDY DESIGN AND DURATION: 
ADX-629-ET-001 is a Phase 1b, single-center, double-blind, placebo-controlled, randomized, 
crossover study to assess the interaction between ADX-629 and ethanol while exploring the 
safety, tolerability, and activity of ADX-629 in subjects with elevated ethanol levels. 
Approximately 30 subjects are expected to be enrolled in the study. 
This study will utilize a 2-sequence, 2-period, 2-way crossover design. Subjects will be 
randomized to 1 of 2 treatment sequences (AB or BA) on Day 1 of Treatment Period 1.  
 Treatment A: 3 oral doses of ADX-629 600 mg (2 × 300 mg) oral tablets; and 
 Treatment B: 3 oral doses of matching placebo. 
Study procedures will be completed during the following periods: 
 A Screening Period (Day -28 to -2); 
 Two 3-day inpatient periods (Treatment Periods 1 and 2) (from Check-In through completion 
of treatment period), each consisting of the following: 
o Check-In: Subjects will be admitted to the study site on the day prior to dosing in each 
treatment period. Baseline symptom and sign assessments (except for the Clinical Global 
Impression [CGI]-Improvement Scale) will be completed, and subjects will then be 
housed overnight where they will be required to adhere to a standardized high-fat, 
high-sucrose diet; 
Note: Subjects will be reminded at the beginning of each treatment period that this study 
is placebo-controlled. The placebo-control reminder text will be read as follows: “You 


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are participating in a placebo-controlled study, which means that you will not know if 
you are taking a sugar pill or a drug pill. It is important that you try not to decide whether 
you have taken a sugar pill or a drug pill. Any questions that you answer about how you 
are feeling should not be influenced by whether or not you believe you have taken a 
sugar pill or a drug pill. Please answer questions about how you are feeling as if you had 
not taken any pill at all.” 
o Day 1: 1 dose of study drug will be administered at approximately 4:30 pm followed by 
standardized ethanol consumption as outlined in the manual, and then 1 dose of study 
drug will be administered at approximately 7 pm followed by continued standardized 
ethanol consumption to reach a target blood alcohol concentration (BAC) of 
0.14 g/100 mL, measured via breathalyzer. For more details on the breathalyzer 
measurements, refer to the Study Procedures Manual. Symptom and sign assessments 
(with the exception of the CGI-Improvement Scale) will be evaluated and should be 
completed as soon as practical after target BAC is reached. Study procedures will be 
reviewed for randomized subjects, and, based on the emerging data, the standardized 
ethanol solution and/or BAC testing methods may be modified as needed to ensure target 
BAC is reached within a 4-hour window for the remaining subjects; and 
Note: Subjects will be observed for safety during the treatment periods by study site 
personnel who will be present to assist subjects at all times; there will be a minimum 
requirement of at least 2 study site personnel to assist subjects during their assessments. 
Safety measures will be in place to prevent falling. 
Note: Ethanol will be administered in a standardized oral solution. For more details on 
the consumption guidelines, refer to the Study Procedures Manual. 
o Day 2: 1 dose of study drug will be administered at approximately 8 am, and symptom 
and sign assessments (including the CGI-Improvement Scale) will be completed at 
approximately 7 am, 10 am, and 1 pm. Subjects will be discharged from the study site 
after completion of study procedures (approximately 12 hours after the last dose of study 
drug). Prior to discharge, vital signs will be measured. Subjects will have to achieve a 
BAC of 0.00 g/100 mL as measured by a breathalyzer before discharge. 
 A follow-up telephone call will occur 3 days (1 day) after completion of Treatment 
Period 2. 
For subjects who are withdrawn from the study prior to completion, study procedures will be 
performed at an Early Termination Visit. 
There will be at least a 14-day washout period between the last dose of study drug in Treatment 
Period 1 and the first dose of study drug in Treatment Period 2. Subjects will need to refrain 
from drinking alcohol during the washout period.  
An individual subject’s participation in the study is estimated to be approximately 41 days. 
DOSAGE FORMS AND ROUTE OF ADMINISTRATION: 
Aldeyra Therapeutics, Inc. will supply sufficient quantities of study drug (ADX-629 and 
matching placebo) to allow for completion of the study. The lot numbers will be recorded in the 
final Clinical Study Report. 


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ENDPOINTS:  
The study is not formally powered and all endpoints are exploratory in nature. 
The primary exploratory efficacy endpoints include the following: 
 Assessment of symptoms using the Global Impression Visual Analog Scale, 
CGI-Impairment Severity Scale, CGI-Improvement Scale, and the Alcohol Toxicity 
Symptom Scale;  
 Assessment of signs, determined by evaluation of the following: 
o Objective flushing and ocular redness scales (via digital photography); and 
o Proprioception tests (Romberg Test [time of up to 60 seconds], One Leg Stand Test [time 
of up to 60 seconds], Straight-Line Heel-to-Toe Test [up to 100 steps]). 
 Assessment of ADX-629 activity, determined by evaluation of the following 
pharmacodynamic (PD) markers, for both treatment periods, on Day 1 pre-dose, on Day 1 
one hour after the target BAC is achieved, and on Day 2 one hour after the last dose of study 
drug: 
o 4-hydroxynonenal (HNE), acetaldehyde, malondialdehyde-acetaldehyde adduct (MAA), 
and malondialdehyde (MDA) plasma concentrations; and 
o Plasma cytokine concentrations including, but not limited to, interferon gamma, 
interleukin (IL)-1b, IL-10, IL-12, and IL-17. 
The primary safety endpoint is the safety and tolerability of ADX-629, determined by evaluation 
of the following: 
 Adverse events; 
 Physical examinations; 
 Vital signs (blood pressure, heart rate, respiratory rate, temperature, and oxygen saturation); 
 12-lead electrocardiograms; 
 BAC; 
 Clinical laboratory assessments (including chemistry, hematology, and urinalysis); and 
 Lipid panel evaluations. 
STATISTICAL ANALYSES: 
The Safety Population is defined as all randomized subjects who receive at least 1 dose of study 
drug. 


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The PD Population is defined as all subjects who have at least 1 PD measurement. 
In general, categorical variables will be summarized by the count and percentage of subjects. 
Continuous variables will be summarized by the number of non-missing observations, mean, 
standard deviation, median, minimum, and maximum values. 
In general, the comparison of change from baseline in endpoints over time between the 
2 treatment sequences will be assessed by a mixed effect model for repeated measures. The 
model will include change from baseline as the dependent variable with sequence, period, 
timepoint, treatment, and the interaction of treatment by timepoint as fixed effects, and baseline 
as a covariate. 
 
 
 
 
Efficacy data will also be listed and summarized descriptively. 
Demographic and baseline data will be listed and summarized descriptively. 
Safety and tolerability assessments will be listed and summarized descriptively as the 
observations and, when appropriate, as the change from baseline, and shift tables will be 
produced. 
The statistical analyses to be performed will be further outlined in the Statistical Analysis Plan 
(SAP). The SAP will supersede the protocol if there are any differences between the 2 documents 
in the plans for data analysis, and these differences will be noted in the SAP. 
SAMPLE SIZE DETERMINATION: 
Approximately 30 subjects are expected to be enrolled in the study. The sample size is not based 
on statistical considerations and is not formally powered as all endpoints are exploratory in 
nature.  
SITES: 1 study site in the United States 
SPONSOR: 
Aldeyra Therapeutics, Inc. 
131 Hartwell Avenue, Suite 320 
Lexington, MA 02421 
United States 
Telephone: 781-761-4904 
Fax: 339-674-6495 


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TABLE OF CONTENTS 
Signature Page ................................................................................................................................ 2 
Investigator Agreement ................................................................................................................... 3 
Synopsis .......................................................................................................................................... 4 
Table of Contents .......................................................................................................................... 10 
List of Abbreviations and Definition of Terms............................................................................. 13 
1  Introduction and Background Information ............................................................................. 15 
1.1 
Background ................................................................................................................... 15 
1.1.1  Nonclinical Studies of ADX-629 ...................................................................... 16 
1.1.2  Clinical Studies of ADX-629 ............................................................................ 16 
1.2 
Rationale ........................................................................................................................ 17 
1.3 
Risk/Benefit ................................................................................................................... 17 
2  Study Objective ....................................................................................................................... 18 
2.1 
Primary Objective ......................................................................................................... 18 
3  Study Description.................................................................................................................... 19 
3.1 
Summary of Study Design ............................................................................................ 19 
3.2 
Study Indication ............................................................................................................ 20 
4  Selection and Withdrawal of Subjects .................................................................................... 21 
4.1 
Inclusion Criteria ........................................................................................................... 21 
4.2 
Exclusion Criteria .......................................................................................................... 22 
4.3 
Withdrawal Criteria ....................................................................................................... 23 
4.4 
Rescreening ................................................................................................................... 24 
5  Study Treatments .................................................................................................................... 25 
5.1 
Treatment Groups .......................................................................................................... 25 
5.2 
Rationale for Dosing ..................................................................................................... 25 
5.3 
Randomization and Blinding ......................................................................................... 25 
5.4 
Breaking the Blind ........................................................................................................ 25 
5.5 
Drug Supplies ................................................................................................................ 26 
5.5.1  Formulation and Packaging ............................................................................... 26 
5.5.2  Study Drug Preparation and Dispensing ........................................................... 26 
5.5.3  Study Drug Administration ............................................................................... 26 


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5.5.4  Treatment Compliance ...................................................................................... 26 
5.5.5  Storage and Accountability ............................................................................... 26 
5.6 
Prior and Concomitant Medications and/or Procedures ................................................ 27 
5.6.1  Excluded Medications ....................................................................................... 27 
5.6.2  Documentation of Prior and Concomitant Medication Use .............................. 27 
6  Study Procedures .................................................................................................................... 28 
7  Endpoints ................................................................................................................................ 29 
7.1 
Symptom Assessments .................................................................................................. 29 
7.1.1  Global Impression Visual Analog Scale ........................................................... 29 
7.1.2  Clinical Global Impression-Impairment Severity and -Improvement Scales ... 29 
7.1.3  Alcohol Toxicity Symptom Scale ..................................................................... 29 
7.2 
Sign Assessments .......................................................................................................... 30 
7.2.1  Objective Flushing and Ocular Redness ........................................................... 30 
7.2.2  Proprioception Tests .......................................................................................... 30 
7.3 
Pharmacodynamic Assessments .................................................................................... 30 
8  Safety Assessments ................................................................................................................. 31 
8.1 
Adverse Events .............................................................................................................. 31 
8.1.1  Adverse (Drug) Reaction .................................................................................. 32 
8.1.2  Unexpected Adverse Drug Reaction ................................................................. 32 
8.1.3  Assessment of Adverse Events by the Investigator .......................................... 32 
8.1.4  Adverse Events of Special Interest .................................................................... 33 
8.1.5  Study Stopping Rules ........................................................................................ 33 
8.1.6  Special Safety Considerations ........................................................................... 34 
8.2 
Serious Adverse Events ................................................................................................. 34 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators ................................ 35 
8.4 
Pregnancy Reporting ..................................................................................................... 35 
8.5 
Expedited Reporting ...................................................................................................... 36 
8.6 
Special Situation Reports .............................................................................................. 36 
8.7 
Clinical Laboratory Evaluations .................................................................................... 37 
8.8 
Vital Signs ..................................................................................................................... 38 
8.9 
Electrocardiograms ........................................................................................................ 38 
8.10  Physical Examinations .................................................................................................. 38 


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9  Statistics .................................................................................................................................. 39 
9.1 
Analysis Populations ..................................................................................................... 39 
9.2 
Statistical Methods ........................................................................................................ 39 
9.2.1  Analysis of Efficacy .......................................................................................... 39 
9.2.2  Analysis of Demographic and Baseline Characteristics ................................... 39 
9.2.3  Analysis of Safety ............................................................................................. 39 
9.2.4  Interim Analysis ................................................................................................ 39 
9.2.5  Sample Size Determination ............................................................................... 39 
10  Data Management and Record Keeping ................................................................................. 40 
10.1  Data Management ......................................................................................................... 40 
10.1.1  Data Handling ................................................................................................... 40 
10.1.2  Computer Systems ............................................................................................. 40 
10.1.3  Data Entry ......................................................................................................... 40 
10.1.4  Medical Information Coding ............................................................................. 40 
10.1.5  Data Validation ................................................................................................. 40 
10.2  Record Keeping ............................................................................................................. 40 
10.3  End of Study .................................................................................................................. 41 
11  Investigator Requirements and Quality Control ..................................................................... 42 
11.1  Ethical Conduct of the Study ........................................................................................ 42 
11.2  Institutional Review Board ............................................................................................ 42 
11.3  Informed Consent .......................................................................................................... 42 
11.4  Study Monitoring Requirements ................................................................................... 42 
11.5  Disclosure of Data ......................................................................................................... 43 
11.6  Retention of Records ..................................................................................................... 43 
11.7  Publication Policy ......................................................................................................... 43 
11.8  Financial Disclosure ...................................................................................................... 44 
12  Study Administrative Information .......................................................................................... 45 
12.1  Protocol Amendments ................................................................................................... 45 
13  References ............................................................................................................................... 46 
Appendix A: Schedule of Procedures ........................................................................................... 47 
Appendix B: Clinical Laboratory Analytes .................................................................................. 50 
Appendix C: Symptom Assessment Scales .................................................................................. 52 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS  
Abbreviation 
Definition 
ADH 
Alcohol dehydrogenase 
AE 
Adverse event 
ALDH 
Aldehyde dehydrogenase 
AUC 
Area under the concentration-time curve 
BAC 
Blood alcohol concentration 
BID 
Twice daily 
CFR 
Code of Federal Regulations 
CGI 
Clinical Global Impression 
Cmax 
Maximum plasma concentration 
COVID-19 
Coronavirus disease 2019 
CRA 
Clinical Research Associate 
CTCAE 
Common Terminology Criteria for Adverse Events 
DNA 
Deoxyribonucleic acid 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EIU 
Exposure In Utero 
FCBP 
Female of childbearing potential 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
HIV 
Human immunodeficiency virus 
HNE 
Hydroxynonenal 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IL 
Interleukin 
IRB 
Institutional Review Board 
MAA 
Malondialdehyde-acetaldehyde adduct 
MDA 
Malondialdehyde 
NAD 
Nicotinamide adenine dinucleotide 
NADH 
Nicotinamide adenine dinucleotide + hydrogen 
NASH 
Nonalcoholic steatohepatitis 
PD 
Pharmacodynamic(s) 
PK 
Pharmacokinetic(s) 
RASP 
Reactive aldehyde species 
RNA 
Ribonucleic acid 
ROS 
Reactive oxygen species 


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Abbreviation 
Definition 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus-2 
SUSAR 
Suspected unexpected serious adverse reaction 
Th 
T-helper 


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1 
INTRODUCTION AND BACKGROUND INFORMATION  
Aldeyra Therapeutics, Inc. has developed ADX-629, a proprietary new chemical entity for the 
treatment of systemic immune-mediated and inflammatory diseases that are believed to be caused 
or exacerbated by elevated concentrations of reactive aldehyde species (RASP). ADX-629 is a 
small molecule formulated for oral administration that binds rapidly and irreversibly to RASP such 
as hydroxynonenal (HNE) and malondialdehyde (MDA), thereby preventing RASP-mediated 
inflammation and other toxicities. 
1.1 
Background 
Ethanol, commonly referred to as alcohol, is a psychoactive substance with dependence-producing 
properties that has been widely used in many cultures for centuries.1 The harmful use of alcohol 
causes large disease, social, and economic burdens in societies. Alcohol consumption is a causal 
factor in more than 200 disease and injury conditions.1 Drinking alcohol is associated with a risk 
of developing health problems such as mental and behavioral disorders, including alcohol 
dependence; major noncommunicable diseases such as liver cirrhosis; some cancers; and 
cardiovascular diseases, as well as injuries resulting from violence and road clashes and collisions.1 
Furthermore, patients with nonalcoholic steatohepatitis (NASH) can have elevated levels of blood 
alcohol and proteobacteria, which produce alcohol. The understanding of the drug-alcohol 
interaction could help elucidate the mechanism of action of ADX-629 in NASH patients.  
The major enzyme systems responsible for the oxidation of ethanol are the alcohol dehydrogenase 
(ADH), and to a lesser extent, the cytochrome P450-dependent ethanol-oxidizing systems.2 These 
routes of ethanol metabolism result in the formation of acetaldehyde.2,3 Ethanol is metabolized in 
the liver by ADH to produce acetaldehyde, which is then further converted to acetate by aldehyde 
dehydrogenase (ALDH).2,3 The ADH and ALDH reactions lead to an accumulation of 
nicotinamide adenine dinucleotide  hydrogen (NADH), and the consequent reduction of the 
nicotinamide adenine dinucleotide (NAD+)/NADH ratio has a significant effect on important 
biochemical pathways, such as glycolysis, the citric acid cycle, fatty acid oxidation, and 
gluconeogenesis.3 NADH is mainly reoxidized to NAD+ by the mitochondrial electron transfer 
chain.4,5 During this electron transfer to oxygen, reactive oxygen species (ROS) are formed.4 A 
small portion of these ROS can generate toxic effects through lipid peroxidation, enzyme 
inactivation, DNA mutations, and destruction of cell membranes.6,7,8 Lipid peroxidation is the most 
important reaction involved in certain types of alcohol-induced damage, such as liver damage 
through the formation of RASP.9,10 
Through covalent binding to amino and thiol groups on receptors and kinases, RASP, such as HNE 
and MDA, potentiate upstream pro-inflammatory signaling cascades that involve the nuclear factor 
kappa-light-chain-enhancer of activated B cells, inflammasomes, scavenger receptor A, and other 
mediators.11,12,13,14 Elevations in RASP concentrations, particularly HNE and MDA, have been 
described in a variety of inflammatory diseases.  
ADX-629 acts as a RASP-sequestering agent by irreversibly binding to aldehydes and thereby 
preventing RASP-mediated inflammation and other toxicities. ADX-629 forms these adducts with 
RASP on a 1:1 stoichiometric basis. Thus, target concentrations of ADX-629 approximate levels 
of MDA. 


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1.1.1 
Nonclinical Studies of ADX-629 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.1.2 
Clinical Studies of ADX-629 
The potential benefit of RASP inhibition in immune-mediated and inflammatory diseases has been 
demonstrated by the first-in-class RASP inhibitor reproxalap (ADX-102), a structural homolog of 
ADX-629, which has shown to be beneficial in treating ocular inflammation, including dry eye 
disease and allergic conjunctivitis, across numerous Phase 2 and Phase 3 clinical trials, and is 
currently in Phase 3 clinical testing. 
In addition to nonclinical safety studies, clinical development of ADX-629 in inflammatory 
disease is supported by safety testing in healthy human volunteers in single and multiple ascending 
dose (10-day), placebo-controlled Phase 1 trials. Overall, ADX-629 was found to be safe and 
tolerable at the doses explored, including the maximum dose of 600 mg twice daily (BID). The 
adverse event (AE) profile of ADX-629 was favorable compared to placebo. A total of 
6 (9.4%) subjects who received ADX-629 had treatment-emergent AEs compared to 
4 (19.1%) subjects who received placebo. None of the subjects required interruption or 
discontinuation of study drug. 
Although pharmacokinetic (PK) variability was observed, a linear correlation was evident in 
maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) as dose 
increased. The half-life was consistent across cohorts and days, with mean values in multiple day 
exposures ranging between 3.49 to 6.83 hours. Little to no accumulation of the drug was observed 


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across cohorts. At the top dose (600 mg BID), a Cmax of 1750 ng/mL (approximately 8.7 μM) and 
an AUC from time 0 to 12 hours of 6.260 h*ng/mL averaged at Day 1 and Day 10 were consistent 
with an adequate molar ratio to achieve stoichiometric efficacy against elevated RASP. A decrease 
in free MDA levels was observed in the plasma of healthy volunteers over 10 days of dosing with 
ADX-629 600 mg BID that was statistically greater than that of subjects treated with placebo. 
Following ingestion of a high-fat meal on Day 10 of dosing with 600 mg BID or placebo, levels 
of free fatty acids were statistically lower and levels of high-density lipoproteins were statistically 
higher in ADX-629-treated subjects than in placebo-treated subjects, potentially representing 
additional anti-inflammatory activity of ADX-629. 
Additionally, ADX-629 is currently being evaluated in a Phase 2a clinical trial for the treatment 
of inflammation associated with coronavirus disease 2019 (COVID-19), asthma, and psoriasis. 
1.2 
Rationale 
This Phase 1b, randomized, double-blind study will assess the interaction between ADX-629 and 
ethanol while exploring the safety, tolerability, and activity of ADX-629 in subjects with elevated 
ethanol levels. 
Scientific evidence suggests that administration of ADX-629 may mitigate the effects of 
acetaldehyde and other toxic metabolites of ethanol in subjects with acute ethanol toxicity. 
ADX-629 may mitigate the inflammatory response sufficiently to lower levels of RASP and 
potentially improve outcomes of subjects. 
1.3 
Risk/Benefit 
The ADX-629-ET-001 study will assess the interaction between ADX-629 and ethanol while 
exploring the safety, tolerability, and activity of ADX-629 in subjects with elevated ethanol levels. 
The safety of the clinical dosing regimen in this study is supported by a Phase 1 study in healthy 
volunteers and a number of nonclinical toxicology and PK studies in which no serious safety 
concerns or treatment-related AEs were noted at the proposed dose after 10 days of BID 
administration. 
Refer to the Investigator’s Brochure for additional information. 


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2 
STUDY OBJECTIVE 
2.1 
Primary Objective 
The primary objective is to assess the interaction between ADX-629 and ethanol while exploring 
the safety, tolerability, and activity of ADX-629 in subjects with elevated ethanol levels. 


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3 
STUDY DESCRIPTION  
3.1 
Summary of Study Design 
ADX-629-ET-001 is a Phase 1b, single-center, double-blind, placebo-controlled, randomized, 
crossover study to assess the interaction between ADX-629 and ethanol while exploring the safety, 
tolerability, and activity of ADX-629 in subjects with elevated ethanol levels. Approximately 
30 subjects are expected to be enrolled in the study.  
This study will utilize a 2-sequence, 2-period, 2-way crossover design. Subjects will be 
randomized to 1 of 2 treatment sequences (AB or BA) on Day 1 of Treatment Period 1.  
 Treatment A: 3 oral doses of ADX-629 600 mg (2 × 300 mg) oral tablets; and 
 Treatment B: 3 oral doses of matching placebo. 
Study procedures will be completed during the following periods: 
 A Screening Period (Day -28 to -2); 
 Two 3-day inpatient periods (Treatment Periods 1 and 2) (from Check-In through completion 
of treatment period), each consisting of the following: 
o Check-In: Subjects will be admitted to the study site on the day prior to dosing in each 
treatment period. Baseline symptom and sign assessments (except for the Clinical Global 
Impression [CGI]-Improvement Scale) will be completed, and subjects will then be housed 
overnight where they will be required to adhere to a standardized high-fat, high-sucrose 
diet; 
Note: Subjects will be reminded at the beginning of each treatment period that this study 
is placebo-controlled. The placebo-control reminder text will be read as follows: “You are 
participating in a placebo-controlled study, which means that you will not know if you are 
taking a sugar pill or a drug pill. It is important that you try not to decide whether you have 
taken a sugar pill or a drug pill. Any questions that you answer about how you are feeling 
should not be influenced by whether or not you believe you have taken a sugar pill or a 
drug pill. Please answer questions about how you are feeling as if you had not taken any 
pill at all.” 
o Day 1: 1 dose of study drug will be administered at approximately 4:30 pm followed by 
standardized ethanol consumption as outlined in the manual, and then 1 dose of study drug 
will be administered at approximately 7 pm followed by continued standardized ethanol 
consumption to reach a target blood alcohol concentration (BAC) of 0.14 g/100 mL, 
measured via breathalyzer. For more details on the breathalyzer measurements, refer to the 
Study Procedures Manual. Symptom and sign assessments (with the exception of the 
CGI-Improvement Scale) will be evaluated and should be completed as soon as practical 
after target BAC is reached. Study procedures will be reviewed for randomized subjects, 
and, based on the emerging data, the standardized ethanol solution and/or BAC testing 
methods may be modified as needed to ensure target BAC is reached within a 4-hour 
window for the remaining subjects; and 
Note: Subjects will be observed for safety during the treatment periods by study site 
personnel who will be present to assist subjects at all times; there will be a minimum 


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requirement of at least 2 study site personnel to assist subjects during their assessments. 
Safety measures will be in place to prevent falling. 
Note: Ethanol will be administered in a standardized oral solution. For more details on the 
consumption guidelines, refer to the Study Procedures Manual. 
o Day 2: 1 dose of study drug will be administered at approximately 8 am, and symptom and 
sign assessments (including the CGI-Improvement Scale) will be completed at 
approximately 7 am, 10 am, and 1 pm. Subjects will be discharged from the study site after 
completion of study procedures (approximately 12 hours after the last dose of study drug). 
Prior to discharge, vital signs will be measured. Subjects will have to achieve a BAC of 
0.00 g/100 mL as measured by a breathalyzer before discharge. 
 A follow-up telephone call will occur 3 days (1 day) after completion of Treatment Period 2. 
For subjects who are withdrawn from the study prior to completion, study procedures will be 
performed at an Early Termination Visit. 
There will be at least a 14-day washout period between the last dose of study drug in Treatment 
Period 1 and the first dose of study drug in Treatment Period 2. Subjects will need to refrain from 
drinking alcohol during the washout period.  
An individual subject’s participation in the study is estimated to be approximately 41 days. 
3.2 
Study Indication 
This Phase 1b study will assess the interaction between ADX-629 and ethanol while exploring the 
safety, tolerability, and activity of ADX-629 in subjects with elevated ethanol levels. 


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4 
SELECTION AND WITHDRAWAL OF SUBJECTS  
4.1 
Inclusion Criteria 
Subjects meeting all of the following criteria will be considered eligible for the study: 
 Male or female subjects between the ages of 21 and 65 years, inclusive, at Screening; 
 
 
 
 Subjects with the ability to obtain transportation to and from the study site; 
 Subjects with a history of alcohol-related symptoms or negative symptomatology following 
the consumption of 4 alcoholic beverages; 
Note: Alcohol-related symptoms may include any of the following: headache, flushing, 
fatigue, diarrhea, nausea, dizziness, confusion/disorientation, or nystagmus. 
 
 
 
 Subjects who agree to avoid use of prescription or over-the-counter medications, including 
topicals, herbal supplements, dietary supplements (excluding fish oil), or nutraceuticals within 
14 days prior to Screening until the end of the study; 
Note: Subjects must avoid oral contraceptives from within 7 days prior to Screening until the 
end of the study and immunomodulators (eg, corticosteroids, cytokine inhibitors, and Janus 
kinase inhibitors) from within 60 days prior to Screening until the end of the study. 
 Subjects (all females of childbearing potential [FCBPs] and males with a female partner of 
childbearing potential) who agree to use an effective form of contraception (nonhormonal or 
barrier method) during the study and for 7 days after the last dose of study drug; 
Note: An FCBP is defined as any female, regardless of sexual orientation, who has not 
undergone a hysterectomy, bilateral oophorectomy, salpingectomy, or bilateral tubal ligation 
or has not been naturally postmenopausal for at least 12 consecutive months (ie, has had 
menses at any time in the preceding 12 consecutive months) with a negative 
follicle-stimulating hormone (FSH) test. An FSH test will be performed at Screening in all 
naturally postmenopausal women to confirm menopausal status. 
Note: Sperm donation is also prohibited during the study and for 90 days after the last dose of 
study drug. 
 Subjects who are willing to consume the standardized alcohol preparation; 
 
 
 
 
 
 Subjects who agree to abstain from consumption of non-study alcohol during the study. 


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4.2 
Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from the study: 
 
 
 
 
 Subjects with abnormal laboratory values of clinical significance, at the discretion of the 
Investigator, at Screening; 
Note: 1 repeat of laboratory assessments is allowed to confirm abnormal values. 
 
 
 
 
 Subjects with a history of or active: 
o Reactive airway disease; 
o Diabetes; 
o Kidney or bladder stones; 
o Kidney disease (including past or current dialysis requirement); 
o Liver disease; 
o Stomach ulcer; 
o Organ transplant; 
o Gastric bypass; or 
o Any other medical/surgical condition of clinical significance, at the discretion of the 
Investigator. 
 Subjects with nicotine product use within 14 days prior to Screening until the end of the study; 
 Subjects with any history of or current alcohol or other substance use disorder diagnosed 
according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition; 
 Subjects with a positive urine drug screen or breath alcohol test at Screening or Check-In (both 
treatment periods);  
 
 
 
 Subjects who are currently pregnant or lactating or plan to become pregnant during the study; 
Note: A serum pregnancy test will be performed in all FCBPs at Screening and a urine 
pregnancy test will be performed at Check-In (both treatment periods). 
 Subjects who are positive for HIV antibody, hepatitis C virus antibody, hepatitis B virus 
surface antigen, or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA; 


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 Subjects who have participated in any other investigational study within the past 30 days or 
within 5 half-lives of the investigational therapy, whichever is longer, at Screening;  
 Subjects currently taking or who cannot abstain from corticosteroids, cytokine inhibitors, Janus 
kinase inhibitors, and/or nonsteroidal anti-inflammatory drugs; or 
 Subjects currently taking or who cannot abstain from medications that can cause a 
disulfiram-like reaction (eg, metronidazole) or who have taken such medications within the 
past 30 days at Screening. 
4.3 
Withdrawal Criteria 
Participation of a subject in this study may be discontinued for any of the following reasons: 
 Sponsor decision;  
 The subject withdraws consent or requests discontinuation from the study for any reason; 
 Occurrence of any medical condition or circumstance that exposes the subject to substantial 
risk and/or does not allow the subject to adhere to the requirements of the protocol; 
 Any serious AE (SAE), clinically significant AE, severe laboratory abnormality, intercurrent 
illness, or other medical condition that indicates to the Investigator that continued participation 
is not in the best interest of the subject; 
 Pregnancy; 
 Subject requirement of prohibited concomitant medication; 
 Subject failure to comply with protocol requirements or study-related procedures; or 
 Termination of the study by the Sponsor or the regulatory authority. 
Unless a subject withdraws consent for further follow-up, subjects who discontinue study drug 
(ADX-629 or placebo) will continue in the study for acquisition of safety assessments through the 
follow-up telephone call. If a subject withdraws prematurely from the study due to the above 
criteria or any other reason, study staff should make every effort to complete the full panel of 
assessments scheduled for the Early Termination Visit. The reason for subject withdrawal must be 
documented in the electronic case report form (eCRF). 
In the case of subjects lost to follow-up, attempts to contact the subject must be made and 
documented in the subject’s medical records. 
Withdrawn subjects may be replaced at the discretion of the Sponsor.  
Additional subjects will be screened as reserve subjects. Reserve subjects who are eligible for 
enrollment will also be admitted to the study site to ensure enough eligible subjects are available 
to fill the treatment sequence. Subjects who fulfill the eligibility criteria but are not randomized 
may either remain at the study site for participation on a subsequent dosing date or they may be 
discharged and return for a future dosing date. It is not required that the Screening procedures be 
repeated provided, the subject remains within the screening window. Check-In procedures do not 
need to be repeated if the subject remains confined to the study site and protocol restrictions are 
monitored and followed. If the subject is discharged and returns, Check-In procedures will be 
repeated. Reserve subjects who remain eligible but fall outside of the screening window will be 
allowed to rescreen. 


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4.4 
Rescreening 
Subjects who have met the eligibility criteria, but are out of the screening window before admission 
to the study site, are allowed to rescreen for the study.  
Subjects who have screen failed for any reason are permitted to rescreen once, following 
consultation with the Medical Monitor. 


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5 
STUDY TREATMENTS 
5.1 
Treatment Groups 
All subjects will receive 3 doses of ADX-629 600 mg (2 × 300 mg) oral tablets and 3 doses of 
matching placebo. The study drug will be administered twice on Day 1, the first dose prior to the 
commencement of the standardized ethanol consumption, and once on the day following ethanol 
consumption (Day 2).  
5.2 
Rationale for Dosing 
 
 
 
 
 
5.3 
Randomization and Blinding 
Subjects will be randomized to 1 of 2 treatment sequences (AB or BA) on Day 1 of Treatment 
Period 1.  
 Treatment A: 3 oral doses of ADX-629 600 mg (2 × 300 mg) oral tablets; and 
 Treatment B: 3 oral doses of matching placebo. 
Subjects, Investigators, and study site personnel (including the Sponsor/designee) involved in the 
administration and assessment of the study drug will be blinded to the subject treatment 
assignments throughout the study. 
5.4 
Breaking the Blind 
The Investigator is responsible for the medical care of subjects during the study. In an emergency, 
when knowledge of the subject’s treatment assignment is essential for the clinical management or 
welfare of the subject, the Investigator can unblind the treatment assignment. It is encouraged that 
the Investigator contact the Medical Monitor (or designee) before proceeding with the unblinding 
process. Unblinding should only occur for the subject in question if it is critical for treatment 
decision making by the Investigator for the well-being of the subject. 
Prior to unblinding the subject’s treatment assignment, the Investigator should assess the 
relationship of the AE to study drug (yes or no). If unblinding is warranted, the Investigator must 
then follow the appropriate procedures to unblind an individual subject’s treatment assignment.  
Generally, the blind should only be broken for events that are considered to be serious, unexpected, 
and causally related to the study treatments, or as requested by local regulatory authorities.  
If the study blind is broken, the Investigator must detail the date and reason for unblinding in the 
subject’s records. The Investigator must also notify the Sponsor (and Institutional Review Board 
(IRB) if applicable), if this has not already been done, that the study blind has been broken. If the 
blind is broken due to an AE, the AE form must be completed and reported to the Sponsor (see 
Section 8.6). 


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5.5 
Drug Supplies 
5.5.1 
Formulation and Packaging 
Aldeyra Therapeutics, Inc. will supply sufficient quantities of study drug (ADX-629 and matching 
placebo) to allow for completion of the study. The lot numbers will be recorded in the final Clinical 
Study Report. 
ADX-629 and matching placebo will each be available as tablets for oral administration. Study 
drug will be packaged in a kit with 2 bottles, each bottle containing thirty 300 mg tablets. 
5.5.2 
Study Drug Preparation and Dispensing 
 
5.5.3 
Study Drug Administration 
For both treatment periods, ADX-629 600 mg (2 × 300 mg) oral tablets and matching placebo 
tablets will be administered twice on Day 1, the first dose prior to the commencement of the 
standardized ethanol consumption, and once on the day following ethanol consumption (Day 2). 
Each subject will receive 3 doses of ADX-629. No dose interruptions or reductions will be 
permitted. 
5.5.4 
Treatment Compliance 
To ensure treatment compliance, all doses will be administered under the supervision of study site 
personnel. A mouth and hand check will be carried out to ensure the tablets are swallowed. 
The Investigator is responsible for maintaining specific subject records to document all study drug 
dispensed and administered. 
5.5.5 
Storage and Accountability 
The pharmacist (or designee) will acknowledge receipt of all shipments of study drug and maintain 
an inventory. Study drug must be kept in a locked area with restricted access and stored and 
handled in accordance with the manufacturer's instructions. The pharmacist (or designee) will also 
keep accurate records of the quantities of study drug dispensed and used by each subject. The 
Clinical Research Associate (CRA) will periodically check the supply of study drug held by the 
pharmacist in a blinded fashion to verify accountability of all study drug used. 
At the conclusion of the study, all unused study drug will be returned to the Sponsor unless other 
arrangements have been approved by the Sponsor. The Sponsor will verify that a final report of 
study drug accountability to the unit dose level is prepared and maintained in the Investigator 
clinical study file. 
 
 
 


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5.6 
Prior and Concomitant Medications and/or Procedures 
5.6.1 
Excluded Medications 
 
 
 
 
 
 
 
 
 
 
 
 
5.6.2 
Documentation of Prior and Concomitant Medication Use 
Any medications administered 30 days prior to the first dose of study drug through Day 2 of 
Treatment Period 2 must be recorded. 


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6 
STUDY PROCEDURES 
Study staff will always be present to assist and ensure subject safety. There will be a minimum of 
2 staff members to assist subjects during assessments, and a security officer will be in the unit 
supervising subjects while intoxicated. If a subject becomes a danger to themselves or others, they 
will be isolated and may be physically restrained using soft hospital-approved restraints. 
During the study, subjects will stay in private rooms and not be sharing rooms. Some procedures 
(ie, digital photography) will occur outside their room, and subjects will be accompanied by staff 
throughout the protocol assessments. Throughout the study, subjects will be instructed to remain 
in their personal space and continuously supervised by multiple staff. 
Staff will always be present to monitor, assist, and ensure subject safety. There will be a minimum 
of 2 staff members to assist subjects during assessments. Subjects will be sequestered to their 
private rooms while intoxicated. Staff will be available to escort subjects to the restroom. Each 
restroom is equipped with an alarm. Arrangements could also be made for a bedside commode and 
urinals as needed. 
Study procedures will follow the Schedule of Procedures (Appendix A). 


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7 
ENDPOINTS 
The study is not formally powered as all endpoints are exploratory in nature. 
The primary exploratory efficacy endpoints include the following: 
 Assessment of symptoms using the Global Impression Visual Analog Scale, CGI-Impairment 
Severity Scale, CGI-Improvement Scale, and the Alcohol Toxicity Symptom Scale; 
 Assessment of signs, determined by evaluation of the following: 
o Objective flushing and ocular redness scales (via digital photography); and 
o Proprioception tests (Romberg Test [time of up to 60 seconds], One Leg Stand Test [time 
of up to 60 seconds], Straight-Line Heel-to-Toe Test [up to 100 steps]). 
 Assessment of ADX-629 activity, determined by evaluation of the following PD markers, for 
both treatment periods, on Day 1 pre-dose, on Day 1 one hour after the target BAC is achieved, 
and on Day 2 one hour after the last dose of study drug: 
o HNE, acetaldehyde, malondialdehyde-acetaldehyde adduct (MAA), and MDA plasma 
concentrations; and 
o Plasma cytokine concentrations including, but not limited to, interferon gamma, IL-1b, 
IL-10, IL-12, and IL-17. 
7.1 
Symptom Assessments 
7.1.1 
Global Impression Visual Analog Scale 
For both treatment periods, subjects will be asked to assess the extent of their symptoms at the 
timepoints indicated in the Schedule of Procedures (Appendix A) utilizing the Global Impression 
Visual Analog Scale (Appendix C). The extent of symptoms will be assessed on a 100-point scale 
from no symptoms to maximal symptoms.  
7.1.2 
Clinical Global Impression-Impairment Severity and -Improvement Scales 
For both treatment periods, subjects will be asked to rate their overall severity of impairment and 
improvement in symptoms at the timepoints indicated in the Schedule of Procedures (Appendix A) 
utilizing the CGI-Impairment Severity and CGI-Improvement Scales (Appendix C).  
Overall severity of impairment will be assessed on a 7-point scale from no impairment to very 
severe impairment.  
For both treatment periods on Day 2, overall improvement of symptoms (relative to symptoms 
upon waking on Day 2) will be assessed on a 7-point scale from very much worse to very much 
improved. The CGI-Improvement Scale will only be administered on Day 2 at approximately 
7 am, 10 am, and 1 pm. 
7.1.3 
Alcohol Toxicity Symptom Scale 
The subjects will be asked to score their symptoms at the timepoints indicated in the Schedule of 
Procedures (Appendix A) utilizing the Alcohol Toxicity Symptom Scale (Appendix C). This scale 
will include assessment of hydration status, fatigue, headache, and nausea including inquiries 
about vomiting, muscle weakness, ability to concentrate, light and sound sensitivity, sweating, 


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trembling/shaking, and mood such as anxiety and/or depression. For the 0 to 10 scale in the 
Alcohol Toxicity score, subjects will be instructed that a “10” implies that the subject would have 
to call off from work and/or be unable to perform normal activities until recovered, due to that 
specific symptom. A “5” implies that the subject could perform normal activities, such as work, 
but with a decreased performance level. A “0” implies that there would be no impact on normal 
activities at all. For the thirst/dehydration and sweating category, subjects will rank their symptom 
on a scale of 0 to 10 based on prior, subjective experience. 
The vomiting category within the Alcohol Toxicity Symptom Scale is meant to measure the 
secondary effects of ethanol toxicity (ie, from acetaldehyde) as opposed to effects related to 
euphoria or central nervous system depression. Vomiting will be evaluated separately with 
individual AEs. A positive vomiting score will be documented if vomiting has occurred 8 to 
12 hours after BAC is met. Vomiting observed 0 to 8 hours after BAC is met will not be included 
in the toxicity reporting. 
7.2 
Sign Assessments 
7.2.1 
Objective Flushing and Ocular Redness 
Subjects will be evaluated for signs of objective flushing and ocular redness via digital 
photography at the timepoints indicated in the Schedule of Procedures (Appendix A). 
7.2.2 
Proprioception Tests 
Subjects will be evaluated for proprioception using the Romberg Test, One Leg Stand Test, and 
Straight-Line Heel-to-Toe Test at the timepoints indicated in the Schedule of Procedures 
(Appendix A). 
The Romberg Test will be conducted in a standing position with the subject’s feet together, arms 
by the side, and eyes closed. Subjects will be evaluated to determine how long they can stand 
without movement, (eg, any part of body movement, including eyes opening). Slight swaying is 
allowed. The length of time the subject is able to stand without movement will be recorded. 
The One Leg Stand Test will be conducted in a standing position with one of the subject’s legs 
raised slightly off the ground. The length of time the subject is able to stand in this position will 
be recorded. 
The Straight-Line Heel-to-Toe Test will be conducted with the subject walking heel-to-toe on a 
demarcated floor that will include a walking line and an “out-of-bounds” area marked 3 to 6 inches 
outside of the walking line. The number of steps the subject is able to take without stepping 
“out-of-bounds” will be recorded. 
7.3 
Pharmacodynamic Assessments 
Blood samples for PD markers, such as plasma HNE, plasma acetaldehyde, plasma MAA, plasma 
MDA, and plasma cytokine concentrations (including, but not limited to, interferon gamma, IL-1b, 
IL-10, IL-12, and IL-17) will be collected for both treatment periods on Day 1 pre-dose, on Day 1 
one hour after the target BAC is achieved, and on Day 2 one hour after the last dose of study drug. 


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8 
SAFETY ASSESSMENTS 
The primary safety endpoint is the safety and tolerability of ADX-629, determined by evaluation 
of the following: 
 AEs; 
 Physical examinations; 
 Vital signs (blood pressure, heart rate, respiratory rate, temperature, and oxygen saturation); 
 12-lead electrocardiograms (ECGs); 
 BAC; 
 Clinical laboratory assessments (including chemistry, hematology, and urinalysis); and 
 Lipid panel evaluations. 
8.1 
Adverse Events 
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and/or unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of an 
investigational medicinal product, whether or not related to the investigational medicinal product. 
All AEs, including observed or volunteered problems, complaints, or symptoms, are to be recorded 
on the appropriate eCRF. 
AEs, which include clinical laboratory test variables, will be monitored and documented from the 
time of informed consent until study participation is complete. SAEs occurring from the time of 
informed consent until 30 days following the last administration of study drug will be monitored 
and documented. Subjects should be instructed to report any AE that they experience to the 
Investigator, whether or not they think the event is due to study treatment. Beginning at Screening, 
Investigators should make an assessment for AEs at each visit and record the event on the 
appropriate AE eCRF. 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF. However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate AE on the eCRF. Additionally, 
the condition that led to a medical or surgical procedure (eg, surgery, endoscopy, tooth extraction, 
or transfusion) should be recorded as an AE, not the procedure itself.  
Any medical condition already present at Screening should be recorded as medical history and not 
be reported as an AE unless the medical condition or signs or symptoms present at baseline changes 
in severity, frequency, or seriousness at any time during the study. In this case, it should be reported 
as an AE. 
Clinically significant abnormal laboratory or other examination (eg, ECG) findings that are 
detected during the study or are present at Screening and significantly worsen during the study 
should be reported as AEs, as described below. The Investigator will exercise his or her medical 
and scientific judgment in deciding whether an abnormal laboratory finding or other abnormal 
assessment is clinically significant. Clinically significant abnormal laboratory values occurring 


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during the clinical study will be followed until repeat tests return to normal, stabilize, or are no 
longer clinically significant. Abnormal test results that are determined to be an error should not be 
reported as an AE. Laboratory abnormalities or other abnormal clinical findings (eg, ECG 
abnormalities) should be reported as an AE if any of the following are applicable: 
 If an intervention is required as a result of the abnormality; 
 If action taken with the study drug is required as a result of the abnormality; or 
 Based on the clinical judgment of the Investigator. 
8.1.1 
Adverse (Drug) Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered an adverse drug reaction. “Responses” to a medicinal product means that a causal 
relationship between a medicinal product and an AE is at least a reasonable possibility, ie the 
relationship cannot be ruled out. 
8.1.2 
Unexpected Adverse Drug Reaction 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity of 
which is not consistent with the applicable product information.  
8.1.3 
Assessment of Adverse Events by the Investigator 
The Investigator will assess the severity (intensity) of each AE as mild, moderate, or severe, and 
will also categorize each AE as to its potential relationship to study drug using the categories of 
yes or no. 
Assessment of severity: 
The severity of all AEs should be graded according to the latest version of Common Terminology 
Criteria for Adverse Events (CTCAE). For those AE terms not listed in the CTCAE, the following 
grading system should be used: 
 CTCAE Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated; 
 CTCAE Grade 2: Moderate; minimal local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living; 
 CTCAE Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
activities of daily living; 
 CTCAE Grade 4: Life-threatening consequences; urgent intervention indicated; and 
 CTCAE Grade 5: Death related to the AE. 


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Causality assessment: 
The relationship of an AE to the administration of the study drug is to be assessed according to the 
following definitions: 
No (unrelated, not related, unlikely to be related) – The time course between the administration of 
study drug and the occurrence or worsening of the AE rules out a causal relationship and another 
cause (concomitant drugs, therapies, complications, etc) is suspected. 
Yes (possibly, probably, or definitely related) – The time course between the administration of 
study drug and the occurrence or worsening of the AE is consistent with a causal relationship and 
no other cause (concomitant drugs, therapies, complications, etc) can be identified. 
The definition implies a reasonable possibility of a causal relationship between the event and the 
study drug. This means that there are facts (evidence) or arguments to suggest a causal relationship. 
The following factors should also be considered: 
 The temporal sequence from study drug administration; 
The event should occur after the study drug is given. The length of time from study drug 
exposure to event should be evaluated in the clinical context of the event. 
 Underlying, concomitant, intercurrent diseases; 
Each report should be evaluated in the context of the natural history and course of the disease 
being treated and any other disease the subject may have. 
 Concomitant drug; 
The other drugs the subject is taking or the treatment the subject receives should be examined 
to determine whether any of them might be recognized to cause the event in question. 
 Known response pattern for this class of study drug; 
Clinical and/or preclinical data may indicate whether a particular response is likely to be a 
class effect. 
 Exposure to physical and/or mental stresses; and 
The exposure to stress might induce adverse changes in the recipient and provide a logical and 
better explanation for the event. 
 The pharmacology and PK of the study drug; 
The known pharmacologic properties (absorption, distribution, metabolism, and excretion) of 
the study drug should be considered. 
8.1.4 
Adverse Events of Special Interest 
There are no AEs of special interest defined for this study. 
8.1.5 
Study Stopping Rules 
 
 
 


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8.1.6 
Special Safety Considerations 
Study staff will always be present to assist and ensure subject safety. There will be a minimum of 
2 staff members to assist subjects during assessments, and a security officer will be in the unit 
supervising subjects while intoxicated. If a subject becomes a danger to themselves or others, they 
will be isolated and may be physically restrained using soft hospital-approved restraints. 
During the study, subjects will stay in private rooms and not be sharing rooms. Some procedures 
(ie, digital photography) will occur outside their room, and subjects will be accompanied by staff 
throughout the protocol assessments. Throughout the study, subjects will be instructed to remain 
in their personal space and continuously supervised by multiple staff. 
Staff will always be present to monitor, assist, and ensure subject safety. There will be a minimum 
of 2 staff members to assist subjects during assessments. Subjects will be sequestered to their 
private rooms while intoxicated. Staff will be available to escort subjects to the restroom. Each 
restroom is equipped with an alarm. Arrangements could also be made for a bedside commode and 
urinals as needed. 
8.2 
Serious Adverse Events 
An AE or adverse reaction is considered serious if, in the view of either the Investigator or Sponsor, 
it results in any of the following outcomes: 
 Death; 
 A life-threatening AE; 
Note: An AE or adverse reaction is considered “life-threatening” if, in view of either the 
Investigator or Sponsor, its occurrence places the subject at immediate risk of death. It does 
not include an event that, had it occurred in a more severe form, might have caused death. 
 Requires hospitalization or prolongation of existing hospitalizations; 
Note: Any hospital admission with at least 1 overnight stay will be considered an inpatient 
hospitalization. An emergency room or urgent care visit without hospital admission will not 
be recorded as a SAE under this criterion, nor will hospitalization for a procedure scheduled 
or planned before signing of informed consent, or elective treatment of a pre-existing condition 
that did not worsen from baseline. However, unexpected complications and/or prolongation of 
hospitalization that occur during elective surgery should be recorded as AEs and assessed for 
seriousness. Admission to the hospital for social or situational reasons (ie, no place to stay, live 
too far away to come for hospital visits, respite care) will not be considered inpatient 
hospitalizations.  


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 A persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions; 
 A congenital anomaly/birth defect; or 
 An important medical event. 
Note: Important medical events that do not meet any of the above criteria may be considered 
an SAE when, based upon appropriate medical judgment, they may jeopardize the subject and 
may require medical or surgical intervention to prevent one of the outcomes listed above. 
Examples of such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalizations, or the development of drug dependency. 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators 
Initial reports: 
All SAEs occurring from the time of informed consent until 30 days following the last 
administration of study drug will be monitored and documented and must be reported to 
 
Clinical Safety within 24 hours of the knowledge of the occurrence. After the 30-day reporting 
window, any SAE that the Investigator considers related to study drug must be reported to 
 Clinical Safety or the Sponsor/designee. 
To report the SAE, complete the SAE form electronically in the electronic data capture (EDC) 
system for the study. When the form is completed, 
personnel will be notified 
electronically by the EDC system and will retrieve the form. If the event meets serious criteria and 
it is not possible to access the EDC system, send an email to 
 
 
 
. When the EDC system becomes 
available, the SAE information must be entered within 24 hours of the system becoming available. 
Follow-up reports: 
The Investigator must continue to follow the subject until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the subject 
dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
electronically in the EDC system for the study and submit any supporting documentation 
(eg, subject discharge summary or autopsy reports) to 
 Clinical Safety via fax or email. 
If it is not possible to access the EDC system, refer to the procedures outlined above for initial 
reporting of SAEs. 
8.4 
Pregnancy Reporting 
If a subject becomes pregnant during the study or within the safety follow-up period defined in the 
protocol, the Investigator is to stop dosing with study drug immediately and the subject should be 
withdrawn from the study. Early termination procedures should be implemented at that time.  
A pregnancy is not considered to be an AE or SAE; however, it must be reported to 
 
Clinical Safety within 24 hours of knowledge of the event. 
 Clinical Safety will then 


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provide the Investigator/site the Exposure In Utero (EIU) form for completion. The 
Investigator/site must complete the EIU form and fax/email it back to
 Clinical Safety.  
If the female partner of a male subject becomes pregnant while the subject is receiving study drug 
or within the safety follow-up period defined in the protocol, the Investigator should notify 
 Clinical Safety as described above.  
The pregnancy should be followed until the outcome of the pregnancy, whenever possible. Once 
the outcome of the pregnancy is known, the EIU form should be completed and faxed/emailed to 
 Clinical Safety. If the outcome of the pregnancy meets the criteria for immediate 
classification as an SAE (ie, postpartum complication, spontaneous abortion, stillbirth, neonatal 
death, or congenital anomaly), the Investigator should follow the procedures for reporting an SAE. 
8.5 
Expedited Reporting 
The Sponsor/designee will report all relevant information about suspected unexpected serious 
adverse reactions (SUSARs) that are fatal or life-threatening as soon as possible to the FDA and 
in any case no later than 7 days after knowledge by the Sponsor/designee of such a case. Relevant 
follow-up information will subsequently be communicated within an additional 8 days.  
All other SUSARs will be reported to the FDA as soon as possible but within a maximum of 
15 days of first knowledge by the Sponsor/designee.  
The Sponsor/designee will also report any additional expedited safety reports required in 
accordance with the timelines outlined in country-specific legislation.  
The Sponsor/designee will also inform all Investigators as required per local regulation. 
The requirements above refer to the requirements relating to study drug. 
8.6 
Special Situation Reports 
Special Situation Reports include reports of overdose, misuse, abuse, medication error, and reports 
of adverse reactions associated with product complaints. 
 Overdose: Refers to the administration of a quantity of a medicinal product given per 
administration or cumulatively (accidentally or intentionally), which is above the maximum 
recommended dose according to the protocol. Clinical judgement should always be applied. In 
cases of a discrepancy in the drug accountability, overdose will be established only when it is 
clear that the subject has taken additional dose(s) or the Investigator has reason to suspect that 
the subject has taken additional dose(s).  
 Misuse: Refers to situations where the medicinal product is intentionally and inappropriately 
used in a way that is not in accordance with the protocol instructions or local prescribing 
information and may be accompanied by harmful physical and/or psychological effects.  
 Abuse: Is defined as persistent or sporadic, intentional excessive use of a medicinal product, 
which is accompanied by harmful physical or psychological effects. 


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 Medication error: Is any unintentional error in the prescribing, dispensing, or administration of 
a medicinal product by a healthcare professional, patient, or consumer, respectively. The 
administration or consumption of the unassigned treatment and administration of an expired 
product are always reportable as medication errors; cases of subjects missing doses of 
investigational product are not considered reportable as medication errors. 
 Product complaint: Is defined as any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of a drug or device after it is released for distribution. A special situations form 
will only be completed if a complaint is associated with an adverse drug reaction.  
All special situation events as described above must be reported on the Special Situation Report 
form and faxed/emailed to 
 Clinical Safety (contact information listed below) within 
24 hours of knowledge of the event. All AEs associated with these Special Situation Reports 
should be reported as AEs or SAEs as well as recorded on the AE eCRF and/or the SAE report 
form. Details of the symptoms and signs, clinical management, and outcome should be provided, 
when available. 
 
 
 
8.7 
Clinical Laboratory Evaluations 
Clinical laboratory assessments will include clinical chemistry, hematology, and urinalysis. See 
Appendix B for a list of clinical laboratory analytes. 
Subjects will be tested for HIV antibody, hepatitis C virus antibody, and hepatitis B virus surface 
antigen at Screening to determine eligibility. 
Subjects will present to the study site to have a SARS-CoV-2 RNA test administered on Day -2 
(both treatment periods). 
A serum pregnancy test will be performed in all FCBPs at Screening and a urine pregnancy test 
will be performed at Check-In (both treatment periods). 
An FSH test will be performed at Screening in all naturally postmenopausal women to confirm 
menopausal status. 
A blood sample for lipid panel evaluation will be collected after fasting (ie, before first meal of 
the day) at Screening and on Day 2 of both treatment periods. 
A phosphatidyl ethanol blood test will be evaluated at Screening to determine eligibility. 
BAC will be measured via breathalyzer at the timepoints specified in the Schedule of Procedures 
(Appendix A). For more details on the breathalyzer measurements, refer to the Study Procedures 
Manual. 


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8.8 
Vital Signs 
Vital signs will include blood pressure, heart rate, respiratory rate, temperature, and oxygen 
saturation. Vital signs will be measured after a minimum 5-minute rest on Day 1 before each study 
drug administration, and blood pressure, heart rate, and oxygen saturation will be measured 
approximately every 30 minutes after consumption of alcohol until the subject’s BAC returns 
to 0.11 g/100 mL. Vital signs may be measured in the seated or supine position. If there is a 
clinically important change in blood pressure or body temperature from the previous recording 
with values outside the normal range, measurements will be repeated to confirm the change. 
Prior to discharge on Day 2, vital signs will be measured (both treatment periods). 
8.9 
Electrocardiograms 
All 12-lead ECGs will be performed after the subject has been resting in the supine position for at 
least 10 minutes prior to each study drug administration on Days 1 and 2 and prior to discharge on 
Day 2. Repeat ECGs are permitted at the discretion of the Investigator. 
8.10 
Physical Examinations 
A complete physical examination will be performed at Screening (and the Early Termination Visit, 
if applicable) and will consist of general appearance, skin, head, eyes, ears, mouth, oropharynx, 
neck, heart, lungs, abdomen, extremities, and neuromuscular system. Additional body systems 
may be assessed, per Investigator discretion. 
A limited physical examination will be performed at Check-In (both treatment periods) and will 
consist of a minimum of general appearance, skin, heart, lungs, and abdomen. A symptom-based 
physical examination will be performed on Day 1 (pre-dose and post-dose of each study drug 
administration) and Day 2 (pre-dose and post-dose). Additional body systems may be assessed, 
per Investigator discretion. 
Additional physical examinations may be performed, per Investigator discretion. 
Height will be collected at Screening only. Body weight will be collected at Screening and 
Check-In (both treatment periods). Body weight and height will be used to calculate body mass 
index at Screening and Check-In (body mass index is calculated in Treatment Period 1 only). 


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9 
STATISTICS 
9.1 
Analysis Populations 
The Safety Population is defined as all randomized subjects who receive at least 1 dose of study 
drug. 
The PD Population is defined as all subjects who have at least 1 PD measurement. 
9.2 
Statistical Methods 
The statistical analyses to be performed will be further outlined in the Statistical Analysis Plan 
(SAP). The SAP will supersede the protocol if there are any differences between the 2 documents 
in the plans for data analysis, and these differences will be noted in the SAP. 
The study is not formally powered and all endpoints are exploratory in nature. 
In general, categorical variables will be summarized by the count and percentage of subjects. 
Continuous variables will be summarized by the number of non-missing observations, mean, 
standard deviation, median, minimum, and maximum values. 
9.2.1 
Analysis of Efficacy 
 
 
 
 
 
 
 
 
Efficacy data will also be listed and summarized descriptively. 
9.2.2 
Analysis of Demographic and Baseline Characteristics 
Demographic and baseline data will be listed and summarized descriptively. 
9.2.3 
Analysis of Safety 
Safety and tolerability assessments will be listed and summarized descriptively as the observations 
and, when appropriate, as the change from baseline, and shift tables will be produced. 
9.2.4 
Interim Analysis 
No interim analysis is planned for the study. 
9.2.5 
Sample Size Determination 
Approximately 30 subjects are expected to be enrolled in the study. The sample size is not based 
on statistical considerations and is not formally powered as all endpoints are exploratory in nature. 


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10 
DATA MANAGEMENT AND RECORD KEEPING 
10.1 
Data Management 
10.1.1 
Data Handling 
Data will be recorded at the site on eCRFs and reviewed by the CRA during monitoring visits. The 
CRAs will verify data recorded in the EDC system with source documents. All corrections or 
changes made to any study data must be appropriately tracked in an audit trail in the EDC system. 
An eCRF will be considered complete when all missing, incorrect, and/or inconsistent data have 
been accounted for. 
10.1.2 
Computer Systems 
Data will be processed using a validated computer system conforming to regulatory requirements. 
10.1.3 
Data Entry 
Data must be recorded using the EDC system as the study is in progress. All site personnel must 
log into the system using their secure username and password in order to enter, review, or correct 
study data. These procedures must comply with Title 21 of the Code of Federal Regulations 
(21 CFR Part 11) and other appropriate international regulations. All passwords will be strictly 
confidential. 
10.1.4 
Medical Information Coding 
For medical information, the following will be used: 
 Medical Dictionary for Regulatory Activities (latest) for medical history and AEs; and 
 World Health Organization Drug Dictionary for prior and concomitant medications. 
10.1.5 
Data Validation 
Validation checks programmed within the EDC system, as well as supplemental validation 
performed via review of the downloaded data, will be applied to the data in order to ensure 
accurate, consistent, and reliable data. Data identified as erroneous, or data that are missing, will 
be referred to the investigative site for resolution through data queries. 
The eCRFs must be reviewed and electronically signed by the Investigator. 
10.2 
Record Keeping 
Records of subjects, source documents, monitoring visit logs, eCRFs, inventory of study product, 
regulatory documents, and other Sponsor correspondence pertaining to the study must be kept in 
the appropriate study files at the site. Source data are defined as all information in original records 
and certified copies of original records of clinical findings, observations, or other activities in a 
clinical study necessary for the evaluation and reconstruction of the clinical study. Source data are 
contained in source documents (original records or certified copies). These records will be retained 
in a secure file for the period as set forth in the Clinical Study Agreement. Prior to transfer or 
destruction of these records, the Sponsor must be notified in writing and be given the opportunity 
to further store such records.  


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10.3 
End of Study 
The end of the study (“study completion”) is defined as the date of the last protocol-specified 
visit/assessment (including telephone contact) for the last subject in the study. 


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11 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL  
11.1 
Ethical Conduct of the Study 
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for 
designing, conducting, recording, and reporting studies that involve human subjects. Compliance 
with this standard provides public assurance that the rights, safety, and well-being of study subjects 
are protected, consistent with the principles that have their origin in the Declaration of Helsinki, 
and that the clinical study data are credible. 
11.2 
Institutional Review Board 
The IRB will review all appropriate study documentation in order to safeguard the rights, safety, 
and well-being of subjects. The study will only be conducted at sites where IRB approval has been 
obtained. The protocol, Investigator’s Brochure, informed consent form (ICF), advertisements (if 
applicable), written information given to the subjects, safety updates, annual progress reports, and 
any revisions to these documents will be provided to the IRB by the Investigator. 
Federal regulations and International Council for Harmonisation (ICH) Guidelines require that 
approval be obtained from an IRB prior to participation of subjects in research studies. Prior to 
study onset, the protocol, any protocol amendments, ICFs, advertisements to be used for subject 
recruitment, and any other written information regarding this study to be provided to a subject or 
subject’s legal guardian must be approved by the IRB. 
No drug will be released to the site for dosing until written IRB authorization has been received 
by the Sponsor. 
11.3 
Informed Consent 
The ICF and any changes to the ICF made during the course of the study must be agreed to by the 
Sponsor or designee and the IRB prior to its use and must be in compliance with all ICH GCP, 
local regulatory requirements, and legal requirements. 
The Investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study and possible risks associated with participation and must ensure that the 
subject has been informed of his/her rights to privacy. The Investigator will obtain written 
informed consent from each subject before any study-specific activity is performed and should 
document in the source documentation that consent was obtained prior to enrollment in the study. 
The original signed copy of the ICF must be maintained by the Investigator and is subject to 
inspection by a representative of the Sponsor, their representatives, auditors, the IRB, and/or 
regulatory agencies. A copy of the signed ICF will be given to the subject. 
11.4 
Study Monitoring Requirements 
It is the responsibility of the Investigator to ensure that the study is conducted in accordance with 
the protocol, Declaration of Helsinki, ICH GCP, and applicable regulatory requirements, and that 
valid data are entered into the eCRFs. 
To achieve this objective, the CRA’s duties are to aid the Investigator and, at the same time, the 
Sponsor, in the maintenance of complete, legible, well-organized, and easily retrievable data. 
Before the enrollment of any subject in this study, the Sponsor or their designee will review with 
the Investigator and site personnel the following documents: protocol, Investigator’s Brochure, 


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eCRFs and procedures for their completion, informed consent process, and the procedure for 
reporting SAEs. 
The Investigator will permit the Sponsor or their designee to monitor the study as frequently as 
deemed necessary to determine that data recording and protocol adherence are satisfactory. During 
the monitoring visits, information recorded on the eCRFs will be verified against source 
documents and requests for clarification or correction may be made. After the eCRF data are 
entered by the site, the CRA will review the data for safety information, completeness, accuracy, 
and logical consistency. Computer programs that identify data inconsistencies may be used to help 
monitor the clinical study. If necessary, requests for clarification or correction will be sent to 
Investigators. The Investigator and his/her staff will be expected to cooperate with the CRA and 
provide any missing information, whenever possible. 
All monitoring activities will be reported and archived. In addition, monitoring visits will be 
documented at the investigational site by signature and date on the study-specific monitoring log. 
11.5 
Disclosure of Data 
Data generated by this study must be available for inspection by the FDA, the Sponsor or their 
designee, applicable foreign health authorities, and the IRB as appropriate. Subjects or their legal 
representatives may request their medical information be given to their personal physician or other 
appropriate medical personnel responsible for their welfare. 
Subject medical information obtained during the study is confidential and disclosure to third 
parties other than those noted above is prohibited. 
11.6 
Retention of Records 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator 
will keep records, including the identity of all participating subjects (sufficient information to link 
records, eg, eCRFs and hospital records), all original signed ICFs, copies of all eCRFs, SAE forms, 
source documents, and detailed records of treatment disposition. The records should be retained 
by the Investigator according to specifications in the ICH guidelines, local regulations, or as 
specified in the Clinical Study Agreement, whichever is longer. The Investigator must obtain 
written permission from the Sponsor before disposing of any records, even if retention 
requirements have been met. 
If the Investigator relocates, retires, or for any reason withdraws from the study, the Sponsor should 
be prospectively notified. The study records must be transferred to an acceptable designee, such 
as another Investigator, another institution, or to the Sponsor. 
11.7 
Publication Policy 
Following completion of the study, the data may be considered for publication in a scientific 
journal or for reporting at a scientific meeting. Each Investigator is obligated to keep data 
pertaining to the study confidential. The Investigator must consult with the Sponsor before any 
study data are submitted for publication. The Sponsor reserves the right to deny publication rights 
until mutual agreement on the content, format, interpretation of data in the manuscript, and journal 
selected for publication are achieved. 


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11.8 
Financial Disclosure 
Investigators are required to provide financial disclosure information to the Sponsor to permit the 
Sponsor to fulfill its obligations under 21 CFR Part 54. In addition, Investigators must commit to 
promptly updating this information if any relevant changes occur during the study and for a period 
of 1 year after the completion of the study. 


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12 
STUDY ADMINISTRATIVE INFORMATION 
12.1 
Protocol Amendments 
Any amendments to the study protocol will be communicated to the Investigators by 
 or 
the Sponsor. All protocol amendments will undergo the same review and approval process as the 
original protocol. A protocol amendment may be implemented after it has been approved by the 
IRB, unless immediate implementation of the change is necessary for subject safety. In this case, 
the situation must be documented and reported to the IRB within 5 working days. 


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13 
REFERENCES 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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APPENDIX A: SCHEDULE OF PROCEDURES 


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Appendix A: SCHEDULE OF PROCEDURES (Continued) 


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APPENDIX B: CLINICAL LABORATORY ANALYTES 
Standard Safety Chemistry Panel 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Amylase 
Aspartate aminotransferase 
Bicarbonate 
Blood urea nitrogen 
Calcium 
Chloride 
Creatine kinase 
Creatinine 
Direct bilirubin 
Estimated glomerular filtration rate 
Gamma-glutamyl transferase 
Glucose 
Indirect bilirubin 
Inorganic phosphorus 
Lactate dehydrogenase 
Lipase 
Potassium 
Sodium 
Total bilirubin 
Total protein 
Uric acid 
 
Endocrinology 
Follicle-stimulating hormone (FSH) [1] 
 
1. 
An FSH test will be performed at Screening in all naturally postmenopausal women to confirm menopausal status. 
 
Hematology 
Hematocrit 
Hemoglobin 
Platelets 
Red blood cell count 
White blood cell count and differential [1] 
 
1. 
Manual microscopic review is performed only if white blood cell count and/or differential values are out of reference 
range. 
 
Urinalysis 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocyte esterase 
Microscopy [1] 
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
 
1. 
Microscopy is performed only as needed based on positive dipstick test results. 
 
Pregnancy Tests 
Serum human chorionic gonadotropin [1] 
Urine human chorionic gonadotropin [2] 
1. 
A serum pregnancy test will be performed in all females of childbearing potential at Screening. 
2. 
A urine pregnancy test will be performed in all females of childbearing potential at Check-In (both treatment periods). 
 


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Viral Serology 
Hepatitis B virus surface antigen 
Hepatitis C virus antibody 
Human immunodeficiency virus antibody 
Severe acute respiratory syndrome 
coronavirus-2 RNA 
 
Urine Drug Screen 
3,4-methylenedioxy-methamphetamine 
Amphetamines 
Barbiturates 
Benzodiazepines 
Cannabinoids 
Cocaine 
Cotinine 
Methadone 
Methamphetamine 
Opioids 
Oxycodone 
Phencyclidine 
Tricyclic antidepressants 
 
 
Lipid Panel 
High-density lipoprotein cholesterol 
Low-density lipoprotein cholesterol 
Total cholesterol 
Triglycerides 
 
Other Tests 
Blood phosphatidyl ethanol 
Blood ethanol 
 
 


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APPENDIX C: SYMPTOM ASSESSMENT SCALES 
 


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Alcohol Toxicity Symptom Scale 
 

SAP_001.pdf: