Conditions: Classic Galactosemia
Keywords: Classic Galactosemia Aldose Reductase Inhibition Galactose, Galactitol
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 114
Healthy volunteers: yes

Brief summary:
This study is a first-in-human, randomized, placebo-controlled, 4-Part, single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy adult subjects and adult subjects with Classic Galactosemia.

Detailed description:
The study is designed to assess the safety and PK of AT-007 in healthy subjects and subjects with Classic Galactosemia as well as the effect of AT-007 on biomarkers of galactose metabolism (galactose, galactitol, and other galactose metabolites) in subjects with Classic Galactosemia.

This study consists of 4 parts:

* Part A (SAD) in 32 healthy subjects. Once daily oral escalating dose (6 active, 2 placebo).
* Part B and C (MAD for 7 days) in 36 healthy subjects. Once daily multiple daily dosing (8 active, 2 placebo per each dose cohort).
* Part D (SAD followed by MAD for 27 days) in 18 subjects with Classic Galactosemia. Once daily followed by multiple daily oral dosing (6 active, 2 placebo for each dose cohort).

Arms:
arm 1: AT-007 is a CNS and retina penetrant aldose reductase inhibitor. arm 2: Placebo is used as a comparator to the experimental arm.

Interventions: intervention 1: AT-007 intervention 2: Placebo
Intervention descriptions: intervention 1: AT-007 will be administered once daily before breakfast. Up to 4 different dose cohorts in part A; up to 4 dose cohorts in part B, up to 2 dose cohorts for part C, and up to 3 dose cohorts for part D will be enrolled in the study. The starting dose in Part A will be 0.5 mg/kg as a single dose. Subsequent doses in Part A and all doses in Parts B, C, and D will be based on the results of previous cohorts and/or previous parts of the study. Part B will start after all subjects in Part A have completed the study. Cohort C1 will be conducted simultaneously with Cohort B3 and using the same dose as Cohort B2. The dose for Cohort D1 will not be higher than the dose for Cohort B2. The second and third cohorts in Part D (D2 and D3) will not start until after all subjects in Cohorts B3 and B4, respectively, have completed the study and the dose levels will not be higher than those for Cohorts B3 and B4, respectively. intervention 2: Matching placebo will be administered once in the morning before breakfast

Protocol document:
Prot_000.pdf: 
 
 
 
Page 1 of 1 
February 14, 2023 
 
To Whom It May Concern: 
This is the protocol for the below mentioned study. 
Study Title: A Phase 1-2, dose-escalating, 6-part study to evaluate the safety and pharmacokinetics 
and pharmacodynamics of single and multiple doses of AT-007 in healthy adult subjects and adult 
subjects with Classic Galactosemia (CG) or GALK Deficient Galactosemia 
 
NCT: NCT04117711 
 
Document Date of Protocol: 03 September 2021 
 
Please contact me with any questions. 
 
Respectfully, 
 
 
Evan Bailey, MD 
Exective Clinical Director 
 
 
 
 
 
 
 
 
 


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CURRENT STUDY PROTOCOL 
 
 
A Phase 1-2, Dose-Escalating, 6-Part Study to Evaluate the Safety 
and Pharmacokinetics of Single and Multiple Doses of AT-007 in 
Healthy Adult Subjects and Adult Subjects with Classic 
Galactosemia (CG) or GALK-deficient Galactosemia 
 
 
Protocol Number 
AT-007-1001 
Version 10.0 
3 September 2021 
 
 
IND Number: 139699 
 
 
 
 
 
Applied Therapeutics Inc. 
340 Madison Avenue | 19th Floor  
New York, NY 10173 
USA 
 
 
 
 
 
 
 
 
 
CONFIDENTIALITY STATEMENT 
The confidential information in this document is provided to you as an Investigator or 
consultant for review by you, your staff, and the applicable Institutional Review Board. Your 
acceptance of this document constitutes agreement that you will not disclose the information 
herein to others without written authorization from CRO and Applied Therapeutics Inc. except 
to the extent necessary to obtain informed consent from persons who participate as subjects in 
this study. 
 
 


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PROTOCOL APPROVAL PAGE 
 
A Phase 1-2, Dose-Escalating, 6-Part Study to Evaluate the Safety and Pharmacokinetics of 
Single and Multiple Doses of AT-007 in Healthy Adult Subjects and Adult Subjects with Classic 
Galactosemia (CG) or GALK-deficient Galactosemia 
 
Protocol Number: AT-007-1001 
Sponsor: Applied Therapeutics Inc. 
Sponsor Contact: 
¶ Riccardo Perfetti, MD, PhD 
Applied Therapeutics Inc. 
Chief Medical Officer, 
340 Madison Avenue, 19th Floor 
New York, New York 10173 
Phone: (+1) 212-220-9227 
rperfetti@appliedtherapeutics.com  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
_______________________________________________________________ 
 
 
 
 
 
(Signature) 
 
 
 
 
 
 
 
 
 
(3-Sep-2021) 
 
 
Principal 
Investigator: 
 
 
______________________________________________________________ 
 
 
 
 
 
(Signature) 
 
 
 
 
 
 
 
 
 
 
(Date) 
 
 


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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: Applied Therapeutics Inc. 
Name of Active Ingredient: AT-007 
Title of Study: A Phase 1-2, Dose-Escalating, 6-Part Study to Evaluate the Safety and 
Pharmacokinetics of Single and Multiple Doses of AT-007 in Healthy Adult Subjects and Adult 
Subjects with Classic Galactosemia (CG) or GALK-deficient Galactosemia 
Study Center: The study will be conducted at up to 6 sites in the United States (US) and up to 3 sites 
in Europe. 
Phase of Development: 1-2 
Study Objectives: 
Primary: 
• 
To evaluate the safety of single and multiple ascending doses of orally administered 
AT-007 in healthy adult subjects and adult subjects with CG or GALK-deficient 
Galactosemia  
Secondary: 
• 
To evaluate the pharmacokinetic (PK) parameters of single and multiple doses of orally 
administered AT-007 in healthy adult subjects and adult subjects with CG or GALK-
deficient Galactosemia 
• 
To evaluate the effect of single and multiple doses of orally administered AT-007 on the 
level of galactitol, a biomarker of aldose reductase (AR) activity, in adult subjects with CG 
or GALK-deficient Galactosemia 
• 
To evaluate the effect of single and multiple doses of orally administered AT-007 on the 
levels of galactose and its other metabolites in adult subjects with CG or GALK-deficient 
Galactosemia 
Exploratory: 
• 
To measure the levels of AT-007 in the cerebrospinal fluid (CSF) of healthy adult subjects 
Study Design:  
This study is a first-in-human, randomized, placebo-controlled, 6-Part, single ascending dose (SAD) 
and multiple ascending dose (MAD) study in healthy adult subjects and adult subjects with CG or 
GALK-deficient Galactosemia. The study is designed to assess the safety and PK of AT-007 in healthy 
subjects and subjects with CG or GALK-deficient Galactosemia as well as the effect of AT-007 on 
biomarkers of galactose metabolism (galactose, galactitol, and other galactose metabolites) in subjects 
with CG or GALK-deficient Galactosemia.  
This study consists of 6 parts: 
• 
Part A (SAD) in 40 healthy subjects: 5 double-blind cohorts of 8 subjects (6 active and 2 
placebo) each 
• 
Part B (MAD for 7 days) in 28 healthy subjects: 2 double-blind cohorts of 8 subjects (6 active 
and 2 placebo) each and 2 double-blind cohorts of 6 subjects (4 active and 2 placebo) each 
• 
Part C (MAD for 7 days) in 12 healthy subjects: 3 cohorts of 4 subjects each (open-label 
AT-007) 


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• 
Part D (SAD followed by 5-day washout followed by MAD for 27 days in up to 18 subjects 
with CG: 3 cohorts of 6 subjects (4 active and 2 placebo) each (the clinical site staff and the 
subjects will be blinded to study treatment).  
• 
Part E (SAD followed by 5-day washout followed by MAD for 27 days) in up to 18 subjects 
with GALK-deficient Galactosemia: 1 to 3 cohorts of 6 subjects (4 active and 2 placebo) each 
(the clinical site staff and the subjects will be blinded to study treatment) 
• 
Part D Extension for 90 days in up to 28 subjects (up to 21 active and 7 placebo) with CG in up 
to 2 cohorts (the clinical site staff and the subjects will be blinded to study treatment) 
Note: In Parts D and E, overall number of subjects per cohort may be increased up to 8 subjects to 
address any potential lost-to-follow-up among subjects treated with either placebo or AT-007. 
For all cohorts in all parts (A, B, C, D, and E), the study consists of a Screening Period (28 days 
[Day -28 to Day -1] for Parts A, B, and C and 40 days [Day -40 to Day -1] for Parts D and E [and 
D Extension for de novo subjects who did not participate in Part D and subjects whose last visit in 
Part D was >60 days before Day 1 in the Part D Extension]), a period of study treatment and associated 
assessments, and an end of study (EOS) or end of extension (EOE) Visit (28 days after the last dose of 
study drug). Subjects will be randomized and receive the first dose of study drug on Day 1. At a 
minimum, subjects will remain at the clinical research unit (CRU) through 24 hours after the first dose. 
Subjects in Part A will have one in-clinic stay during the Treatment Period with the single dose taken 
in the CRU. Subjects in Parts B and C will have 1 in-clinic stay with all 7 doses taken in the CRU. 
Subjects in Parts D and E will have 3 in-clinic stays with most doses taken at home. Safety will be 
monitored and blood samples will be collected for PK in all parts of the study. Also, subjects in 
selected dose cohorts of Parts A (SAD) and D (SAD portion only) will have urine collected for PK. In 
addition, subjects in Part C will have one lumbar puncture for CSF collection. Also, subjects in Parts D 
and E will have blood samples and urine collected for biomarkers of galactose metabolism.  
The 90-day Part D Extension (separate informed consent required) is open for subjects with CG who 
completed Part D, participated in but did not complete Part D for reasons other than study drug related 
treatment emergent adverse event (related TEAE), or did not participate in Part D. Subjects who 
previously completed Part D may participate in the 90-day Extension at any time after the EOS Visit 
(scheduled for 28 days after the last dose in Part D MAD). Subjects who participated in but did not 
complete Part D may participate in the Extension after either the EOS Visit (if they have this visit and 
it occurs beyond 14 days after the last dose) or a minimum 2-week wash-out period after the last dose 
received in Part D (if they do not have the EOS Visit or have it before 2 weeks after the last dose). 
Subjects with CG who have not previously participated in Part D may be prescreened (optional) and 
participate in the 90-day Extension after they undergo all the required screening procedures from 
Day -60 to Day -1. Subjects with last visit in Part D more than 60 days before Day 1 in Part D 
Extension will also need a screening visit although some screening procedures done before Part D do 
not need to be repeated. Subjects in the Part D Extension will be randomized in a 3:1 ratio to active 
drug at the daily dose of 20 mg/kg or placebo. Most doses during the Part D Extension will be taken at 
home, but there are 2 in-clinic stays. A second cohort may be initiated in the Part D Extension to 
evaluate a dose higher than 20 mg/kg/day. If so, subjects will be randomized in a 3:1 ratio to active 
drug or placebo and will take most doses at home, except for 2 in-clinic stays. Also, subjects in Part D 
Extension will have blood samples collected for both PK and biomarkers of galactose metabolism. 
The starting dose in Part A was 0.5 mg/kg as a single dose. Subsequent doses in Part A and all doses in 
Parts B, C, D, and E are based on the results of previous cohorts and/or previous parts of the study. 
Part A of the study started first. Part A Cohort 5 (40 mg/kg single dose) was recently added to the 
protocol (version 4.0) and results showed the dose was safe and well tolerated. Part B started after all 
subjects in Cohorts A1 through A4 completed the study (minus the EOS Visit). Given that the results 
for 40 mg/kg in Cohort A5 were acceptable, Part B Cohort 4 (40 mg/kg) will start with this version of 
the protocol (version 5.0). The first cohort in Part C (C1) started after both safety and PK data from 


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Cohorts B1 and B2 were reviewed. Cohort C1 was conducted simultaneously with Cohort B3 and used 
the same dose as Cohort B2 (10 mg/kg). The second cohort in Part C (C2) started after safety and PK 
data from Cohort B3 were reviewed and used the same dose as Cohort B3 (20 mg/kg); safety and PK 
results for Cohort C1 were also considered before starting Cohort C2. The third cohort in Part C (C3) 
will start with this version of the protocol (version 5.0) and use the same dose as Cohort B4 (given the 
results from Cohort A5); safety and PK results for Cohort C2 were also considered before starting 
Cohort C3. The first cohort in Part D (D1) started after all subjects in Cohorts A1 through A4 
completed the study including the EOS Visit and all subjects in Cohorts B1 and B2 completed the 
study (minus the EOS Visit). The dose for Cohort D1 (5 mg/kg) was not higher than the dose for 
Cohort B2 (10 mg/kg). The second cohort in Part D (D2) started after all subjects in Cohort B3 
completed the study (minus the EOS Visit) and the dose level (20 mg/kg) was the same as that for 
Cohort B3. The third cohort in Part D (D3) will start after all subjects in Cohort B4 complete the study 
(minus the EOS Visit) and the dose level will not be higher than the 40 mg/kg dose used for Cohort B4. 
The starting dose for Part E (Cohort E1) will be the most clinically appropriate dose as determined by 
the evaluation of available safety, tolerability, and PD (reduction in galactitol level) in Part D and the 
dose will not be higher than the highest acceptable dose in Part D at the time of starting Part E (after all 
subjects complete Cohorts D1 and D2 but may be before, during, or after Cohort D3). The Safety 
Review Committee (SRC) reviewed/will review safety data before each dose escalation and before the 
start of Parts B, C, D, and E. Also, the Sponsor reviewed/will review all PK and galactitol data as they 
become available. 
The dose for the first cohort of the Part D Extension (DE1) will be 20 mg/kg/day based on acceptable 
SAD and MAD safety and PK data from Cohort D2. After SRC review of all SAD and MAD data and 
Sponsor review of PK and galactitol data for Cohorts D1 through D3, a second cohort of the Part D 
Extension (DE2) may be initiated to evaluate a dose higher than 20 mg/kg/day if this dose was well 
tolerated in the SAD and MAD portions of the study in both healthy volunteers and subjects with CG.  
The review of the PK data from Cohorts A1 through A4 and the first 2 cohorts of Part B confirmed that 
once daily (QD) dosing is adequate.  
Number of Subjects: Up to 80 healthy subjects, between 18 and 46 subjects with CG depending on 
the number of Part D Extension subjects who are or are not the same subjects as those in Part D, and up 
to 18 subjects with GALK-deficient Galactosemia are planned to be enrolled. More subjects may be 
enrolled if the number of cohorts increases to study AT-007 doses >40 mg/kg. Also, more subjects 
may be enrolled if the overall number of subjects per cohort in Parts D and E are increased up to 
8 subjects to address any potential lost-to-follow-up among subjects treated with either placebo or 
AT-007. 
Diagnosis and Main Study Entry Criteria for Parts A, B, and C: 
Healthy male or non-pregnant, non-lactating female adult between 18 and 65 years of age, inclusive 
Diagnosis and Main Study Entry Criteria for Part D and Part D Extension: 
Male and non-pregnant, non-lactating female adult between the ages of 18 and 65 years, inclusive, with 
a Classic Galactosemia (CG) diagnosis confirmed by evidence of absent or significantly decreased 
(<1%) galactose-1-phosphate uridylyltransferase (GALT) activity in red blood cells or by historical 
record of diagnosis of GALT deficiency (medical record or gene analysis report or written 
communication by health care professional), who have no other significant health problems unrelated 
to CG. 
For the Part D Extension, subjects who previously participated in but did not complete Part D must not 
have discontinued Part D because of study drug related TEAE(s). 


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Diagnosis and Main Study Entry Criteria for Part E: 
Male and non-pregnant, non-lactating female adult between the ages of 18 and 65 years, inclusive, with 
a GALK-deficient Galactosemia diagnosis documented by historical record of either absent or 
significantly decreased galactokinase (GALK) activity in red blood cells (medical record, enzyme 
activity report, genetic mutation report, or written communication by health care professional), who 
have no other significant health problems unrelated to GALK-deficient Galactosemia.  
Investigational Product, Dosage and Mode of Administration: 
AT-007 (capsules or liquid suspension; single and multiple oral doses): once daily [QD] under fasting 
conditions for up to 7 days in healthy subjects; up to 27 days in subjects with CG who tolerated a 
previous single dose (and up to 90 days during an Extension); and up to 27 days in subjects with 
GALK-deficient Galactosemia who tolerated a previous single dose. Doses between 0.5 and 40 mg/kg, 
oral, were administered in Part A of the study. Dose levels in subsequent parts of the study are based on 
the safety, PK, and galactitol (Parts D and E only) results of previous cohorts and/or previous parts of 
the study. Doses higher than 40 mg/kg may be evaluated if the human maximum observed 
concentration (Cmax) and area under the curve (AUC) are substantially lower than the corresponding 
values calculated in nonclinical experiments and no dose limiting toxicity (DLT) is observed up to and 
including at the 40 mg/kg dose. If dose escalation above 40 mg/kg is feasible based on the above 
criteria, these higher doses may be investigated in additional SAD and MAD cohorts in healthy 
subjects and in subjects with Galactosemia if no AT-007 levels are detected in the CSF collected from 
the healthy subjects enrolled in Cohort C3. Doses will be rounded according to the available SKU as 
described in the Pharmacy Manual 
Duration of Treatment: Subject participation will be a maximum of approximately 56, 63, 63, 100, 
and 100 days (from screening through EOS Visit) for Parts A, B, C, D, and E, respectively. For 
subjects in the Part D Extension who did not previously participated in Part D (SAD and/or MAD), 
study participation will be a maximum of approximately 178 days (screening through EOE Visit at 
28 days after the last dose of study drug during the extension). For subjects in the Part D Extension 
who previous participated in Part D (SAD and MAD), study participation will be a maximum of 
approximately 218 days (SAD and MAD) (screening through EOE Visit), assuming no re-screening 
needed for Part D Extension and not counting the wash-out period between the end of Part D MAD and 
the initiation of Part D Extension. 
Reference Therapy, Dosage and Mode of Administration: Matching placebo (capsules or liquid 
suspension) will be administered under the same conditions and on the same schedule as the 
investigational product in Parts A, B, D, E, and D Extension. Part C is open-label AT-007 (no placebo).  
Concomitant Medications and Dietary Restrictions:  
The following medications are prohibited within 5 half-lives prior to the first dose of study 
drug through the last dose of study drug: 1) sensitive substrates of Breast Cancer Resistance 
Protein (BCRP) (e.g., rosuvastatin, sulfasalazine) or potent inhibitors of BCRP (e.g., 
cyclosporine A); 2)  sensitive substrates of Organic Anion Transporter (OAT)1 and OAT3 
(e.g., famotidine, adefovir, furosemide, ganciclovir, cefaclor, ceftizoxime, pen-G); 3) sensitive 
substrates of cytochrome P450 3A4 (CYP3A4) (e.g. midazolam, triazolam, buspirone, 
alfentanil, dronedarone, eletriptan, conivaptan, lovastatin, simvastatin), or CYP2B6 (e.g. 
bupropion), or CYP2C19 (e.g. omeprazole), or CYP1A2 (e.g. alosetron, caffeine, duloxetine, 
melatonin, ramelteon, tasimelteon,tizanidine). 
Drugs potentially associated with transaminase elevations, such as mirtazapine, are prohibited 
within 5 half-lives prior to the first dose of study drug through the last dose of study drug. 


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The following potentially nephrotoxic drugs are prohibited within < 5 half-lives prior to the 
first dose of study drug through the last dose of study drug: amitriptyline, aspirin, doxepin, 
lithium, amphotericin B, foscarnet, ganciclovir, pentamidine, rifampin, antiretrovirals (e.g. 
adefovir, tenofovir), calcineurin inhibitors (e.g. cyclosporine, tacrolimus), angiotensin-
converting enzyme inhibitors, angiotensin receptor blockers, clopidogrel, ticlopidine, 
pamidronate, zoledronate, statins, chemotherapeutics, contrast dye, loop diuretics, thiazides, 
triamterene, allopurinol, gold therapy, haloperidol, quinine, ranitidine. 
In Parts D, E, and D Extension, subjects will be allowed to take concomitant medications for 
Galactosemia complications provided that these concomitant medications are reviewed/approved by 
the Investigator and that the subjects are on stable doses for at least a month prior to screening (or first 
dose of study drug if no screening visit) through the EOS or EOE Visit. 
Study Endpoints:  
Primary Endpoints 
The primary endpoints of this study are overall safety and adverse events (AEs). Safety will be 
assessed by the following: 
• 
AEs 
• 
Clinical safety laboratory tests (hematology, chemistry, urinalysis) 
• 
Physical examinations 
• 
Vital signs 
• 
Electrocardiograms (ECGs) 
Secondary Endpoints 
• 
PK parameters in healthy subjects, subjects with CG, and subjects with GALK-deficient 
Galactosemia 
• 
Galactose, galactitol, and other galactose metabolites in the blood of subjects with CG and 
subjects with GALK-deficient Galactosemia 
• 
Urine galactitol for subjects with CG and subjects with GALK-deficient Galactosemia 
Exploratory Endpoints: 
• 
AT-007 level in the CSF of healthy subjects (Part C only) 
Statistical Methods: 
Sample Size: The sample size was determined outside of statistical considerations. The number of 
subjects is typical for Phase 1 studies of this type and is adequate to meet study objectives. 
Safety Analyses:  
The evaluation of safety will be based on the occurrence of TEAEs; discontinuations from study drug 
and/or the study because of AEs; clinical safety laboratory test results, physical examination findings, 
vital sign evaluations, and 12-lead ECGs results. All safety endpoints will be summarized 
descriptively. No statistical inference will be applied to the safety endpoints. Descriptive statistics will 
be calculated for quantitative safety data and frequency counts will be compiled for qualitative safety 
data. 


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PK Analyses:  
PK calculations will be performed using appropriate software, e.g., Phoenix™ WinNonlin® 
(Version 6.3 or higher, Pharsight Corporation) and/or SAS® (Version 9.4 or higher, SAS Institute Inc.). 
PK parameters will be calculated using noncompartmental methods, using an appropriate model. 
Concentrations below the lower limit of quantitation (BLQ) will be treated as zero from the time of the 
first quantifiable concentration; embedded and terminal BLQ concentrations will be treated as 
“missing.” Actual sample times, if available, will be used in the PK analysis. 
AT-007 concentration-time data and PK parameters will be summarized by study part and cohort (dose 
level) using descriptive statistics (n, mean, standard deviation [SD], median, minimum, maximum, 
percent coefficient of variation [CV%]). 
Dose proportionality, the proportionality of a change in systemic exposure with a change in dose, may 
be assessed using a power model or other appropriate methods. 
Details of the PK analyses, including any additional exploratory analyses, will be provided in the 
Statistical Analysis Plan (SAP). 
PK samples will be stored for possible future analysis of AT-007 metabolites. 
Biomarker Analyses:  
For Parts D, E, and D Extension, blood and/or urine levels of galactose and/or its metabolites 
(including galactitol) will be summarized using descriptive statistics. Details of these analyses will be 
provided in the SAP. 
 
 
 


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TABLE OF CONTENTS 
PROTOCOL APPROVAL PAGE ...................................................................................................2 
PROTOCOL SYNOPSIS.................................................................................................................3 
TABLE OF CONTENTS .................................................................................................................9 
LIST OF ABBREVIATIONS ........................................................................................................15 
1................. INTRODUCTION ......................................................................................................18 
1.1.............. Background .................................................................................................................18 
1.1.1........... Galactosemia Types, Treatment, Prevalence, and Symptoms ....................................18 
1.1.2........... GALT Deficiency (Includes Classic Galactosemia) ...................................................19 
1.1.3........... GALK Deficiency .......................................................................................................20 
1.1.4........... Enzyme Defects and Mechanisms of Disease ............................................................21 
1.1.5........... Clinical Management of Galactosemia .......................................................................22 
1.1.6........... Galactosemia Prevalence ............................................................................................23 
1.2.............. Development of Aldose Reductase Inhibitors (ARIs) ................................................23 
1.3.............. Choice of Study Population ........................................................................................23 
1.4.............. Dose Rationale ............................................................................................................24 
2................. OBJECTIVES AND ENDPOINTS ............................................................................26 
3................. INVESTIGATIONAL PLAN .....................................................................................27 
3.1.............. Overall Study Design ..................................................................................................27 
3.2.............. Rationale for Overall Study Design ............................................................................32 
3.3.............. Study Drug Administration Schedules .......................................................................32 
3.3.1........... Part A: Double-blind Single Ascending Dose (SAD) in Healthy Subjects ................33 
3.3.2........... Part B: Double-blind Multiple Ascending Dose (MAD) in Healthy Subjects ...........34 
3.3.3........... Part C: Open-label Multiple Ascending Dose (MAD) in Healthy Subjects ...............34 
3.3.4........... Part D: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) 
in Subjects with Classic Galactosemia (CG) ..............................................................35 
3.3.5........... Part E: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) 
in Subjects with GALK-deficient Galactosemia ........................................................36 
3.3.6........... Part D Extension: 90-Day Dosing in Subjects with Classic Galactosemia ................37 
3.4.............. Safety Review Committee (SRC) ...............................................................................38 
3.5.............. Dose Escalation/De-escalation ...................................................................................41 
3.6.............. Study Termination ......................................................................................................42 
4................. SELECTION OF SUBJECTS ....................................................................................44 


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4.1.............. Healthy Subjects in Study Parts A, B, and C ..............................................................44 
4.1.1........... Inclusion Criteria ........................................................................................................44 
4.1.2........... Exclusion Criteria .......................................................................................................44 
4.2.............. Subjects with Classic Galactosemia (CG) in Study Part D and Part D 
Extension ....................................................................................................................46 
4.2.1........... Inclusion Criteria ........................................................................................................46 
4.2.2........... Exclusion Criteria .......................................................................................................47 
4.3.............. Subjects with GALK-deficient Galactosemia in Study Part E ...................................48 
4.3.1........... Inclusion Criteria ........................................................................................................48 
4.3.2........... Exclusion Criteria .......................................................................................................48 
4.4.............. Subject Participation in Multiple Cohorts ..................................................................48 
4.5.............. Subject Discontinuation Criteria .................................................................................49 
4.6.............. Medication and Activity Restrictions .........................................................................49 
4.7.............. Contraception Requirements ......................................................................................51 
5................. STUDY TREATMENTS ............................................................................................53 
5.1.............. Study Drug Supplies ...................................................................................................53 
5.2.............. Study Drug Assignment and Blinding ........................................................................53 
5.3.............. Study Drug Administration .........................................................................................54 
5.4.............. Treatment Compliance ................................................................................................54 
5.5.............. Fasting/Meals/Beverages ............................................................................................55 
6................. STUDY PROCEDURES BY VISIT ..........................................................................56 
6.1.............. Prescreening Period (De novo Part D Extension Subjects Only) ...............................56 
6.2.............. Screening Period (Days -28 through -1 for Parts A, B, and C and Days -40 
through -1 for Parts D and E, and Days -60 through -1 for Part D Extension) ..........57 
6.3.............. Clinical Research Unit (CRU) Check-in (All Parts, Day -1) ......................................59 
6.4.............. Day 1 through Penultimate Visit (Part A, Days 1 through 4) .....................................60 
6.4.1........... Day 1 (Study Drug Dosing Day) ................................................................................60 
6.4.2........... Days 2 and 3 ...............................................................................................................60 
6.4.3........... Day 4 ...........................................................................................................................61 
6.5.............. Day 1 through Penultimate Visit (Part B, Days 1 through 9) .....................................61 
6.5.1........... Day 1 (First Study Drug Dosing Day) ........................................................................62 
6.5.2........... Day 2 (Study Drug Dosing Day) ................................................................................62 
6.5.3........... Days 3, 4, and 5 (Study Drug Dosing Days) ..............................................................62 


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6.5.4........... Day 6 (Study Drug Dosing Day) ................................................................................63 
6.5.5........... Day 7 (Last Study Drug Dosing Day) ........................................................................63 
6.5.6........... Days 8 and 9 ...............................................................................................................63 
6.6.............. Day 1 through Penultimate Visit (Part C, Days 1 through 9) .....................................64 
6.7.............. Day 1 through Penultimate Visit (Parts D and E, Days 1 through 34) .......................64 
6.7.1........... Day 1 (Single Dose) ....................................................................................................64 
6.7.2........... Non-dosing Days Between Single and Multiple Dosing (Days 2 through 5) .............65 
6.7.2.1........ Day 2 ...........................................................................................................................65 
6.7.2.2........ Day 3 ...........................................................................................................................66 
6.7.2.3........ Day 4 (Cohort D3 Only) .............................................................................................66 
6.7.3........... Day 6 (First Study Drug Dosing Day for Multiple Dosing Period)............................66 
6.7.4........... Day 12 (Check-in for Second In-clinic Period) ..........................................................67 
6.7.5........... Day 13 (Discharge from Second In-clinic Period) .....................................................68 
6.7.6........... Day 20 (Out-patient Visit in the Middle of the Multiple Dosing Period) ..................68 
6.7.7........... Day 32 (Check-in for Third In-clinic Period and Last Study Drug Dosing 
Day of the Multiple Dosing Period) ...........................................................................69 
6.7.8........... Day 33 .........................................................................................................................70 
6.7.9........... Day 34 (Discharge from Third In-clinic Period) ........................................................70 
6.8.............. Day 1 through Penultimate Visit (Part D Extension, Days 1 through 91) ..................71 
6.8.1........... Day 1 ...........................................................................................................................71 
6.8.2........... Day 2 ...........................................................................................................................72 
6.8.3........... Day 30, and Day 60 ....................................................................................................72 
6.8.4........... Day 90 (Check-in for Second In-clinic Period and Last Study Drug Dosing 
Day) ............................................................................................................................73 
6.8.5........... Day 91 (Discharge from Second In-clinic Period) .....................................................74 
6.9.............. EOS or EOE Visit (28 Days After the Last Dose) ......................................................74 
6.10............ Unscheduled Visit .......................................................................................................75 
7................. STUDY ASSESSMENTS ..........................................................................................76 
7.1.............. Safety Assessments .....................................................................................................76 
7.1.1........... Adverse Events ...........................................................................................................76 
7.1.2........... Clinical Laboratory Tests ...........................................................................................76 
7.1.3........... Physical Examinations ................................................................................................77 
7.1.4........... Vital Signs ..................................................................................................................77 


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7.1.5........... Electrocardiograms (ECGs) ........................................................................................77 
7.1.6........... Prior and Concomitant Medications ...........................................................................77 
7.1.7........... Pregnancy ...................................................................................................................78 
7.1.8........... Other Safety Measures ................................................................................................78 
7.2.............. Pharmacokinetic (PK) Assessments ...........................................................................78 
7.3.............. Assessments of Biomarkers of Galactose Metabolism ...............................................81 
8................. ADVERSE EVENTS ..................................................................................................82 
8.1.............. Definitions ..................................................................................................................82 
8.1.1........... Adverse Event (AE) ....................................................................................................82 
8.1.2........... Serious Adverse Event (SAE) ....................................................................................82 
8.1.3........... Expectedness ...............................................................................................................83 
8.2.............. AE Reporting ..............................................................................................................83 
8.2.1........... AE Severity .................................................................................................................83 
8.2.2........... AE Relationship to Study Drug ..................................................................................84 
8.3.............. SAE Reporting ............................................................................................................84 
9................. STATISTICS ..............................................................................................................86 
9.1.............. Sample Size Determination ........................................................................................86 
9.2.............. Statistical Methods ......................................................................................................86 
9.2.1........... General Considerations ...............................................................................................86 
9.2.2........... Analysis Populations ..................................................................................................87 
9.2.3........... Subject Disposition .....................................................................................................87 
9.2.4........... Drug Exposure and Compliance .................................................................................87 
9.2.5........... Important Protocol Deviations ....................................................................................87 
9.2.6........... Demographic and Baseline Characteristics ................................................................88 
9.2.7........... Safety Analyses ..........................................................................................................88 
9.2.8........... Pharmacokinetic (PK) Analyses .................................................................................88 
9.2.9........... Biomarker Analyses ....................................................................................................88 
9.2.10......... Efficacy Analyses .......................................................................................................89 
10............... GENERAL CONSIDERATIONS ..............................................................................90 
10.1............ Ethical and Regulatory Considerations ......................................................................90 
10.1.1......... Study Conduct ............................................................................................................90 
10.1.2......... Institutional Review Boards (IRBs) and Independent Ethics Committees 
(IECs) ..........................................................................................................................90 


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10.1.3......... Informed Consent .......................................................................................................90 
10.2............ Data Collection, Monitoring, Management, and Quality Assurance ..........................90 
10.3............ Study Documentation .................................................................................................91 
10.4............ Miscellaneous Administrative Information ................................................................91 
10.5............ Facilities ......................................................................................................................91 
11............... REFERENCES ...........................................................................................................93 
APPENDIX A. SCHEDULE OF ASSESSMENTS FOR PART A (SAD IN 
HEALTHY SUBJECTS) ............................................................................................95 
APPENDIX B. SCHEDULE OF ASSESSMENTS FOR PART B (MAD IN 
HEALTHY SUBJECTS) ............................................................................................98 
APPENDIX C. SCHEDULE OF ASSESSMENTS FOR PART C (MAD IN 
HEALTHY SUBJECTS) ..........................................................................................101 
APPENDIX D. SCHEDULE OF ASSESSMENTS FOR PART D (SAD AND MAD 
IN SUBJECTS WITH CLASSIC GALACTOSEMIA) ...........................................104 
APPENDIX E. SCHEDULE OF ASSESSMENTS FOR PART E (SAD AND MAD 
IN SUBJECTS WITH GALK-DEFICIENT GALACTOSEMIA) ...........................108 
APPENDIX F. SCHEDULE OF ASSESSMENTS FOR PART D EXTENSION ..................112 
APPENDIX G. GUIDANCE IN CASE OF INCREASE IN ALT OR AST ............................116 
APPENDIX H. GUIDANCE IN CASE OF WORSENING RENAL FUNCTION .................118 
APPENDIX I. RESULTS OF IN-VITRO DRUG-DRUG-INTERACTION (DDI) 
STUDIES WITH AT-007 .........................................................................................119 
 
 


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LIST OF TABLES 
Table 1: ...... Study Design ...............................................................................................................27 
Table 2: ...... SAD Dose Cohorts in Healthy Subjects (Part A) .......................................................34 
Table 3: ...... MAD Dose Cohorts in Healthy Subjects (Part B) ......................................................34 
Table 4: ...... MAD Dose Cohorts in Healthy Subjects with CSF Collection (Part C) ....................35 
Table 5: ...... Dose Cohorts in Subjects with Classic Galactosemia (Part D) ..................................36 
Table 6: ...... Dose Cohort in Subjects with GALK-deficient Galactosemia (Part E)......................37 
Table 7: ...... 90-Day Dose Cohort in Subjects with Classic Galactosemia (Part D 
Extension) ...................................................................................................................38 
Table 8: ...... PK Parameters of AT-007 After a Single Dose in Healthy Subjects (Part A) 
and Subjects with Classic Galactosemia (SAD Period of Parts D and E) ..................79 
Table 9: ...... PK Parameters of AT-007 During Multiple Dosing in Healthy Subjects 
(Parts B and C) and Subjects with Galactosemia (MAD Period of Parts D 
and E and Part D Extension) .......................................................................................80 
 
LIST OF FIGURES 
Figure 1: .... The Leloir Pathway and Alternative Route of Galactose Metabolism .......................19 
Figure 2: .... Study Schematic .........................................................................................................28 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition or Explanation 
AE 
Adverse event 
ADP 
Adenosine diphosphate 
ALP 
Alkaline phosphatase 
ALT 
Alanine transaminase 
AR 
Aldose reductase 
ARI 
Aldose reductase inhibitor 
AST 
Aspartate transaminase 
ATP 
Adenosine triphosphate 
AUC 
Area under the curve 
BCRP 
Breast cancer resistance protein 
BMD 
Bone marrow density 
BMI 
Body mass index 
BLQ 
Below the limit of quantitation 
BSA 
Body surface area 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations (in US) 
CG 
Classic Galactosemia 
CI 
Confidence interval 
CLIA 
Clinical Laboratory Improvement Amendments 
Cmax 
Maximum observed concentration 
CNS 
Central nervous system 
CRF 
Case report form 
CRISPR-Cas9 
Clustered regularly interspaced short palindromic repeats and CRISPR-associated 
protein 9 
CRO 
Contract research organization 
CRU 
Clinical research unit 
CSF 
Cerebrospinal fluid 
CV 
Coefficient of variation 
CYP 
Cytochrome P450  
DBP 
Diastolic blood pressure 
DLT 
Dose-limiting toxicity 
ECG 
Electrocardiogram 
eGFR 
Estimated glomerular filtration rate 
EOS 
End-of-study 


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Abbreviation 
Definition or Explanation 
FDA 
Food and Drug Administration (of the US) 
FSH 
Follicle-stimulating hormone 
Gal 
Galactose 
gal-NAc 
N-acetylgalactosamine 
GALE 
Uridine diphosphate galactose 4’-epimerase 
GALK 
Galactokinase  
GalNet 
International Galactosemia Network 
GALT 
Galactose-1-phosphate uridyltransferase  
GCP 
Good Clinical Practice 
Glc 
Glucose 
glc-1P 
Glucose-1-phosphate 
glc-NAc 
N-acetylglucosamine 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
HED 
Human equivalent dose 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
I/E 
Inclusion/exclusion 
IEC 
Independent Ethics Committee 
IPD 
Important protocol deviation 
IQ 
Intelligence quotient 
IRB 
Institutional Review Board 
IUD 
Intrauterine device 
IVRS/IWRS 
Interactive Voice/Web Randomization System 
LAR 
Legally authorized representative 
LDH 
Lactate dehydrogenase 
LV 
Left ventricular 
MAD 
Multiple ascending dose 
Max 
Maximum 
MDRD 
Modification of Diet in Renal Disease study 
MedDRA 
Medical Dictionary for Regulatory Activities 
Min 
Minimum 


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Abbreviation 
Definition or Explanation 
MRI 
Magnetic resonance imaging  
MRSD 
Maximum recommended starting dose 
MTD 
Maximum tolerated dose 
NASH 
Non-alcoholic steatohepatitis 
NOAEL 
No-observed-adverse-effect level 
NOEL 
No-observed-effect level 
OAT 
Organic anion transporter 
OATP 
Organic anion transporting polypeptide 
OMIM 
Online Mendelian Inheritance in Man 
OTC 
Over-the-counter 
PK 
Pharmacokinetic(s) 
POI 
Primary ovarian insufficiency 
PT 
Preferred Term 
QD 
Once daily 
RBC 
Red blood cell 
RDW 
Red cell distribution width 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SBP 
Systolic blood pressure 
SD 
Standard deviation 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SRC 
Safety Review Committee 
T1/2 
Half-life 
TBD 
To be determined 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time of maximum observed concentration 
UDP 
Uridine diphosphate 
US 
United States 
Note: Additional PK-related abbreviations can be found in Section 7.2. 
 


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1. 
INTRODUCTION 
AT-007 is an aldose reductase inhibitor (ARI) that is being developed by Applied Therapeutics 
Inc. (the Sponsor) for the treatment of Classic Galactosemia (CG) and other severe enzyme 
deficiencies resulting in Galactosemia, such as GALK Deficiency.  
There is no previous human experience with AT-007. This study will be conducted in 
compliance with the protocol, Good Clinical Practice (GCP), and all applicable regulatory 
requirements. 
1.1. 
Background 
Galactosemia is a potentially life-threatening condition caused by genetic defects to enzymes 
involved in the metabolism of galactose. The clinical picture evolves in two phases. The first 
acute phase occurs after birth when the dietary intake of breast milk and formulas containing 
lactose produces a galactose toxicity syndrome manifested by hyperbilirubinemia, failure to 
thrive, vomiting, cataract formation, blood coagulation defects, and renal tubule dysfunction. The 
second phase, which results in long term complications of disease, occurs despite dietary 
restriction of galactose, with later development of speech abnormalities, mental retardation, 
neurological ataxias, cataract, and ovarian failure. This has been shown to be due to endogenous 
production of galactose within the body and cant be prevented by dietary restriction. 
1.1.1. 
Galactosemia Types, Treatment, Prevalence, and Symptoms 
Galactosemia is an inborn metabolic disease caused by aberrant metabolism of the sugar 
galactose, a metabolite of lactose (Berry 2000; Augustin 2010). Galactose, the C-4 epimer of 
glucose, cannot be metabolized directly by the glycolytic pathway. Thus, in organisms ranging 
from bacteria to humans, galactose is first converted to UDP-glucose via the sequential actions 
of three enzymes of the evolutionarily conserved Leloir pathway: galactokinase (GALK), 
galactose-1-phosphate uridyltransferase (GALT) and UDP-galactose 4’-epimerase (GALE) 
(Figure 1). Mutations in the genes coding for these enzymes give rise to different types of 
Galactosemia, which in the developed world are usually detected by routine screening of 
newborn infants. 
AT-007 is in clinical development for the treatment of CG, a subtype of Type I Galactosemia 
further described in Section 1.1.2 and Section 1.1.3 and other severe enzyme deficiencies, such 
as GALK deficiency. 


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Figure 1: 
The Leloir Pathway and Alternative Route of Galactose Metabolism 
 
Source: Modified from Daenzer et al, 2016. 
1.1.2. 
GALT Deficiency (Includes Classic Galactosemia)  
GALT deficiency can be classified into three categories based on its residual activity: Classic 
Galactosemia (CG), Clinical Variant Galactosemia, and Duarte Galactosemia. Classic 
Galactosemia patients exhibit severe GALT deficiency with absent or barely detectable 
erythrocyte and hepatic activity, whereas Clinical Variant Galactosemia is associated with 
residual GALT activity in the RBC and/or liver. Duarte Galactosemia is associated with 15% to 
35% GALT activity. The residual or low GALT activity displayed by Clinical Variant and 
Duarte Galactosemia patients is sufficient to metabolize endogenously produced galactose, and 
in some cases minimal external lactose/galactose intake through the diet can be tolerated. Thus, 
Clinical Variant and Duarte Galactosemia patients often do not display the long-term 
complications seen in CG patients, as long as a stringent diet is adhered to. In contrast, patients 
with severe GALT deficiency (CG) display severe long-term complications, despite dietary 
restriction, and require additional therapeutic intervention to prevent these outcomes. 
Type I Galactosemia (GALT deficiency) is the best studied form of the disease. Classic 
Galactosemia (CG) is characterized by severe GALT deficiency/absent or barely detectable 
GALT activity; Clinical Variant Galactosemia is associated with residual GALT activity in the 
RBC and/or liver; and biochemical variant Galactosemia is associated with 15% to 35% GALT 
activity (e.g., Duarte Galactosemia) (Fridovich-Keil et al, 2014). CG occurs with a frequency of 
150,000 live births in the United States and in other multiethnic populations (Pyhtila et al, 2014). 
In the US, this translates to an incidence of approximately 80 infants born with CG every year. 
Individuals with CG have elevated levels of galactose-1-phosphate (gal-1P), galactitol and 
galactonate in tissues, blood and urine. Galactitol and galactonate are products of alternative 
metabolism of excess galactose which accumulates when the Leloir pathway is blocked 


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(Figure 1). Erythrocyte gal-1P levels have been reported to be 20 to 30 times higher than normal, 
and erythrocyte galactitol levels up to 8 times higher than normal (Yager et al, 2003). Galactitol 
is not detectable in the plasma of healthy controls but is present in the plasma of treated 
individuals with CG at 10 to 12 µmol/L on average, and urinary galactitol can be ≥10-fold higher 
than in normal subjects (Palmieri et al, 1999). Galactitol levels in the brain have also been shown 
to be elevated in CG patients via magnetic resonance imaging (MRI). 
CG typically presents in the neonatal period, with symptoms of poor feeding and poor growth, 
jaundice, liver enlargement and dysfunction, lethargy, hypotonia, renal tubular disease, cataracts 
and E. coli sepsis (Berry 2000). In the newborn period, CG is life-threatening but early 
implementation of a galactose-restricted diet, within the first 10 to 14 days of life, typically 
resolves the acute neonatal complications, and infants appear normal until 1 to 2 years of age, 
when long-term complications begin to emerge (Berry 1997, Demirbas 2018).  
Despite early diagnosis/implementation of a galactose-restricted diet, the majority of patients 
with CG still develop long-term complications. Such chronic complications include CNS-related 
abnormalities (below average IQ [72%], tremor [46%], ataxia [15%], dysarthria [24%], speech 
and language deficiency [88%], depression [39%], anxiety [67%]); low bone density (24%); 
presenile cataracts (>21%); growth delay; and, in almost all females, primary ovarian 
insufficiency (POI) (Berry et al, 2018; Weisbren et al, 2012). It is unclear whether the CNS 
impairment is progressive throughout life, as there is a lack of well-controlled longitudinal 
assessments; however, a negative correlation has been demonstrated between age and cognition, 
suggesting the disease may be progressive through adulthood. 
CNS dysfunction seen in Galactosemia patients appears to be due to broad structural and 
functional abnormalities, which may be the result of diffuse substrate or metabolite deposition 
within the brain. Brain imaging studies have shown cerebral and cerebellar atrophy as well as 
white matter abnormalities, including increased neurite dispersion and lower neurite density. 
Grey matter abnormalities have also been detected using voxel based morphometry. Functional 
MRI has shown altered neural activity and connectivity within several regions of the brain.   
1.1.3. 
GALK Deficiency 
Type II Galactosemia (GALK Deficiency or GALKD) displays wide variation in incidence due 
to three distinct founder mutations, in the Romani population (common in Eastern Europe, 
Ireland and the UK), Costa Rican population, and Japanese population. General incidence in 
Europe is approximately 1:50,000, but incidence in Germany was recently reported to be 
1:40,000 due to an increased population of those of Romani descent. Incidence in the US 
population has not been well studied, but it is estimated to be 1:100,000. Patients with GALK 
deficiency cannot convert galactose into gal-1P and thus do not have elevated levels of this 
metabolite of galactose. Instead, they exhibit elevated levels of galactitol and galactonate. The 
typical presentation is neonatal cataracts (Hennermann et al, 2011), although cases of 
pseudotumor cerebri in the neonatal period have been also described, believed to be due to 
increased intracranial pressure caused by elevated galactitol levels in the brain (Bosch et al, 
2002).  
Until recently, long-term complications, specifically CNS complications (microcephaly, low 
intelligence, and speech and motor difficulties) such as those seen in GALT deficiency were not 
considered features of GALKD. However, a detailed analysis of a GALKD cohort of the Bosnian 


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population that had immigrated to Germany revealed high rates of intellectual deficits, 
microcephaly, and failure to thrive, even in those patients with good compliance on a galactose-
restricted diet. Rates of these CNS complications were similar to those seen in GALT deficiency. 
Because GALKD patients display elevated galactitol levels, but not gal-1P (which does not form 
in GALKD patients), this study supported the strong likelihood that galactitol, not gal-1P, may 
be responsible for CNS complications seen in Galactosemia patients (Hennermann, 2011). 
1.1.4. 
Enzyme Defects and Mechanisms of Disease 
It was long hypothesized that accumulation of gal-1P was responsible for the CNS complications 
and ovarian insufficiency observed in patients with GALT deficiency (Type I Galactosemia) 
because patients with GALK deficiency (Type II Galactosemia), who do not produce or 
accumulate gal-1P, were thought to be free of such complications. However, a study of GALK 
deficiency in a cohort of a Bosnian population that had immigrated to Germany (Hennermann, 
2011), revealed high rates of CNS dysfunction and developmental deficiencies similar to those 
seen in GALT-deficient patients. GALK-deficient patients did not have elevated gal-1P, either 
before or after implementation of a galactose-restricted diet, but did demonstrate highly elevated 
levels of galactitol. On a galactose-restricted diet, GALKD patients’ galactose levels largely 
normalized, but galactitol levels remained elevated by about 10-fold compared with healthy 
control values. This study was the first prospective study of GALK-deficient patients identified 
via newborn screening. Before this study, these patients had been found primarily in countries 
where newborn screening and careful evaluations of Galactosemia outcomes were not performed 
(e.g., Bosnia and Bulgaria). This new information provided by the German GALKD patient 
cohort suggested that galactitol (not gal-1P) is the metabolite responsible for CNS complications 
in patients with Galactosemia. 
Several other clinical findings support the role of galactitol (either in addition to gal-1P or 
instead of gal-1P) in long-term complications in patients with GALT and GALK deficiencies. 
For example, little correlation has been found in Galactosemia patients between the levels of 
gal-1P and clinical manifestations (Pyhtila et al, 2014). In addition, galactitol accumulation in the 
brain (detected by in vivo brain MRI with spectroscopy) has been reported to cause cerebral 
edema (Martineli et al, 2016), encephalopathy (Berry et al, 2001), and delay of psychomotor 
development with bilateral ocular cataracts (Otaduy et al, 2006). A restricted lactose-free diet 
induced almost complete resolution of the MRI white matter signal intensity abnormalities and 
disappearance of the galactitol peaks (Otaduy et al, 2006). 
Experimental results detailed below provide additional evidence against gal-1p (or gal-1p alone) 
and/or point toward galactitol as a critical factor in the pathogenesis of the delayed and/or 
long-term complications of Galactosemia such as CNS disturbances and possibly ovarian 
insufficiency later in life: 
• AR inhibition was shown to prevent galactose-induced ovarian dysfunction in the 
Sprague-Dawley rat (Meyer et al, 1992). 
• A model of CG in Drosophila melanogaster, whose genome contains sequences 
related to all three Leloir pathway genes, mimics aspects of both the acute (survival 
of larvae) and long-term (climbing ability of adult males and fecundity of females) 
outcomes of CG (Daenzer et al, 2016). Like human patients, and unlike mice, 
GALT-deficient Drosophila larvae exhibit galactose-dependent lethality, which can 


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be rescued by the initiation of a galactose-restricted diet early in development or by 
the expression of a human GALT transgene. GALT-deficient flies that are raised and 
maintained exclusively on a galactose-restricted diet still demonstrate a clear 
deficiency in the normal negative geotaxic response seen in controls. As with the 
acute galactose-dependent phenotype, this delayed, galactose-independent muscular 
or neuromuscular deficit is rescued by the expression of a human GALT transgene. In 
this model, as expected, loss of GALK lowered or eliminated gal-1P accumulation in 
GALT-null animals. However, there was no concomitant rescue of larval survival or 
adult climbing or fecundity phenotypes. These findings strongly contradict the 
long-standing hypothesis that gal-1P accumulation underlies the pathophysiology of 
acute and long-term outcomes in GALT-null Drosophila and suggests that other 
metabolite(s) of galactose are responsible for the phenotype. 
• Another model of CG, the GALT-null Sprague-Dawley rat model was created by 
using CRISPR-Cas9 gene editing technology [J. Fridovich-Keil, PhD, personal 
communication]. The GALT-null animals are homozygous for M3, a small frameshift 
insertion designated as rGALTm3. All M3/M3 neonates demonstrate complete 
absence of GALT activity in all tissues tested with apparently normal levels of the 
other Leloir enzymes, GALK and GALE. Like human patients with CG, following 
exposure to galactose, M3/M3 rats demonstrate abnormal accumulation of galactose, 
galactitol, galactonate, and gal-1P. All homozygotes also demonstrate conspicuous 
bilateral cataracts that are not seen in heterozygotes or wild- type animals. In contrast 
to human patients with CG, the GALT-null rats do not exhibit the lethal neonatal 
symptoms following exposure to mothers’ milk (possibly because rat breast milk 
contains 10% of the lactose content of human breast milk), but they do demonstrate, 
in addition to cataracts, mild growth restriction both before and after weaning and a 
variety of CNS deficits as adults. These deficits can be revealed by tests including the 
rotarod (tests balance and coordination), Morris Water Maze (tests memory and 
cognitive flexibility), and Novel Object Recognition tests. 
1.1.5. 
Clinical Management of Galactosemia 
Currently, there are no therapies available for treatment of Galactosemia or prevention of the 
long-term complications associated with severe deficiencies in GALT or GALK. Standard of 
care is immediate implementation of a life-long galactose-restricted diet. Although the diet can 
reverse the acute clinical picture in the newborn and in many cases prevent fatalities in newborns 
if initiated early enough, it does not prevent the appearance of long-term complications in 
patients with severe enzyme deficiencies. 
Guidelines recommend that children with severe GALT or GALK deficiencies be screened for 
speech and language delay, hearing and cognitive disorders at ages 7 to 12 months, and at 2, 3, 
and 5 years. Interventions include intensive therapy by a speech expert, psychologist, 
developmental pediatrician, etc. Also recommended are regular neurological and psychosocial 
evaluations, bone density and ophthalmologic assessments, a comprehensive dietary evaluation 
including monitoring of calcium intake, vitamins D and K supplementation if necessary, 
hormonal status evaluation and hormone replacement therapy consideration, as well as a regular 
exercise and assessment of skeletal problems. Periodic assessment of galactose metabolites in 
erythrocytes can help clinicians confirm dietary compliance (Welling et al, 2017). 


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Despite dietary restriction, patients with severe enzyme deficiencies still present with significant 
long-term complications of disease. Most adults with Galactosemia have an IQ under 85 and live 
at home with their parents or in a care facility. Because there are not many patients with 
Galactosemia over the age of 40 years old (because most died at birth prior to the initiation of 
newborn screening), the long-term prognosis of adults with Galactosemia is unclear. 
Complications of disease that present in adulthood, such as tremor and seizures, have not been 
studied prospectively in adults, nor has progression of cognitive impairment and IQ. 
1.1.6. 
Galactosemia Prevalence 
Prior to the initiation of newborn screening, which began in the US in the 1960s and was 
mandatory in all 50 States in 2004, nearly all infants with CG died at birth due to acute exposure 
to lactose. The current living population of CG patients in the US is estimated to be 
approximately 2,800 individuals. This is based on cumulative newborn screening results 
identifying 2,500 patients in the US from initiation of screening through 2014, and a yearly birth 
rate of approximately 80 patients per year in the US (providing an additional estimated 
240 births in 2014 through 2018). The GALK-deficient Galactosemia population is largely 
undetermined in the US, but is estimated to be significantly lower than the CG population, based 
on an extremely low incidence in the US ethnic population.   
1.2. 
Development of Aldose Reductase Inhibitors (ARIs) 
If accumulation of galactitol is responsible for the long-term complications of Galactosemia, 
then it stands to reason that blocking AR from converting galactose to galactitol, in combination 
with a galactose-restricted diet, may be able to prevent/reduce these Galactosemia complications.  
Applied Therapeutics Inc. (the Sponsor) is currently developing two structurally similar ARIs: 
one ARI is designated as AT-001 and another one is designated as AT-007. AT-001 is not CNS 
penetrant, while AT-007 penetrates the CNS when administered orally. 
Using a genetic rat model of Galactosemia (“GALT null”), the Sponsor has successfully 
recapitulated critical features of Type I Galactosemia seen in humans. The accumulation of 
galactitol in various parenchyma and the onset of cataracts in this animal model can serve as 
biochemical and clinical markers of disease and disease progression. 
In a pilot study in GALT-null neonatal rats, AT-001 (or placebo) was administered orally, 
suspended in the liquid formula, starting on the day after they were born and continuing for 9 to 
18 days. Treatment with AT-001 decreased galactitol levels in the liver and brain and reduced or 
prevented the development of cataracts. 
The Sponsor decided to develop AT-007 for the treatment of CG because it is both CNS 
penetrant and retinally penetrant. In the same “GALT null” rat model, treatment with AT-007 
was able to normalize biochemical markers of Galactosemia and prevented the onset of cataracts, 
but importantly also prevented and CNS dysfunction.   
This protocol (Study AT-007-1001) is the first-in-human study for AT-007. 
1.3. 
Choice of Study Population 
Study AT-007-1001 is being conducted in healthy adult subjects (Parts A [single ascending dose 
or SAD] and B and C [multiple ascending dose or MAD]); adult subjects with CG (Part D [SAD, 


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MAD] and Part D Extension); and adult subjects with GALK-deficient Galactosemia (Part E 
[SAD and MAD]). 
1.4. 
Dose Rationale 
The initial first-in-human dose for Part A (SAD) was 0.5 mg/kg. This did not exceed the 
maximum recommended starting dose (MRSD) using a safety factor of 10.  
The MRSD is based on the 13-week rat and dog Good Laboratory Practice (GLP) studies 
evaluating doses of 50, 200, and 1000 mg/kg/day in rats and 50, 200, and 400 mg/kg/day in dogs.  
AT-007 was administered to Beagle dogs once daily (QD) for at least 91 consecutive days via 
oral gavage. The following parameters and endpoints were evaluated in this study: clinical signs, 
body weights, body weight gains, food consumption, ophthalmology, electrocardiography, 
clinical pathology parameters (hematology, coagulation, serum chemistry, and urinalysis), 
toxicokinetic parameters, gross necropsy findings, organ weights, and histopathologic 
examinations.  
There were no test article-related changes for ophthalmology, electrocardiography, clinical 
pathology, or organ weight data throughout the study.  
Administration of AT-007 by once daily oral gavage was well tolerated in dogs at levels of 
50, 200, and 400 mg/kg/day. The early termination (Day 85) in 1 male dog from the 
400 mg/kg/day was associated with hematopoietic changes that were not observed in any other 
male or female dog at any dose level; as such, this observation was considered sporadic and a 
relationship with the test-article could not be established. 
Therefore, the no-observed-adverse-effect level (NOAEL) was considered to be 400 mg/kg/day. 
This dosage corresponded to mean AUC0-24 values of 1,130,000 and 1,160,000 h*ng/mL on 
Day 91 for males and females, respectively, and Cmax values of AT-007 of 145,000 and 
155,000 ng/mL on Day 91 for males and females, respectively  
In the 13-week rat toxicology study, doses of 50, 200, and 1000 mg/kg/day were administered 
QD for 91 consecutive days via oral gavage. The following parameters and endpoints were 
evaluated in this study: clinical signs, body weights, body weight gains, food consumption, 
ophthalmology, clinical pathology parameters (hematology, coagulation, clinical chemistry, and 
urinalysis), toxicokinetic parameters, gross necropsy findings, organ weights, and 
histopathologic examinations. 
There were no control or  test article-related clinical observations or significant effects on body 
weights, food consumption, ophthalmology, clinical pathology, or mortality findings throughout 
the study. All gross necropsy and histopathological findings for the main and recovery periods 
resulted in no evidence of test article-related effects. Therefore, the NOAEL in the rat was 
considered to be 1000 mg/kg/day. This dosage corresponded to mean AUC0-24 values of 
2,040,000 and 2,360,000 h*ng/mL on Day 90 for males and females, respectively, and Cmax 
values of AT-007 of 182,000 and 306,000 ng/mL on Day 90 for males and females, respectively. 
Based on the NOAEL of 1000 mg/kg in rats and the NOAEL of 400 mg/kg in dogs, the human 
equivalent doses (HEDs) were calculated to be the following: 160 mg/kg/day from the rat and 
216 mg/kg/day from the dog. Because the NOAEL of 400 mg/kg/day in dogs is the lower of the 
two, the HED of 216 mg/kg/day was chosen for the derivation of the MRSD. Therefore, using 


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the default safety factor of 10, the MRSD for AT-007 is 21.6 mg/kg/day. After consideration of 
other factors related to known pharmacology and another significant clinical program in the 
same mechanistic class, the starting dose for AT-007 in Part A was 0.5 mg/kg/day. This equates 
to a safety margin of 432 (216/0.5). 
Dose levels in Part A escalated from 0.5 mg/kg to 5 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg 
in the 5 cohorts (Cohorts A1 through A5) with no dose-limiting toxicity (DLT) identified in any 
cohort. 
The first 3 cohorts in Part B (Cohorts B1, B2, and B3) escalated from 5 mg/kg to 10 mg/kg to 
20 mg/kg following acceptable results for the same doses in Part A. Cohort B4 will start with this 
version of the protocol (version 5.0) and use a dose of 40 mg/kg based on that dose being 
acceptable in Cohort A5. The study drug exposure results were carefully considered to ensure 
that the plasma concentrations measured in Part A were in the range to detect changes in AR 
activity and galactitol levels in subjects with CG.  
The doses in Part C are based on those in Part B. Cohort C1 was conducted with the same dose 
as Cohort B2 (10 mg/kg). Cohort C2 used the dose as Cohort B3 (20 mg/kg). Cohort C3 will use 
the same dose as Cohort B4 (40 mg/kg). 
The initial dose in Part D (5 mg/kg) was based on data from Part A (Cohorts A1 through A4) and 
Part B (first 2 cohorts). 
The starting dose in Part E will be the most clinically appropriate dose as determined by the 
evaluation of safety, tolerability, and PD (reduction in galactitol level) in Part D. The dose will 
not be higher than the highest acceptable dose in Part D at the time of starting Part E (after all 
subjects complete Cohorts D1 and D2 but may be before, during, or after Cohort D3). 
The dose for the first cohort of the Part D Extension (Cohort DE1) will be 20 mg/kg/day based 
on acceptable SAD and MAD safety and PK data from Cohort D2.  
AT-007 dose levels in Part A ranged from 0.5 and 40 mg/kg/day. Dose levels in subsequent parts 
of the study are based on the safety and PK results (and galactitol results in Parts D, E, and D 
Extension only) of previous cohorts and/or previous parts of the study. Doses higher than 
40 mg/kg may be evaluated if the human Cmax and AUC are substantially lower than the 
corresponding values calculated in nonclinical experiments and no DLT is observed up to and 
including at the 40 mg/kg dose. If dose escalation above 40 mg/kg is feasible based on the above 
criteria, these higher doses may be investigated in additional SAD and MAD cohorts in healthy 
subjects and in subjects with Galactosemia if no AT-007 levels are detected in the cerebrospinal 
fluid (CSF) collected from the healthy subjects enrolled in Cohort C3. 
Although it is anticipated that daily doses do not need to be higher than 40 mg/kg, there is a 
chance that the PK data observed during the study will show otherwise. If this happens, then 
additional subjects may be enrolled. 


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2. 
OBJECTIVES AND ENDPOINTS 
The primary objective of this multicenter, first-in-human study is the following: 
• To evaluate the safety of single and multiple ascending doses of orally administered 
AT-007 in healthy adult subjects and adult subjects with CG or GALK-deficient 
Galactosemia 
The secondary objectives of this study are the following: 
• To evaluate the pharmacokinetic (PK) parameters of single and multiple doses of 
orally administered AT-007 in healthy adult subjects and adult subjects with CG or 
GALK-deficient Galactosemia 
• To evaluate the effect of single and multiple doses of orally administered AT-007 on 
the level of galactitol, a biomarker of AR activity, in adult subjects with CG or 
GALK-deficient Galactosemia 
• To evaluate the effect of single and multiple doses of orally administered AT-007 on 
the levels of galactose and its other metabolites in adult subjects with CG or 
GALK-deficient Galactosemia 
The exploratory objectives are the following: 
• To measure the levels of AT-007 in the cerebrospinal fluid (CSF) of healthy adult 
subjects  
 
The primary endpoints of this study are overall safety and adverse events (AEs). Safety will be 
assessed by the following: 
• AEs 
• Clinical safety laboratory tests (hematology, chemistry, urinalysis) 
• Physical examinations 
• Vital signs 
• Electrocardiograms (ECGs) 
The secondary endpoints are the following: 
• PK parameters (Section 7.2) in healthy subjects, subjects with CG, and subjects with 
GALK-deficient Galactosemia 
• Galactose, galactitol, and other galactose metabolites in the blood of subjects with CG 
and subjects with GALK-deficient Galactosemia 
• Urine galactitol for subjects with CG and subjects with GALK-deficient 
Galactosemia 
The exploratory endpoints are the following: 
• AT-007 level in the CSF of healthy subjects (Part C only) 
PK samples will be stored for possible future analysis of AT-007 metabolites. 


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3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design 
This is a first-in-human, randomized, placebo-controlled, 6-Part, SAD and MAD study in healthy 
adult subjects, adult subjects with CG, and adult subjects with GALK-deficient Galactosemia. 
The study will assess the safety and PK of AT-007 in these subjects as well as the effect of 
AT-007 on biomarkers of galactose metabolism (galactose and galactose metabolites) in subjects 
with galactosemia. The study is being conducted in multiple centers in the US and Europe. This 
study consists of 6 parts (Table 1) with the timing of the parts as shown in Figure 2.  
Table 1: 
Study Design 
Study 
Part 
 
Study Population 
 
Design 
Planned 
Number 
of 
Cohorts 
Subjects Per 
Cohort 
Total # 
of 
Subjects 
Part A 
Healthy Adult Subjects 
SAD 
5 
8 
40 
Part B 
Healthy Adult Subjects 
MAD (QD for 7 days) 
4 
6 in 2 cohorts & 8 
in 2 cohorts 
28 
Part C 
Healthy Adult Subjects 
MAD (QD for 7 days) 
3 
4 
12 
Part D 
Adult Subjects with CG 
SAD, 5-day washout, 
MAD (QD for 27 days) 
3 
6 
18 
Part E 
Adult Subjects with 
GALK-deficient 
Galactosemia 
SAD, 5-day washout, 
MAD (QD for 27 days) 
1 to 3 
6 
18 
Part D 
Extension 
Adult Subjects with CG 
MAD (QD for 90 Days) 
1 to 2 
8 to 28 
28 
CG = Classic Galactosemia; EOS = end of study; MAD = multiple ascending dose; QD = once daily 
(dosing); SAD = single ascending dose; TEAE = treatment emergent adverse event. 
The total number of subjects column reflects the maximum number of subjects if all cohorts are 
conducted with the planned number of subjects and no subject participates in more than 1 cohort and/or 
part. However, in Parts D and E, subjects are allowed to participate in multiple cohorts (assuming no 
safety or tolerability issues in the prior cohort) on any treatment assignment with a ≥ 5-day washout 
period between the last dose of study drug in one cohort and the first dose of study drug in the next 
cohort. Also, Part D subjects can participate in Part D Extension at any time after the Part D EOS Visit 
(Part D completers and those who discontinued for any reason other than study drug related TEAE and 
had an EOS Visit more than 14 days after the last dose) or any time beyond 14 days after the last dose in 
Part D (Part D subjects who discontinued Part D for any reason other than study drug related TEAE and 
did not have an EOS Visit more than 14 days after the last dose). 
Parts A and B are double-blind. Part C is open-label. In Parts D, E, and D Extension, the clinical site staff 
(except for the unblinded pharmacist) and the subjects are blinded to study treatment but the Sponsor is 
not blinded.  
The number of cohorts and total number of subjects may increase if doses > 40 mg/kg are tested in 
additional cohorts (see Section 1.4). Also, in Parts D and E, the overall number of subjects per cohort 
may be increased up to 8 subjects to address any potential lost-to-follow-up among subjects treated with 
either placebo or AT-007. Up to 28 total subjects in up to 2 cohorts are planned for Part D Extension. 


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Figure 2: 
Study Schematic 
 
Within each Part, the Cohorts are sequential. Solid lines with arrows indicate that data from the part or cohort at the 
non-arrow end are required before the part or cohort at the arrow end can start. Dotted lines indicate cohorts (C1 and 
B3; C3 and B4) that will be conducted simultaneously. Parts D, E, and D Extension are not dependent on Part C 
results, and no temporal relationship between Parts D, E, and D Extension and Part C is implied. Also, with the 
exception of Cohorts B4, C3, D3, E2, E3, and DE2 being directly or indirectly dependent on Cohort A5 results, no 
temporal relationship between Cohort A5 and any other part/cohort is implied. Cohort DE2 (start and dose level) are 
not dependent on results from Cohort DE1. Figure is not to scale. 
Parts A, B, and C are being conducted in a single clinical research unit (CRU) in the US. 
Subjects within each cohort in Part A were enrolled and dosed at approximately the same time 
(within 2 to 3 days for the first cohort and on the same day for the subsequent cohorts). Subjects 
within each cohort in Part B will be enrolled and dosed on the same days. The first cohort of 
Part C (C1) was conducted simultaneously with the third cohort of Part B (B3) and received the 
same dose (10 mg/kg) as the second cohort of Part B (B2). The second cohort of Part C (C2) 
started after all subjects in the third cohort of Part B (B3) completed the study (minus the End-
of-Study [EOS] Visit) and received the same dose (20 mg/kg) as Cohort B3; safety and PK 
results for Cohort C1 were also considered before starting Cohort C2. The third cohort in Part C 
(C3) will be conducted simultaneously with the fourth cohort of Part B (B4) and receive the 
same dose (40 mg/kg); safety and PK results for Cohort C2 were also considered before starting 
Cohort C3. For Cohorts B3 and C1, subjects were enrolled and dosed on the same day but in 
different parts of the CRU to separate double-blind (B3) from open-label (C1) dosing. All 
subjects in Cohort C2 were enrolled and dosed on the same day. All subjects in Cohorts B4 and 
C3 will be enrolled and dosed on the same day but in different parts of the CRU to separate 
double-blind (B4) from open-label (C3) dosing. 
Parts D, E, and D Extension are being conducted in multiple CRUs. It is not anticipated that 
subjects within each cohort will be enrolled/dosed at approximately the same time.  


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Initially, 4 double-blind dosing cohorts were planned in the SAD portion of the study in healthy 
subjects (Part A); subsequently, a fifth cohort (A5) was added to Part A. Within each cohort of 
8 subjects, 6 subjects were randomly assigned to AT-007 and 2 subjects were randomly assigned 
to placebo. For the first cohort, the first 2 subjects were sentinel subjects with 1 subject randomly 
assigned to AT-007 and 1 subject randomly assigned to placebo. These 2 sentinel subjects were 
observed for at least 24 hours before any of the additional subjects (6 subjects: 5 randomly 
assigned to AT-007 and 1 randomly assigned to placebo) in the first cohort were dosed. The dose 
levels of AT-007 for Cohorts A1, A2, A3, A4, and A5 were 0.5, 5, 10, 20, and 40 mg/kg. 
Before the study proceeded to Part B (MAD in healthy subjects), safety data from Cohorts A1 
through A4 in Part A (SAD in healthy subjects) were evaluated by the Safety Review Committee 
(SRC) (Section 3.4) and all PK data from Cohorts A1 through A4 were evaluated by the 
Sponsor. As of this protocol version, Cohorts A1 through A5 (0.5, 5, 10, 20, and 40 mg/kg) have 
completed the study with acceptable results. 
Four double-blind dosing cohorts are planned in the MAD portion of the study in healthy 
subjects (Part B). Within each cohort of 6 or 8 subjects, 4 or 6 subjects will be randomly 
assigned to AT-007 and the remaining 2 subjects will be randomly assigned to placebo. Subjects 
will receive study drug (AT-007 or placebo) QD for 7 consecutive days. The starting dose level 
of AT-007 for the first cohort (B1) was 5 mg/kg based on the results of Part A. Subsequent 
cohorts (B2 and B3) were given 10 and 20 mg/kg based on results from the previous cohorts in 
both Parts A and B. Cohort B4 is planned with a dose level of 40 mg/kg based on data from 
Cohort A5. 
The review of the PK data from Cohorts A1 through A4 and the first 2 cohorts of Part B 
confirmed that once daily (QD) dosing is adequate.  
Part C consists of 3 open-label MAD dosing cohorts (same dose levels as Cohorts B2, B3, and 
B4) in healthy subjects. Cohort C1 was conducted at the same time as Cohort B3 using the same 
dose (10 mg/kg) as Cohort B2. Cohort C2 was conducted after all subjects in Cohort B3 
completed the study (minus the EOS Visit) and used the same dose (20 mg/kg) as Cohort B3; 
data from Cohort C1 were also considered before starting Cohort C2. Cohort C3 will run 
concurrently with Cohort B4 and use the same dose (40 mg/kg); data from Cohort C2 were also 
considered before starting Cohort C3. Within each Part C cohort, all 4 subjects will be treated 
with AT-007. Subjects will have a lumbar puncture on Day 7 to collect CSF for the measurement 
of AT-007 with the exact timing of the lumbar puncture based on PK data from Part B. 
Otherwise, the subjects in Part C have the same schedule as the subjects in Part B (minus 
randomization).  
Before the study proceeded to Part D (SAD and MAD in subjects with CG), safety data from 
Cohorts A1 through A4 in Part A and the first 2 cohorts in Part B were evaluated by the SRC and 
all PK data from these cohorts were evaluated by the Sponsor. 
Three dosing cohorts are planned for subjects with CG (Part D). The same subjects will receive 
both the single dose and the multiple doses. Within each cohort of 6 subjects, 4 subjects will be 
randomly assigned to AT-007 and 2 subjects will be randomly assigned to placebo. Following a 
single dose of study drug (AT-007 or placebo), there will be a 5-day washout. Subjects who 
tolerate the single-dose will receive 1 daily dose of the same study drug (AT-007 or placebo) for 
27 consecutive days. The decision of whether each individual subject can start multiple dosing 


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will be made by the Investigator in consultation with the Sponsor. No subject in Part D can 
start multiple dosing without explicit agreement from the Sponsor. Subjects will complete 
the 27 days of treatment and the associated PK, PD, and safety assessments through the 2 days 
after the MAD portion and then have an EOS Visit at 28 days after the last dose. 
The starting dose for Part D (i.e., for Cohort D1) was based on results from Part A (Cohorts A1 
through A4) and Cohorts B1 and B2 and at 5 mg/kg was lower than the dose for Cohort B2 
(10 mg/kg). The dose for Cohort D2 (20 mg/kg) was based on results from these cohorts plus 
Cohorts B3 and D1; results for Cohort C1 were also considered. The dose for Cohort D3 will be 
based on results from all cohorts in Parts A and B and Cohorts D1 and D2 and will not be higher 
than the dose for Cohort B4.  
Before the study proceeds to Part E (SAD and MAD in subjects with GALK-deficient 
Galactosemia), safety data from all completed cohorts in Parts A, B, and D of the study will be 
evaluated by the SRC and all PK data from these cohorts will be evaluated by the Sponsor. The 
starting dose for Part E will not be higher than the highest acceptable dose in Part D at the time 
of starting Part E (after all subjects complete Cohorts D1 and D2 but may be before, during, or 
after Cohort D3). The dose for subsequent cohorts (if any) in Part E will be based on results from 
the previous cohort(s) in Part E. 
One to 3 dosing cohort are planned for subjects with GALK-deficient Galactosemia (Part E). The 
same subjects will receive both the single dose and the multiple doses. Within each cohort of 
6 subjects, 4 subjects will be randomly assigned to AT-007 and 2 subjects will be randomly 
assigned to placebo. Following a single dose of study drug (AT-007 or placebo), there will be a 
5-day washout. Subjects who tolerate the single-dose will receive 1 daily dose of the same study 
drug (AT-007 or placebo) for 27 consecutive days. The decision of whether each individual 
subject can start multiple dosing will be made by the Investigator in consultation with the 
Sponsor. No subject in Part E can start multiple dosing without explicit agreement from the 
Sponsor. Subjects will complete the 27 days of treatment and the associated PK, PD, and safety 
assessments through the 2 days after the MAD portion and then have an EOS Visit at 28 days 
after the last dose. 
Notes for Parts D and E: The overall number of subjects per cohort may be increased up to 
8 subjects to address any potential lost-to-follow-up among subjects treated with either placebo 
or AT-007. Subjects treated with study drug (placebo or AT-007) in a cohort may be randomized 
to treatment in another cohort (separate consent required) within the same Part (assuming no 
safety or tolerability issues in the prior cohort) as long as there is a washout period of ≥5 days 
between the last dose in a cohort and the first dose in the next cohort.  
The dose for the first cohort of the Part D Extension (DE1) will be 20 mg/kg/day based on 
acceptable SAD and MAD safety and PK data from Cohort D2. After SRC review of all SAD 
and MAD data and Sponsor review of PK and galactitol data for Cohorts D1 through D3, a 
second cohort of the Part D Extension (DE2) may be initiated to evaluate a dose >20 mg/kg/day 
if this dose was well tolerated in the SAD and MAD portions of the study in both healthy 
volunteers and subjects with CG. 
In Part D Extension, within each cohort of up to 28 subjects, subjects will be randomly assigned 
in a 3:1 to AT-007 and placebo. Subjects will receive 1 daily dose of the same study drug 
(AT-007 or placebo) for 90 consecutive days. Subjects will complete the 90 days of treatment 


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and the associated PK, PD, and safety assessments through the day after the last dose and then 
have an EOE Visit at 28 days after the last dose. The EOE Visit will not be required for subjects 
who transition to a separate Open-Label Extenstion Study. For these subjects the study 
completion will be the completion of the Treatment Period at Day 91.  
For all its parts (A, B, C, D, E, and D Extension), the study consists of a Screening Period 
(28 days [Day -28 to Day -1] in Parts A, B, and C; 40 days [Day -40 to Day -1] in Parts D and E; 
and Day -60 to Day -1 in Part D Extension for de novo subjects who did not participate in Part D 
and subjects whose last visit in Part D was >60 days before Day 1 in the Part D Extension]), a 
period of study treatment and associated assessments, and an EOS Visit (28 days after the last 
dose of study drug) (for Part D Extension, the visit at 28 days after the last dose is called the end 
of extension [EOE] Visit). Part D Extension de novo subjects may also participate in optional 
prescreening. Subjects will be randomized and receive the first dose of study drug on Day 1. At a 
minimum, subjects will remain at the clinical research unit (CRU) through 24 hours after the first 
dose. Subjects in Part A will have 1 in-clinic stay during the Treatment Period with the single 
dose taken in the CRU. Subjects in Parts B and C will have 1 in-clinic stay with all 7 doses taken 
in the CRU. Subjects in Parts D and E will have 3 in-clinic stays with most doses taken at home. 
Subjects in Part D Extension will have 2 in-clinic stays and monthly visits (home health or in-
clinic) with most doses taken at home. Subjects who withdraw or are withdrawn from the study 
after taking study drug will not be replaced.  
The Schedules of Assessments for Parts A, B, C, D, E, and D Extension are provided in 
Appendix A (Part A), Appendix B (Part B), Appendix C (Part C), Appendix D (Part D), 
Appendix E (Part E), and Appendix F (Part D Extension), respectively.  
At selected time points during all parts of the study, all subjects will have the following: 
• Assessment of AEs 
• Blood and urine samples collected for routine safety laboratory assessments 
• Physical examinations, assessment of vital signs, and ECGs 
• Pregnancy tests (all females at screening and females of childbearing potential 
subsequently) 
• Blood samples collected for PK 
For subjects enrolled in selected cohorts in Parts A and D (Cohorts A4, A5, and D3), urine 
samples will be collected at selected time points after the single dose for the assessment of 
AT-007.  
Subjects in Part C will have a lumbar puncture on Day 7 after the last dose to collect CSF for 
measurement of AT-007. The timing of the lumbar puncture relative to the last dose will be 
based on the PK data from completed cohorts in Part B. The intent is for the lumbar puncture to 
be taken close to the time of the maximum observed concentration (Tmax) of AT-007 after the last 
dose. 
During Part D, at selected time points, subjects will have blood samples taken for the assessment 
of GALT activity in red blood cells, GALT gene analysis, and aldose reductase activity; these 
assessments will also be done for Part D Extension subjects who did not participate in Part D but 
will not be repeated for those who did participate in Part D. Also, subjects in both Part D and 


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Part D Extension will have blood samples taken for the assessment of galactose and its 
metabolites, and subjects in Part D will also have urine collected for the assessment of galactitol.  
During Part E, at selected time points, subjects will have blood samples taken for the assessment 
of GALK activity in red blood cells, GALK gene analysis, aldose reductase activity, as well as 
galactose and its metabolites and urine collected for the assessment of galactitol.  
Within each multi-cohort part (A, B, C, and D [and E, if applicable]) of the study, in the 
subsequent cohorts after the first cohort, the dose may be increased, decreased, or repeated. The 
SRC will review safety (including AE, laboratory, physical examination, vital signs, and ECG 
data) through Days 3, 8, 8, 12, and 12 during Parts A, B, C, D, and E, respectively, for each 
cohort and provide a recommendation for the next cohort as needed. If there is a second cohort in 
Part D Extension, the dose will be higher than 20 mg/kg and depend on the results for that dose 
in healthy subjects and subjects with CG in Part D. 
3.2. 
Rationale for Overall Study Design 
The overall study design is commonly used for Phase 1 safety and PK studies. Incorporation of 
sentinel subjects in any cohort, especially the first cohort, is designed to limit the number of 
subjects exposed to a potentially unsafe drug or unsafe dose. The durations of the in-clinic stays 
are based on safety and practical considerations to ensure proper assessment of potential AEs and 
collection of biological samples and various examinations/measurements required by the study. 
An EOS or EOE Visit is conducted at 28 days after the last dose to assess the outcome of AEs (if 
any) after study drug treatment and to ensure proper reporting of AEs with onset during the 
post-treatment period. Use of an SRC to assess safety and PK data before dose escalation and 
before transitioning from single doses (Part A) to multiple doses (Parts B and C) is standard 
practice in such studies. Having safety and PK data in healthy subjects before dosing subjects 
with the proposed indication(s)) (Parts D, E, and D Extension) is also standard practice. Having 
longer duration doses not exceed doses that have been studied for shorter durations is standard 
practice as well. Having the Investigator (with explicit agreement from the Sponsor) rather than 
the SRC decide if safety for the sentinel subjects in Cohort A1 is acceptable and if a subject in 
Part D or E will start multiple dosing with study drug after the single dose are practical 
consideration because the decisions needs to be made within 24 hours (Cohort A1) and within 
the 5-day washout period (individual subjects in Parts D and E). Galactose and its metabolites 
are only measured in subjects with CG or GALK-deficient Galactosemia (Parts D, E, and 
D Extension) because AR (the enzyme inhibited by AT-007) converts galactose to galactitol only 
in the presence of extremely high levels of galactose (found in subjects with CG or GALK-
deficient Galactosemia but not healthy subjects).   
3.3. 
Study Drug Administration Schedules 
Parts A, B, C, and D of the study will start more or less sequentially followed by starting Parts E 
and D Extension more or less concurrently. However, conduct of all study parts will overlap 
(Figure 2 and Section 3.1).  
Within each multi-cohort part, the cohorts (dose levels) will be dosed sequentially. The SRC will 
review available safety data through a pre-specified timeframe (Day 3 for Part A, Day 8 for 
Parts B and C, and Day 12 for Part D [and E, if applicable]) and provide recommendations for 
the next cohort. If there is a second cohort in Part D Extension, the dose will be higher than 


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20 mg/kg and depend on the results for that dose in healthy subjects and subjects with CG in 
Part D. Additional cohorts will be enrolled if it is deemed appropriate after safety assessment by 
the SRC and confirmation by the Sponsor. A decision to repeat a dose level or to study another 
higher or lower dose level may be made. The Investigator(s) and Institutional Review Boards 
(IRBs) / Independent Ethics Committees (IECs) will be notified of these decisions.  
The SRC will also review data for the last cohort for each study part except that there will be no 
next cohort within the same part of the study. 
AT-007 dose levels in Part A were between 0.5 and 40 mg/kg. Dose levels in subsequent parts of 
the study are based on the safety and PK results (and galactitol results in Parts D, E, and E 
Extension only) of previous cohorts and/or previous parts of the study. Doses higher than 
40 mg/kg may be evaluated if the human Cmax and AUC are substantially lower than the 
corresponding values calculated in nonclinical experiments and no dose limiting toxicity is 
observed up to and including at the 40 mg/kg dose. If dose escalation above 40 mg/kg is feasible 
based on the above criteria, these higher doses may be investigated in additional SAD and MAD 
cohorts in healthy subjects and in subjects with CG or GALK-deficient Galactosemia if no 
AT-007 levels are detected in the CSF collected from the healthy subjects enrolled in Cohort C3. 
All doses of study drug (AT-007 or placebo) should be taken in the morning under fasting 
conditions (after at least a 10-hour overnight fast that is broken 2 hours after dosing [mandatory 
for doses with PK sampling time points and recommended for all other doses]). This will be the 
case regardless of whether the study drug dose is taken at the CRU or at home. 
3.3.1. 
Part A: Double-blind Single Ascending Dose (SAD) in Healthy Subjects 
Four dose levels were initially planned for the SAD group and a fifth dose level was recently 
added and completed (Table 2). Subjects were enrolled in 5 sequential cohorts of 8 subjects each, 
for a total of 40 subjects. The initial dose level was 0.5 mg/kg based on nonclinical study results 
(Section 1.4). The first cohort included a sentinel group (first 2 subjects with 1 per treatment) 
dosed at the same time. Dose administration for the remainder of the first cohort occurred only at 
least 24 hours after the 2 sentinel subjects received study drug (AT-007 or placebo) and were 
contingent upon acceptable safety results through 24 hours for the sentinel subjects per 
Investigator in consultation with the Sponsor and with explicit agreement from the Sponsor. 
Subjects were housed at the CRU for observation for at least 48 hours after dosing. Subjects 
returned for the EOS Visit at 28 days after the dose. Progression to and the dose level for the 
next cohort were dependent upon safety data through Day 3 from the previous cohort. The 
Schedule of Assessments for Part A is provided in Appendix A. Maximum duration of study 
participation (Screening through EOS Visit) for an individual subject was approximately 
56 days. 


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Table 2: 
SAD Dose Cohorts in Healthy Subjects (Part A) 
Cohort 
Dose 
A1 (sentinel group) 
Single dose of AT-007 oral capsule, dose 0.5 mg/kg (n=1) 
placebo (n=1) 
A1 (remainder of 
cohort) 
Single dose of AT-007 oral capsule, dose 0.5 mg/kg (n=5) 
placebo (n=1) 
A2  
Single dose of AT-007 oral capsule, dose 5 mg/kg (n=6) 
placebo (n=2) 
A3 
Single dose of AT-007 oral capsule, dose 10 mg/kg (n=6) 
placebo (n=2) 
A4 
Single dose of AT-007 oral capsule, dose 20 mg/kg (n=6) 
placebo (n=2) 
A5 
Single dose of AT-007 oral capsule, dose 40 mg/kg (n=6) 
placebo (n=2) 
n = number of subjects; SAD = single ascending dose. 
Note: The number of cohorts and total number of subjects may increase if doses above 40 mg/kg are tested in 
additional cohorts (see Section 1.4). This table has been updated to reflect the dose levels actually tested in 
completed Cohorts A1 through A5. At this time, no additional cohorts are planned in Part A. 
3.3.2. 
Part B: Double-blind Multiple Ascending Dose (MAD) in Healthy Subjects  
Four dose levels are planned for the MAD group in Part B (Table 3). Subjects will be enrolled in 
4 sequential cohorts of 6 or 8 subjects each, for a total of 28 subjects. The initial dose level for 
Part B (5 mg/kg) was based on the results from Part A Cohorts A1 through A4. Subjects will 
receive study drug (AT-007 or placebo) QD for 7 consecutive days. Subjects will be housed at 
the CRU for observation from Day -1 (day before the first dose) through at least 48 hours after 
the last dose. Subjects will return for the EOS Visit at 28 days after the last dose. Progression to 
and the dose level for the next cohort will be dependent upon safety data through Day 8 from the 
previous cohort as well as results from Part A. The Schedule of Assessments for Part B is 
provided in Appendix B. Maximum duration of study participation (Screening through EOS 
Visit) for an individual subject will be approximately 63 days. 
Table 3: 
MAD Dose Cohorts in Healthy Subjects (Part B) 
Cohort 
Dose 
B1 
AT-007 oral capsule QD for 7 consecutive days, dose 5 mg/kg (n=6) 
placebo (n=2) 
B2  
AT-007 oral capsule QD for 7 consecutive days, dose 10 mg/kg (n=4) 
placebo (n=2) 
B3 
AT-007 oral capsule QD for 7 consecutive days, dose 20 mg/kg (n=6) 
placebo (n=2) 
B4 
AT-007 oral capsule QD for 7 consecutive days, dose 40 mg/kg (n=4) 
placebo (n=2) 
n = number of subjects; MAD = multiple ascending dose; QD = once daily.  
Note: The number of cohorts and total number of subjects may increase if doses above 40 mg/kg are tested in 
additional cohorts (see Section 1.4). The numbers of subjects in the cohorts are intended to ensure at least 6 subjects 
on AT-007 at each well-tolerated dose level when Cohort C subjects at the same dose level are considered. This 
table has been updated to reflect the dose levels actually tested in completed Cohorts B1, B2, and B3 and the 
planned dose in Cohort B4. 
3.3.3. 
Part C: Open-label Multiple Ascending Dose (MAD) in Healthy Subjects  
The first cohort of Part C (i.e., Cohort C1) was conducted concurrently with Cohort B3 but at 
different locations with the same CRU, and the second cohort of Part C (Cohort C2) was 
conducted after Cohort B3. Cohort C1 used the same dose (10 mg/kg) as Cohort B2; Cohort C2 


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used the same dose (20 mg/kg) as Cohort B3; and Cohort C3 will use the same dose as and run 
concurrently with Cohort B4 (40 mg/kg) (Table 4). Results for prior Part C cohorts will be 
considered before starting the next Part C cohort. Each of the cohorts in Part C will consist of 
only 4 subjects and all subjects will be assigned to open-label AT-007. The subjects will follow 
the same schedule as the subjects in Part B except that subjects in Part C will have a lumbar 
puncture at approximately Tmax after the last dose (Day 7 dose) for the collection of CSF 
(Appendix C). 
Table 4: 
MAD Dose Cohorts in Healthy Subjects with CSF Collection (Part C) 
Cohort 
Dose 
C1 
AT-007 oral capsule QD for 7 consecutive days, dose 10 mg/kg (n=4) 
C2  
AT-007 oral capsule QD for 7 consecutive days, dose 20 mg/kg (n=4) 
C3  
AT-007 oral capsule QD for 7 consecutive days, dose 40 mg/kg (n=4) 
n = number of subjects; MAD = multiple ascending dose; QD = once daily.  
This table has been updated to reflect the dose levels actually tested in completed Cohorts C1 and C2 and the 
planned dose in Cohort C3. 
3.3.4. 
Part D: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) in 
Subjects with Classic Galactosemia (CG)  
Three dose levels are planned for the subjects with CG (Table 5). Subjects will be enrolled in 
3 sequential cohorts of 6 subjects each for a total of up to 18 subjects. The initial dose level for 
Part D was based on the results from Cohorts A1 through A4 and Cohorts B1 and B2. Subjects 
will receive study drug (AT-007 or placebo) on Day 1 and remain at the CRU for at least 
48 hours after the first dose. Subjects will then have a 5-day washout period (Day 1 postdose 
through Day 6 predose). Then, subjects who tolerated the single dose will take the same study 
drug QD for 27 consecutive days (Day 6 through Day 32, inclusive) for the multiple dosing 
portion of Part D. (Note: For each individual subject, the Investigator and the Sponsor will 
decide whether the subject can start the multiple dosing portion of Part D. The Investigator 
must consult the Sponsor. Starting the multiple dosing portion requires explicit agreement 
from the Sponsor.) In the 27-day multiple dosing portion, subjects will take most of their doses 
at home (fasting conditions [Section 5.3] recommended). Subjects will return to the site for brief 
in-clinic stays after the first week of multiple dosing and at the end of multiple dosing as 
indicated in the Schedule of Assessments for Part D (Appendix D). Subjects will return for the 
EOS Visit at 28 days after the last dose. 
Progression to and the dose level for the next cohort will be dependent upon safety data through 
Day 12 and at least single dose PK and galactitol results from the previous cohort as well as 
additional Part B (and possibly Part C) results.  
The Schedule of Assessments for Part D is provided in Appendix D. Maximum duration of study 
participation (Screening through EOS Visit) for an individual subject will be approximately 
100 days. 


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Table 5: 
Dose Cohorts in Subjects with Classic Galactosemia (Part D) 
Cohort 
Dose 
D1 
AT-007 oral capsule on Day 1, dose 5 mg/kg (SAD portion), followed by a 5-day-
washout, and AT-007 oral capsule QD for 27 days (MAD portion), dose 5 mg/kg 
(n=4) 
placebo (n=2) 
D2  
AT-007 oral capsule on Day 1, dose 20 mg/kg (SAD portion), followed by a 5-day-
washout, and AT-007 oral capsule QD for 27 days (MAD portion), dose 20 mg/kg 
(n=4) 
placebo (n=2) 
D3 
AT-007 oral capsule on Day 1, dose TBD mg/kg (SAD portion), followed by a 5-day-
washout, and AT-007 oral capsule QD for 27 days (MAD portion), dose TBD mg/kg 
(n=4) 
placebo (n=2) 
n = number of subjects; MAD = multiple ascending dose; QD = once daily; SAD = single ascending dose; TBD = to 
be determined.  
Note: The number of cohorts and total number of subjects may increase if doses above 40 mg/kg are tested in 
additional cohorts (see Section 1.4). The overall number of subjects per cohort may be increased up to 8 subjects 
to address any potential lost-to-follow-up among subjects treated with either placebo or AT-007. Subjects treated 
with study drug (placebo or AT-007) in a cohort may be randomized to treatment in another cohort (separate 
consent required) within the same Part (assuming no safety or tolerability issues in the prior cohort) as long as 
there is a washout period ≥5 days between the last dose in a cohort and the first dose in the next cohort. This table 
has been updated to reflect the dose levels actually tested in completed Cohorts D1 and D2. The dose level for 
Cohort D3 is TBD as of the writing of protocol version 5.0. 
3.3.5. 
Part E: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) in 
Subjects with GALK-deficient Galactosemia 
The starting dose level for subjects with GALK-deficient Galactosemia will be the most 
clinically appropriate dose as determined by the evaluation of safety, tolerability, and PD 
(reduction in galactitol level) in Part D cohorts completed at the time of starting Part E (Table 6). 
If needed, additional dose levels may be tested in additional cohorts. If applicable, dose levels for 
subsequent cohorts in Part E will be based on safety data through Day 12 and at least single dose 
PK and galactitol results from the previous cohort(s) in Part E and possibly additional cohorts in 
Part D. 
Subjects will receive study drug (AT-007 or placebo) on Day 1 and remain at the CRU for at 
least 48 hours after the first dose. Subjects will then have a 5-day washout period (Day 1 
postdose through Day 6 predose). Then, subjects who tolerated the single dose will take the same 
study drug QD for 27 consecutive days (Day 6 through Day 32, inclusive) for the multiple 
dosing portion of Part E. (Note: For each individual subject, the Investigator and the 
Sponsor will decide whether the subject can start the multiple dosing portion of Part E. 
The Investigator must consult the Sponsor. Starting the multiple dosing portion requires 
explicit agreement from the Sponsor.) In the multiple dosing portion, subjects will take most 
of their doses at home (fasting conditions [Section 5.3] recommended). Subjects will return to 
the site for brief in-clinic stays after the first week of multiple dosing and at the end of multiple 
dosing as indicated in the Schedule of Assessments for Part E (Appendix E). Subjects will return 
for the EOS Visit at 28 days after the last dose. 
The Schedule of Assessments for Part E is provided in Appendix E. Maximum duration of study 
participation (Screening through EOS Visit) for an individual subject will be approximately 
100 days. 


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Table 6: 
Dose Cohort in Subjects with GALK-deficient Galactosemia (Part E) 
Cohort 
Dose 
E1 
AT-007 oral capsule on Day 1, dose TBD mg/kg (SAD portion), followed by a 
5-day-washout, and AT-007 oral capsule QD for 27 days (MAD portion), dose 
TBD mg/kg (n=4) 
placebo (n=2) 
n = number of subjects; MAD = multiple ascending dose; QD = once daily; SAD = single ascending dose; TBD = to 
be determined.  
Note: There may be up to 2 additional cohorts if the decision is made to test more than 1 dose level. Also, the 
number of cohorts and total number of subjects may increase if doses above 40 mg/kg are tested in additional 
cohorts (see Section 1.4). The overall number of subjects per cohort may be increased up to 8 subjects to address 
any potential lost-to-follow-up among subjects treated with either placebo or AT-007. Subjects treated with study 
drug (placebo or AT-007) in a cohort may be randomized to treatment in another cohort (separate consent 
required) within the same Part (assuming no safety or tolerability issues in the prior cohort) as long as there is a 
washout period ≥5 days between the last dose in a cohort and the first dose in the next cohort. 
3.3.6. 
Part D Extension: 90-Day Dosing in Subjects with Classic Galactosemia 
The Part D Extension is open to the following subjects: 
• Subjects who completed Part D may start in the extension at any time after the EOS 
Visit in Part D. 
• Subjects who participated in but discontinued Part D for reasons other than study 
drug related TEAE (and completed an EOS Visit at any time >14 days after the last 
dose) may start in the extension at any time after the EOS Visit in Part D. 
• Subjects who participated in but discontinued Part D for reasons other than study 
drug related TEAE (and who either did not have an EOS Visit or had an EOS Visit 
before 14 days after the last dose) may start in the extension at any time beyond 
14 days after the last dose in Part D. 
• De novo subjects who did not participate in Part D may participate in the 90-day 
Extension after they undergo all the required screening procedures from Day -60 to 
Day -1. 
The dose for the first cohort of the Part D Extension (DE1) will be 20 mg/kg/day based on 
acceptable SAD and MAD safety and PK data from Cohort D2. After SRC review of all SAD 
and MAD data and Sponsor review of PK and galactitol data for Cohorts D1 through D3, a 
second cohort of the Part D Extension (DE2) may be initiated to evaluate a dose >20 mg/kg/day 
if this dose was well tolerated in the SAD and MAD portions of the study in both healthy 
volunteers and subjects with CG.  
A screening visit is required for de novo subjects and subjects whose last visit in Part D was 
>60 days before Day 1 in the Part D Extension. The de novo subjects may also participate in 
optional prescreening. 
Within each cohort of up to 28 subjects, subjects will be randomly assigned in a 3:1 to AT-007 
and placebo. Subjects will receive study drug (AT-007 or placebo) on Day 1 and remain at the 
CRU for at least 24 hours after the first dose. Subjects will receive 1 daily dose of the same study 
drug (AT-007 or placebo) for a total of 90 consecutive days. In the extension, subjects will take 
most of their doses at home (fasting conditions [Section 5.3] recommended). Subjects will have 


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1  in-clinic stay associated with the first dose, a second in-clinic stay associated with the last 
dose, and home health or in-clinic visits at Months 1 and 2 as indicated in the Schedule of 
Assessments for Part D Extension (Appendix F). At any time during Part D Extension, an 
interview with the patient and caregiver (when appropriate) will be performed to assess the 
impact of disease. (detailed processes described in a separate Interview Guide). Subjects will 
return for the EOE Visit at 28 days after the last dose. The EOE Visit will not be required for 
subjects who transition to a separate Open-Label Extenstion Study. For these subjects the EOE 
will be Day 91.  
The Schedule of Assessments for Part D Extension is provided in Appendix F. Maximum 
duration of study participation (Screening through EOE Visit) for an individual subject will be 
approximately 178 days for a de novo subject and approximately 218 days for a subject who was 
screened for Part D, completed Part D, and completed Part D Extension without requiring a 
screening visit for the Part D Extension and without counting any washout period between 
Part D and Part D Extension.  
Table 7: 
90-Day Dose Cohort in Subjects with Classic Galactosemia (Part D 
Extension) 
Cohort 
Dose 
DE1 
AT-007 oral capsule or liquid suspension on Day 1, dose 20 mg/kg (SAD portion), 
followed by AT-007 oral capsule or liquid suspension QD for a total of 90 days, 
dose 20 mg/kg (n=up to 21) 
placebo 
(n=up to 7) 
n = number of subjects; MAD = multiple ascending dose; QD = once daily; SAD = single ascending dose; TBD = to 
be determined.  
Note: There may be up to 1 additional cohort if the decision is made to test more than 1 dose level. Regardless of 
whether there is 1 or 2 cohorts, the maximum number of subjects is 28. However, the number of cohorts and total 
number of subjects may increase if doses above 40 mg/kg are tested in additional cohorts (see Section 1.4). The 
overall number of subjects per cohort may be increased to address any potential lost-to-follow-up among subjects 
treated with either placebo or AT-007. 
3.4. 
Safety Review Committee (SRC) 
An SRC consisting of the Principal Investigator(s) or designee (e.g., a medically qualified 
sub-investigator), the pharmacokineticist, and Sponsor (including external consultants) will meet 
and review the safety data from each cohort in each part of the study. Study progression to the 
next cohort (within each part of the study) will occur only after review of the safety data through 
Day 3 in Part A, Day 8 in Parts B and C, and Day 12 in Parts D and E. 
Safety data to be assessed prior to each dose escalation decision within a part of the study 
include but are not limited to the following: 
• AEs (including dose-limiting toxicities [DLTs], see Section 3.5) 
• Clinical safety laboratory tests (hematology, chemistry, coagulation, urinalysis) 
• Physical examinations 
• Vital signs 
• ECGs 


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In addition, PK data for AT-007 will be considered during all parts of the study. PK data will be 
evaluated by the Sponsor rather than the SRC. Safety and PK data from Cohorts A1 through A4 
in Part A were evaluated by the SRC (safety) and Sponsor (PK) before Part B (MAD) was 
allowed to start. Safety and PK data from Cohorts A1 through A4 in Part A and Cohorts B1 and 
B2 were evaluated before Cohort C1 (MAD with lumbar puncture) or Cohort D1 (subjects with 
CG) were allowed to start. Safety and PK data from these cohorts plus Cohort D2 (and possibly 
Cohorts A5, B4, and D3, depending on timing) will be evaluated before Cohort E1 (subjects with 
GALK-deficient Galactosemia) will be allowed to start. (Notes: Cohort A5 [40 mg/kg] was 
added as part of the amendment resulting in protocol version 4.0 and completed before the 
writing of protocol version 5.0. Addition of Cohort A5 resulted in the addition of Cohort C3 [as 
part of the same protocol amendment that added Cohort A5] and will result in Cohorts B4 and 
D3 [both not yet used as of the writing of protocol version 5.0] being conducted.) Safety and PK 
data from Cohort D2 were evaluated before deciding the dose (20 mg/kg) for Cohort DE1.  
The review of the PK data from Cohorts A1 through A4 and the first 2 cohorts of Part B 
confirmed that once daily (QD) dosing is adequate.  
Safety and PK data from Cohorts A1 through A4 and Cohorts B1, B2, and B3 were evaluated 
before Cohort C2 (MAD with lumbar puncture) was allowed to start.  
Safety and PK data from Cohorts A1 through A5, Cohorts B1 through B3, and Cohorts C1 and 
C2 were evaluated before deciding to start Cohorts B4 and C3 (MAD with lumbar puncture) 
simultaneously at the same dose (40 mg/kg).  
Safety and PK data from Cohorts A1 through A4 and Cohorts B1 and B2 were evaluated before 
Part D (SAD and MAD in subjects with CG) was allowed to start. In addition to safety data 
through Day 12 and at least single dose PK and galactitol results from the previous cohort(s) 
within Part D and safety and PK data from Cohort B3 were evaluated before Cohort D2 was 
allowed to start. Safety and PK data from Cohort B4 will be evaluated before Cohort D3 will be 
allowed to start.  
Safety data through Day 12 and at least single dose PK and galactitol results from all completed 
cohorts within Part D (at least Cohorts D1 and D2 [possibly Cohort D3, depending on timing]) 
will be evaluated before Cohort E1 will be allowed to start. The starting dose for Part E will not 
be higher than the highest acceptable dose in Part D at the time that Part E starts. In case of 
multiple cohorts in Part E, safety data through Day 12 and at least single dose PK and galactitol 
results from previous cohort(s) within Part E will be evaluated before subsequent cohorts in 
Part E will be allowed to start. 
Safety and PK data from Cohort D2 were evaluated before deciding the dose (20 mg/kg) for 
Cohort DE1 (Part D Extension). In case of a second cohort in the Part D Extension, safety data 
through Day 12 and at least single dose PK and galactitol results from all completed cohorts 
within Part D (including Cohort D3) and safety and PK data for Cohorts A5 and B4 will be 
evaluated before deciding upon a dose.  
At each dose escalation decision, the SRC will recommend proceeding or not proceeding to the 
next cohort as well as the dose level for AT-007. The AT-007 dose level may be increased, 
decreased, or repeated from one cohort to the next. 


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Parts A, B, and C will be conducted at a single CRU. The Principal Investigator (or designee) at 
that study center will be part of the SRC during Parts A, B, and C. 
Parts D, E, and D Extension will be conducted at multiple centers. The Principal Investigators (or 
designees) will be part of the SRC during Parts D, E, and D Extension. 
At minimum, the SRC will meet and review data at the following times: 
• Review of safety data through Day 3 for the following cohorts to determine whether 
to proceed with the next cohort and at what dose level:  
o Cohort A1  
o Cohort A2 
o Cohort A3 
o Cohort A4 (At this SRC meeting, a starting dose level for Part B was 
recommended and subsequently confirmed after Sponsor review of all PK data 
from Cohorts A1 through A4.) 
o Cohort A5 (At this SRC meeting, a dose level for both Cohorts B4 and C3 was 
recommended and subsequently confirmed after Sponsor review of all PK data 
from Cohorts A1 through A5.) 
• Review of safety data through Day 8 for the following cohorts to determine whether 
to proceed with the next cohort and at what dose level: 
o Cohort B1 
o Cohort B2 (At this SRC meeting, starting dose level[s] for Part C and Part D were 
recommended and subsequently confirmed after Sponsor review of all PK data 
from Cohorts A1 through A4 and Cohorts B1 and B2.) 
o Cohort B3/C1 (At this SRC meeting, a dose level for Cohorts C2 and D2 was 
recommended and subsequently confirmed after Sponsor review of all PK data 
from Cohorts A1 through A4 and Cohorts B1 through B3 and Cohort C1 as well 
as single dose PK and galactitol data from Cohort D1 and SRC review of safety 
data from Cohort D1.) 
o Cohort C2 
o Cohort B4/C3 (At this SRC meeting, a dose level for Cohort D3 will be 
recommended and require confirmation [or change] after Sponsor review of all 
PK data from all of Parts A and B as well as single dose PK and galactitol data 
from Cohorts D1 and D2. Note: Because Cohorts A5, B4, and C3 are new or 
newly opened, SRC review of safety from Cohorts D1 and D2 was already done 
by the time Cohort A5 was added to the protocol.) 
• Review of safety data through Day 12 (Study Day 12, not the 12th day of multiple 
dosing) for the following cohorts to confirm whether to proceed with the next cohort 
and at what dose level:  
o Cohort D1 


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o Cohort D2 
• Review of safety data through Day 12 (Study Day 12, not the 12th day of multiple 
dosing) for Cohort D3 (At this SRC meeting, a dose level for Cohort E1 may be 
recommended if Cohort E1 has not already started with a dose level not higher than 
that for Cohort D2. A dose level may also be recommended for Cohort DE2. Any 
recommended dose level requires confirmation [or change] after Sponsor review of 
all PK data for Parts A, B, C, and D as well as single dose galactitol data from 
Cohorts D1 through D3.) 
• Review safety data through Day 12 (Study Day 12, not the 12th day of multiple 
dosing) for Cohort E1 to confirm whether to proceed with Cohort E2 and at what 
dose level (if needed) (Any recommended dose level for Cohort E2 requires 
confirmation [or change] after Sponsor review of single dose PK and galactitol data 
from Cohort E1.) 
• Review safety data through Day 12 (Study Day 12, not the 12th day of multiple 
dosing) for Cohort E2 to confirm whether to proceed with Cohort E3 and at what 
dose level (if needed) (Any recommended dose level for Cohort E3 requires 
confirmation [or change] after Sponsor review of single dose PK and galactitol data 
from Cohort E2.) 
• Review of data for the last Part E cohort to finish assessing safety of AT-007 
treatment of subjects with GALK-deficient Galactosemia 
• Review of data for Cohort DE1 (and Cohort DE2 if applicable) to finish assessing 
safety of AT-007 treatment of subjects with CG 
3.5. 
Dose Escalation/De-escalation 
For Parts A, B, and C of the study (healthy subjects), safety and drug exposure will determine 
escalation or de-escalation. If the initial dose tested in Part A had not been well tolerated, the 
Sponsor may have choosen to de-escalate until a well-tolerated dose was identified. A careful 
analysis of available safety, laboratory evaluation, and drug PK data in healthy subjects was done 
to determine the starting dose for Part D in subjects with CG. A careful analysis of available 
safety, laboratory evaluation, and drug PK data in subjects with CG will determine the starting 
dose for Part E in subjects with GALK-deficient Galactosemia. The starting dose in Part E will 
not be higher than the highest acceptable dose used in Part D at the time of starting Part E. The 
starting dose in Part D Extension will be 20 mg/kg based on acceptable SAD and MAD safety 
and PK data from Cohort D2. 
For Part D of the study (subjects with CG), safety, drug exposure, and biomarker analysis of 
galactitol will determine escalation or de-escalation. If the drug exposure in subjects with CG is 
similar to that seen in healthy subjects in Part A, the same or similar approach to dose escalation 
may be utilized. If there is any concern of altered drug exposure or drug clearance based on PK 
analysis after the single dose in the initial cohort of Part D, then alternative dose escalation to 
lower levels may be selected until the relationship between dose and exposure in subjects with 
CG is determined. Dose escalation may be stopped if an effect on galactitol (reduction in 
galactitol) is achieved, but it becomes apparent that higher drug exposure is not increasing 
reduction of galactitol or providing any additional benefit. If any tested dose is not well tolerated 


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while markedly reducing galactitol levels, lower dose levels may be tested until no/minimal 
reduction in galactitol levels is detected. 
In case of multiple cohorts in Parts E, the dose escalation process will be the same as for Part D. 
A second cohort of the Part D Extension (DE2) may be initiated to evaluate a dose higher than 
20 mg/kg/day if this dose was well tolerated in the SAD and MAD portions of the study in both 
healthy volunteers and subjects with CG. 
The SRC will make recommendations to the Sponsor regarding dose escalation or de-escalation 
for each cohort based on the results from the previous cohort as described in Section 3.4. The 
Sponsor will act upon this recommendation and inform the Investigator(s) and the IRB(s)/IEC(s).  
The SRC will pay particular attention to DLTs defined as any AT-007-related AE or clinically 
relevant finding on laboratory tests, ECGs, vital signs, or physical examinations that, in the 
opinion of the Investigator and/or the SRC, precludes administering the dose to any subject 
and/or continuing to administer daily doses to the subject who experienced the event. Specific 
individual subject-level dose stopping criteria for hepatic and renal toxicity are described in 
Appendix G and Appendix H. For DLTs, as well as fatal serious adverse events (SAEs) and 
life-threatening SAEs, breaking the blind will be considered and initiated (as needed) per SRC 
discussion and agreement.  
Dose-escalation will be stopped and de-escalation initiated if: 
• ≥2 subjects on AT-007 (B and C cohorts of the same dose level considered together) 
experience a DLT at any time through 24 hours after the last dose of study treatment 
• Any subject on AT-007 has a fatal SAE or life-threatening SAE requiring urgent 
intervention at any time through 24 hours of the last dose of study treatment 
The maximum tolerated dose (MTD) will be the dose level below the dose level at which one or 
more of the events listed above occurs. 
Dose escalation within each part of the study will continue until the MTD is identified per the 
rules described earlier in this section or the SRC and/or Sponsor decide to stop dose escalation. 
Dose de-escalation, if initiated within any part of the study, will continue until the MTD is 
identified or the SRC and/or Sponsor decide to stop. 
If the events outlined in the above MTD definition do not occur at any dose level in a study part, 
then the MTD will be the highest dose level in that study part.  
If the events outlined in the above MTD definition occur at any given dose level, the Sponsor 
may decide to investigate a dose higher that the previously well-tolerated dose but lower than the 
dose at which one of the events outlined in the above MTD definition occurred. 
3.6. 
Study Termination 
The study will be terminated if the MTD is associated with insufficient drug exposure. 
The study may be discontinued for any clinically significant changes, or pattern of changes (for 
example, clinically significant laboratory abnormalities), that are judged by the Investigator 
and/or Sponsor to be related to the study drug and represent a major tolerability concern. 


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The Principal Investigator reserves the right to terminate the study in the interest of subject 
safety and welfare. The Sponsor reserves the right to discontinue the study due to administrative 
reasons at any time. 


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4. 
SELECTION OF SUBJECTS 
4.1. 
Healthy Subjects in Study Parts A, B, and C 
Subjects must meet all of the inclusion criteria and none of the exclusion criteria to be eligible 
for the study.  
*Criteria that are marked with an asterisk and in bold font also apply to subjects with CG 
and subjects with GALK-deficient Galactosemia. 
4.1.1. 
Inclusion Criteria 
1. Healthy male or non-pregnant, non-lactating female subject between 18 and 65 years of age, 
inclusive. 
2. *Females must be of non-childbearing potential (defined as surgically sterile [i.e., had a 
bilateral tubal ligation, hysterectomy, or bilateral oophorectomy ≥6 months prior to the 
first dose of study drug] or postmenopausal for ≥1 year [confirmatory 
follicle-stimulating hormone or FSH test results required] prior to the first dose of 
study drug) or agree to use an acceptable form of birth control from screening until 
30 days after study completion. 
3. *Males must be unable to procreate (defined as surgically sterile [i.e., had a vasectomy 
≥6 months prior to screening]) or must agree to use an acceptable form of birth control 
from screening through 30 days after study completion. 
4. No significant disease as determined by the Investigator during screening.  
5. *No clinically significant abnormal laboratory value as determined by the Investigator 
during screening. 
6. No significant abnormality on 12-lead ECG as determined by the Investigator during 
screening. 
7. *Subject’s vital signs (measured after 5 minutes rest in a seated position) at screening 
must be within the following ranges: systolic blood pressure (SBP) <140 mmHg; 
diastolic blood pressure (DBP) <90 mmHg; and heart rate between 50 and 100 bpm, 
inclusive. 
8. No regular medical treatment outside of female birth control methods (females of 
childbearing potential only). 
9. *Able to communicate effectively with study personnel. 
10. *Willing and able to be confined to the CRU as required by the protocol. 
11. Willing and able to give written informed consent after being informed of and understanding 
the nature of the study. 
4.1.2. 
Exclusion Criteria 
1. History or presence of clinically significant hematopoietic, renal (estimated glomerular 
filtration rate [eGFR] < 90 mL/min/1.73 m2), hepatic, endocrine, metabolic, pulmonary, 
neurological, psychiatric, cardiovascular, immunological, dermatological, or gastrointestinal 


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diseases; conditions capable of altering the absorption, metabolism, or elimination of drugs; 
or conditions that constitute a risk factor when taking the study drug and/or impact the 
conduct or results of the study. 
2. *Body Mass Index (BMI) >35 kg/m2. 
3. *Underweight or BMI < 17.5 kg/m2. 
4. *Positive test for hepatitis B surface antigen, hepatitis C antibody, or human 
immunodeficiency virus (HIV) at screening or previous treatment for hepatitis B, 
hepatitis C, or HIV infection. 
5. Evidence of significant active neuropsychiatric disease. 
6. Has smoked or used tobacco- or nicotine-containing products ≤6 months prior to the first 
dose of study drug. 
7. *Pregnant, lactating, or not using/not willing to use appropriate means of 
contraception. 
8. *Any prior history of substance abuse (including alcohol) or treatment for such. 
9. Positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, 
cocaine, cannabinoids, opiates) or cotinine. 
10. *History of significant drug allergy or drug hypersensitivity. 
11. *Investigators, site personnel directly affiliated with this study, and their immediate 
families (defined as a spouse, parent, child, or sibling, whether biological or legally 
adopted). 
12. *Any other condition that, in the opinion of the Investigator, precludes the subject from 
following and completing the protocol. 
13. A clinically significant abnormal finding on the physical exam, medical history, ECG, or 
clinical laboratory results at screening. 
14. A significantly abnormal diet (per Investigator judgment) during the 4 weeks preceding the 
first dose of study drug. 
15. *Participation in another clinical trial of a different investigational product 
(randomized subjects only) within 5 half-lives prior to the first dose of study drug.  
16. Use of any over-the-counter (OTC) medication (including nutritional or dietary supplements, 
herbal preparations, or vitamins) ≤7 days prior to the first dose of study drug through the last 
dose of study drug without evaluation and approval by the Investigator. 
17. Use of any prescription medication, except that allowed per protocol (Section 4.6), from 
14 days prior to the first dose of study drug through the last dose of study drug without 
evaluation and approval by the Investigator. 
18. *Treatment with any sensitive substrates of Breast Cancer Resistance Protein (BCRP) 
(e.g., rosuvastatin, sulfasalazine) or potent inhibitors of BCRP (e.g., cyclosporine A) ≤5 
half-lives days prior to the first dose of study drug through the last dose of study drug. 
 


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19. *Treatment with sensitive substrates of Organic Anion Transporter (OAT)1 and OAT3 
(e.g., famotidine, adefovir, furosemide, ganciclovir, cefaclor, ceftizoxime, pen-G) ≤5 
half-lives prior to the first dose of study drug through the last dose of study drug. 
20. *Treatment with sensitive substrates of cytochrome P450 3A4 (CYP3A4) (e.g. 
midazolam, triazolam, buspirone, alfentanil, dronedarone, eletriptan, conivaptan, 
lovastatin, simvastatin), or CYP2B6 (e.g. bupropion), or CYP2C19 (e.g. omeprazole), or 
CYP1A2 (e.g. alosetron, caffeine, duloxetine, melatonin, ramelteon, 
tasimelteon,tizanidine) ≤5 half-lives prior to the first dose of study drug through the last 
dose of study drug 
21. *Consumption of beverages or foods that contain alcohol, high levels of sorbitol, 
grapefruit, poppy seeds, broccoli, Brussels sprouts, pomegranate, star fruit, char-grilled 
meat, or caffeine/xanthine from 48 hours prior to the first dose of study drug through 
the last dose of study drug. Subjects will be instructed not to consume any of the above 
products; however, allowance for an isolated single incidental consumption may be 
evaluated and approved by the Investigator based on the potential for interaction with 
the study drug. 
22. *Treatment with medications potentially associated with transaminase elevations, such 
as mirtazapine ≤5 half-lives prior to the first dose of study drug through the last dose of 
study drug. 
4.2. 
Subjects with Classic Galactosemia (CG) in Study Part D and Part D 
Extension 
Subjects must meet all of the inclusion criteria and none of the exclusion criteria to be eligible 
for the study.  
*Criteria in Section 4.1 that are marked with an asterisk and in bold font also apply to 
subjects with CG (Part D and Part D Extension). 
4.2.1. 
Inclusion Criteria 
1. Male or non-pregnant, non-lactating female subject between the ages of 18 and 65 years, 
inclusive, with a CG diagnosis confirmed by evidence of absent or significantly decreased 
(<1%) GALT activity in red blood cells or historical record of diagnosis of GALT deficiency 
(medical record or gene analysis report or written communication by health care 
professional), and who have no other significant health problems.  
2. Subject may be on concomitant medications and dietary supplements; however, they must be 
on stable doses for at least 1 month prior to screening and throughout the study. 
3. Subject may have long-term complications of Galactosemia, including mild neurological 
deficits such as ataxia, tremor, dysmetria and dystonia, mild cognitive impairment, mild 
language difficulty, and primary ovarian insufficiency, that, in the opinion of the 
Investigator, do not interfere with the subject’s ability to participate in the study. 
4. Galactose-restricted diet that eliminates sources of galactose from dairy products but permits 
minimal dietary intake of galactose from non-dairy products for ≥3 months prior to screening 
and throughout the study. 


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5. Screening 12-lead ECG with normal sinus rhythm without pathological Q wave or significant 
ST/T wave changes. 
6. Willing and able to consent voluntarily to participate in this study by providing written 
informed consent prior to the start of any study-specific procedures, with participation and 
consent of caregiver/LAR as well. 
4.2.2. 
Exclusion Criteria 
1. History or presence of clinically significant hematopoietic, hepatic, endocrine, metabolic 
(other than CG), pulmonary, neurological (other than CG-related), psychiatric, 
immunological, dermatological, or gastrointestinal diseases; conditions capable of altering 
the absorption, metabolism, or elimination of drugs; or conditions that constitute a risk factor 
when taking the study drug and/or impact the conduct or results of the study. 
2. Evidence of diagnosis of clinical variant Galactosemia. 
3. Complications of CG resulting in disability that, in the opinion of the Investigator, may 
prevent the subject from completing all study requirements (e.g., severe neurological deficits, 
severe cognitive impairment, or severe language difficulty). 
4. Impaired renal function or eGFR < 90 mL/min/1.73 m2, or urine protein-to-creatinine ratio 
(UPCR) ≥  200 mg/g, or urine albumin-to- creatinine ratio (UACR) (≥  30 mg/g.Note: eGFR 
and UPCR/UACR are an estimation of renal function, and the ultimate decision of whether a 
patient has normal renal function (and can be included in the study) is at the discretion of the 
Investigator, assuming there are no safety concerns. Also, because eGFR, UPCR and UACR 
can vary day to day based on outside factors, patients can be re-screened for eGFR, UPCR 
and UACR multiple times to understand the renal function of the patient. 
5. History or presence of significant cardiovascular disorders including myocardial infarction, 
stroke, uncontrolled hypertension (sitting blood pressure ≥140/90 mmHg), left ventricular 
(LV) hypertrophy, atrial fibrillation, or valvular heart disease. 
6. Abnormal findings on the screening 12-lead ECG, such as ST/T wave changes of ischemia, 
pathological Q wave changes, or any rhythm other than normal sinus rhythm. 
7. Evidence of significant active hematological disease and/or cumulative blood donation of 
1 unit (500 mL) or more including blood drawn during clinical studies in the last 3 months. 
8. Unwilling to comply with a galactose-restricted diet. 
9. Positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, 
cocaine, cannabinoids, opiates) unless clinically indicated. 
10. Use of any OTC medication (including nutritional or dietary supplements, herbal 
preparations, or vitamins) ≤7 days prior to the first dose of study drug through the last dose 
of study drug without evaluation and approval by the Investigator. Use of medications to 
treat Galactosemia complications will be permitted by approval of the Investigator. 
11. Use of any prescription medication, except that allowed per protocol (Section 4.6), from 
14 days prior to the first dose of study drug through the last dose of study drug without 
evaluation and approval by the Investigator. Use of medications to treat Galactosemia 
complications will be permitted by approval of the Investigator. 


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12. For Part D Extension only, discontinuation due to study drug related TEAE in Part D. 
13. Use of the following following potentially nephrotoxic drugs within 5 half-lives prior to the 
first dose of study drug through the last dose of study drug: amitriptyline, aspirin, doxepin, 
lithium, amphotericin B, foscarnet, ganciclovir, pentamidine, rifampin, antiretrovirals (e.g. 
adefovir, tenofovir), calcineurin inhibitors (e.g. cyclosporine, tacrolimus), angiotensin-
converting enzyme inhibitors, angiotensin receptor blockers, clopidogrel, ticlopidine, 
pamidronate, zoledronate, statins, chemotherapeutics, contrast dye, loop diuretics, thiazides, 
triamterene, allopurinol, gold therapy, haloperidol, quinine, ranitidine. 
4.3. 
Subjects with GALK-deficient Galactosemia in Study Part E 
Subjects must meet all of the inclusion criteria and none of the exclusion criteria to be eligible 
for the study.  
*Criteria in Section 4.1 that are marked with an asterisk and in bold font also apply to 
subjects with GALK-deficient Galactosemia (Part E). 
4.3.1. 
Inclusion Criteria 
Same as for Part D except for Inclusion Criterion 1:  
1. Male and non-pregnant, non-lactating female adult between the ages of 18 and 65 years, 
inclusive, with a GALK-deficient Galactosemia diagnosis documented by historical record of 
either absent or significantly decreased GALK activity in red blod cells (medical record, 
enzyme activity report, genetic mutation report or written communication by health care 
professional) and who have no other significant health problems.  
4.3.2. 
Exclusion Criteria 
Same as for Part D except that “GALK-deficient Galactosemia” replaces “CG” in Exclusion 
Criteria 1 and 3; and the exclusion criterion related to discontinuation from Part D does not 
apply. 
4.4. 
Subject Participation in Multiple Cohorts 
Subjects in Parts D and E may participate in multiple cohorts within the same study Part 
(assuming no safety or tolerability issues in the prior cohort) regardless of whether they are 
treated with AT-007 or placebo in any cohort. However, there must be a washout period ≥5 days 
between the last dose of study drug in a cohort and the first dose of study drug in the next cohort. 
Subject who participates in multiple cohorts must consent to each cohort separately. 
Subjects in Part D may participate in Part D Extension (separate consent required) regardless of 
whether they completed Part D or not as long as Part D discontinuation was not due to a study 
drug related TEAE. The timing from the end of Part D to the start of Part D Extension is 
addressed in Section 3.3.6. A screening visit is required for subjects whose last visit in Part D 
was >60 days before Day 1 in the Part D Extension. However, some screening procedures done 
before Part D do not need to be repeated. 


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4.5. 
Subject Discontinuation Criteria 
For an individual subject, study completion is defined as completing the Treatment Period and 
the EOS or EOE Visit with the exception for subjects that after Part D Extension transition to the 
separate Open-Label Extenstion Study. These subjects will not perform the EOE Visit, hence 
they will complete Part D Extension at the Day 91 Visit..  
Subjects will be free to discontinue the study at any time for any reason. Subjects may be 
discontinued from the study by the Investigator, if necessary, to protect the subjects’ health and 
safety or the integrity of the study data. 
Reasons for discontinuation include, but are not limited to, the following: 
• Adverse event (specify) 
• Pregnancy 
• Withdrawal by subject (specify) 
• Noncompliance or protocol deviation/violation (specify) 
• Lost to follow-up (specify) 
• Other (specify) 
Subjects who discontinue after taking the first dose of study drug will not be replaced. Subjects 
who discontinue before taking study drug will be replaced. 
In the event of a premature study discontinuation, subjects will undergo the procedures for the 
EOS Visit (or EOE Visit if in the Part D Extension) described in Section 6.9. The reason for 
discontinuation must be recorded in the case report form (CRF). 
4.6. 
Medication and Activity Restrictions 
Subjects must not take any OTC medication (including nutritional or dietary supplements, herbal 
preparations, or vitamins) ≤7 days prior to the first dose of study drug until the EOS (or EOE) 
Visit without evaluation and approval by the Investigator. For subjects with CG or GALK-
deficient Galactosemia, use of medications to treat Galactosemia complications will be permitted 
by approval of the Investigator. 
Subjects must not take any prescription medication, except that allowed per protocol in this 
section, from 14 days prior to the first dose of study drug until the EOS (or EOE) Visit without 
evaluation and approval by the Investigator. For subjects with CG or GALK-deficient 
Galactosemia, use of medications to treat Galactosemia complications will be permitted by 
approval of the Investigator. 
In addition, use or consumption of the following are not permitted: 
• Tobacco- or nicotine-containing products within 6 months prior to the first dose of 
study drug (including negative cotinine test at screening) through the EOS Visit 
(subjects in Parts A, B, and C only) 
• Drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, 
opiates) from a negative drug test at screening through the EOS (or EOE) Visit 


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(Exception: Subjects with CG or GALK-deficient Galactosemia may take such drugs 
or drugs that produce positive drug screening results if clinically indicated and on a 
stable dose for ≥1 month prior to screening and throughout the study. Drugs of abuse 
are defined by the local regulations where a patient lives [i.e., a positive result for 
cannabinoids will not be disqualifying if this drug is legal/permitted in the patient’s 
hometown].) 
• Treatment with sensitive substrates of BCRP (e.g., rosuvastatin, sulfasalazine) or 
potent inhibitors of BCRP (e.g., cyclosporine A) within 5 half-lives prior to the first 
dose of study drug through the last dose of study drug 
• Treatment with sensitive substrates of OAT1 and OAT3 (e.g., famotidine, adefovir, 
furosemide, ganciclovir, cefaclor, ceftizoxime, pen-G) within 5 half-lives prior to the 
first dose of study drug through the last dose of study drug 
• Treatment with sensitive substrates of cytochrome P450 3A4 (CYP3A4) (e.g. 
midazolam, triazolam, buspirone, alfentanil, dronedarone, eletriptan, conivaptan, 
lovastatin, simvastatin), or CYP2B6 (e.g. bupropion), or CYP2C19 (e.g. omeprazole), 
or CYP1A2 (e.g. alosetron, caffeine, duloxetine, melatonin, ramelteon, 
tasimelteon,tizanidine) within 5 half-lives prior to the first dose of study drug through 
the last dose of study drug 
• Drugs potentially associated with transaminase elevations, such as mirtazapine within 
5 half-lives prior to the first dose of study drug through the last dose of study drug. 
• Beverages or foods that contain alcohol, high levels of sorbitol, grapefruit, poppy 
seeds, broccoli, Brussels sprouts, pomegranate, star fruit, char-grilled meat, or 
caffeine/xanthine from 48 hours prior to the first dose of study drug through the visit 
before the EOS (or EOE) Visit (allowance for an isolated single incidental consumption 
may be evaluated and approved by the Investigator based on the potential for 
interaction with the study drug) 
• The following following potentially nephrotoxic drugs within 5 half-lives prior to the 
first dose of study drug through the last dose of study drug: amitriptyline, aspirin, 
doxepin, lithium, amphotericin B, foscarnet, ganciclovir, pentamidine, rifampin, 
antiretrovirals (e.g. adefovir, tenofovir), calcineurin inhibitors (e.g. cyclosporine, 
tacrolimus), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, 
clopidogrel, ticlopidine, pamidronate, zoledronate, statins, chemotherapeutics, 
contrast dye, loop diuretics, thiazides, triamterene, allopurinol, gold therapy, 
haloperidol, quinine, ranitidine 
 
If the potential subject is currently taking any of the prohibited medications, a review with the 
investigator with consultation with the sponsor is encouraged. This is due to variability in 
potential drug-drug interactions and interpretation of what medications are sensitive substrates or 
moderate or severe inhibitors or inducers versus AT-007. As such, after investigation an 
exception to an above prohibited medication may be allowed. 
   


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A summary of potential drug-drug interactions (DDI) based on in vitro studies is provided in 
Appendix A. 
Permitted concomitant medications in this study are the following: 
• Female hormonal contraceptives or hormone replacement therapy (Parts A, B, C, D, 
E, and D Extension) 
• Concomitant medications and dietary supplements with stable doses maintained for 
≥1 month prior to screening and through the last dose of study drug (Parts A, B, C, D, 
E, and D Extension) 
• Background medications for the management of subjects with history of seizures 
(Parts D, E, and D Extension) as long as they are not sensitive substrates of BCRP, 
OAT1, OAT3, CYP3A4, CYP2B6, CYP2C19, or CYP1A2 or potent inhibitors of 
BCRP. Patients who switched to an allowed anti-epiletic medication will need to be 
stable on treatment for at least 30 days prior to the first dose of study drug. 
Subjects must not donate blood or plasma from 3 months prior to the first dose of study drug 
through the EOS (or EOE) Visit. It is recommended that blood/plasma donations not be made for 
at least 30 days after the EOS (or EOE) Visit.  
Subject must not engage in strenuous exercise from 48 hours prior to the first dose of study drug 
through the EOS (or EOE) Visit. 
Subjects must stay in the CRU during the time periods designated in the Schedules of 
Assessments (Appendix A, Appendix B, Appendix C, Appendix D, Appendix E, and 
Appendix F). 
4.7. 
Contraception Requirements 
Female subjects must be one of the following: 
• Non-childbearing potential  
OR 
• Childbearing potential and agree to use an acceptable form of birth control from 
screening until 30 days after the EOS (or EOE) Visit 
Women of non-childbearing potential are defined as follows: 
• Surgically sterile (i.e., had a bilateral tubal ligation, hysterectomy, or bilateral 
oophorectomy ≥6 months prior to the first dose of study drug)  
OR 
• Postmenopausal for at least 1 year prior to the first dose of study drug.  
Subjects claiming postmenopausal status will have an FSH test performed at screening to 
confirm postmenopausal status. 
Females of childbearing potential must agree to use an acceptable form of birth control from the 
time point specified in the list below (or screening if no time point specified) until 30 days after 
the EOS (or EOE) Visit. The following are acceptable birth control methods for this study: 


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• Vasectomized partner (at least 6 months prior to dosing); 
• Non-surgical permanent sterilization (e.g., Essure® procedure) at least 3 months prior 
to dosing; 
• Double barrier method (e.g., diaphragm plus condom); 
• Intrauterine device (IUD); 
• Abstinence (and must agree to use a double barrier method if they become sexually 
active during the study); 
• Implanted or intrauterine hormonal contraceptives in use for ≥6 consecutive months 
prior to dosing;  
• Oral, patch, or injected contraceptives, or vaginal hormonal device (i.e., NuvaRing®) 
in use for ≥3 consecutive months prior to dosing. 
Female subjects must agree to provide any requested information about the pregnancy should 
contraception fail and a pregnancy occurs within 90 days after the last dose of study drug. 
A male subject with sexual partners who could become pregnant must meet the following 
criteria: 
• Participant is unable to procreate, defined as surgically sterile (i.e., had a vasectomy 
≥6 months prior to screening) 
OR 
• Participant is able to procreate and agrees to use an acceptable contraceptive method 
from screening until 30 days after the EOS (or EOE) Visit. An acceptable method of 
contraception includes one of the following: 
o Abstinence from heterosexual intercourse 
o Condom with spermicide or condom with intra-vaginally applied spermicide 
Male subjects must agree to provide any requested information about partner pregnancy should 
contraception fail and a pregnancy occurs within 90 days after the subject’s last dose of study 
drug. If a partner pregnancy occurs, consent from the pregnant partner will also be obtained 
before any information about the pregnancy is requested or collected. 


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5. 
STUDY TREATMENTS 
Subjects will be randomly assigned (Section 5.2) to either AT-007 or matching placebo in 
Parts A, B, D, E, and D Extension. The number of subjects to be treated with AT-007 and the 
number of subjects to be treated with placebo in each cohort are described in Section 3.3.  
Subjects will be assigned to open-label AT-007 in Part C. 
5.1. 
Study Drug Supplies 
AT-007 drug substance is manufactured according to current Good Manufacturing Practice 
(GMP) by Worldwide Clinical Trials, Early Phase Services, located in San Antonio, TX. The 
chemical name for AT-007 is 2-(4-oxo-3-((5-(trifluoromethyl)benzo[d]thiazol-2-yl)methyl)-3,4-
dihydrothieno[3,4-d]pyridazin-1-yl)acetic acid. Applied Therapeutics Inc. will supply sufficient 
quantities of the study drug formulation to allow completion of this study. 
AT-007 and matching placebo will be shipped to the appropriate study sites pursuant to site 
standard operating procedures (SOPs). Upon receipt of the study drug products, the supplies will 
be inventoried and stored in an environmentally controlled and secure, limited access area. The 
lot numbers of the drugs along with the expiration dates (where available) will be recorded and 
copies of the Certificate of Analysis (where available) will be maintained on file. Records will be 
maintained of the receipt and dispensation of the drugs supplied. 
Details regarding study drug shiptment, preparation, and dispensation are in a separate pharmacy 
manual. Dosing will be weight based. AT-007 (or matching placebo) will be taken orally, QD, 
under fasted conditions. Doses will be rounded according to the available stock keeping unit 
(SKU) as described in the Pharmacy Manual. 
Retention samples of investigational AT-007 will not be required. At the conclusion of the study, 
any unused study drug will be returned to the Sponsor or destroyed by the study center pursuant 
to written authorization by the Sponsor and applicable regional/local regulations. 
5.2. 
Study Drug Assignment and Blinding 
Up to 116 subjects are planned to be dosed in this study: 
• Part A: 5 cohorts of 8 healthy subjects each 
• Part B: 2 cohorts of 6 healthy subjects each and 2 cohorts of 8 healthy subjects each 
• Part C: 3 cohorts of 4 healthy subjects each 
• Part D: 3 cohorts of 6 subjects with CG each 
• Part E: 1 to 3 cohorts of 6 subjects with GALK-deficient Galactosemia each 
• Part D Extension: 1 to 2 cohorts with a combined total of 28 subjects with CG 
Note: The number of cohorts and total number of subjects may increase if doses above 40 mg/kg 
are tested in additional cohorts (see Section 1.4). In Parts D and E, the overall number of subjects 
per cohort may be increased up to 8 subjects to address any potential lost-to-follow-up among 
subjects treated with either placebo or AT-007. In Parts D and E, subjects treated with study drug 
(placebo or AT-007) in a cohort may be randomized to treatment in another cohort (separate 
consent required) within the same Part (assuming no safety or tolerability issues in the prior 


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cohort) as long as there is a washout period ≥5 days between the last dose in a cohort and the 
first dose in the next cohort. Both de novo and Part D subjects with CG may participate in 
Part D Extension (separate consent required) (see Section 3.3.6 for details regarding when a 
Part D subject can start study drug in the Part D Extension). 
In Parts A, B, D, E, and D Extension, subjects will be randomized to receive either active drug 
(AT-007) or placebo (see Section 3.3 for the number of subjects to be randomized to each 
treatment within each cohort). Each subject will receive an assigned treatment based on the 
randomization schedule prepared by the study statistician.  
Parts A and B will be double-blinded (the Sponsor/CRO, clinical site staff [except for unblinded 
pharmacist for Parts A and B], and the subjects will not know which subjects are treated with 
AT-007 or placebo). 
In Part C, all subjects will be assigned to receive active drug (AT-007). Part C will be open-label. 
In Parts D, E, and D Extension, the clinical site staff (except for the unblinded pharmacist) and 
the subjects will be blinded to study treatment. The Sponsor/CRO will not be blinded to study 
treatment because the relationship between exposure in Parts D, E, and D Extension (subjects 
with galactosemia) vs. exposure in healthy subjects will need to be evaluated on an ogoing basis 
to ensure that AT-007 blood levels remain within the limits achieved in Part B. This process will 
minimize the number of subjects with galactosemia potentially exposed to plasma concentrations 
of AT-007 not previously tested and shown to be safe in healthy subjects. 
5.3. 
Study Drug Administration 
For Parts A, B, and C, subjects will take the study drug (oral capsules of AT-007 or placebo) in 
the CRU under the supervision of study personnel. Study staff will conduct a hand and mouth 
check immediately after dose to ensure that the medication has been appropriately swallowed. 
For Parts D and E, study drug was oral capsules of AT-007 or placebo. For Part D Extension, 
both oral capsules and liquid suspensions will be used. Most study drug doses in Parts D, E, and 
D Extension will be taken on an out-patient basis (i.e., at home). Each subject will be provided 
with a diary card to record the dates/times for all doses taken at home. 
Study drug dose is in mg/kg. For each subject, body weight at screening will be used to 
determine the amount (mg) of study drug in each dose. 
All doses of study drug should be taken under fasting conditions. Subjects should take all doses 
of study drug in the morning (with water) after overnight fasts of at least 10 hours. Subjects may 
end their fast at any time ≥2 hours after taking the study drug. These conditions are mandatory 
for doses associated with PK sampling and recommended for all other doses regardless of 
whether taken at home or in the clinic. 
Subjects may drink water ad libitum. 
5.4. 
Treatment Compliance 
Treatment compliance is assured during Parts A, B, and C and for in-clinic doses during Parts D, 
E, and D Extension because subjects will take the study drug in the CRU under supervision by 
the study center staff.  


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During Parts D, E, and D Extension study drug will be dispensed and collected periodically 
because subjects will be taking most doses at home. Treatment compliance will be determined by 
counting the capsules (or otherwise measuring study drug dispensed to Part D Extension subjects 
taking the liquid suspension) dispensed and collected at each of these visits and by reviewing 
subjects’ study drug diary cards. 
5.5. 
Fasting/Meals/Beverages 
During the stays in the CRU, subjects’ meals and beverages will adhere to the study restrictions 
(Section 4.6). In addition, subjects will be fasted overnight for at least 10 hours before study drug 
administration on the mornings of study drug dosing days and the fast will be broken at ≥2 hours 
after the dose. 
During the out-patient periods of the study, it is recommended that subjects take the study drug 
under the same fasting conditions. Subjects/caregivers will be instructed to have the subject fast 
overnight for at least 10 hours before study drug administration on the mornings of study drug 
dosing days and break the fast at ≥2 hours after the dose. Subjects/caregivers will also be 
instructed to adhere to the study restrictions (Section 4.6) and report any lapses.  
Throughout the study, healthy subjects will maintain their normal/usual diet. 
Throughout the study, subjects with CG or GALK-deficient Galactosemia will maintain their 
normal/usual galactose-restricted diet that eliminates sources of galactose from dairy products 
but permits minimal dietary intake of galactose from non-dairy products. 
Subjects will be encouraged to drink water ad libitum. 


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6. 
STUDY PROCEDURES BY VISIT 
The Schedules of Assessments for Parts A, B, C, D, E, and D Extension of the study are 
provided in Appendix A, Appendix B, Appendix C, Appendix D, Appendix E, and Appendix F, 
respectively. 
The Screening Visit and EOS (or EOE) Visit can be done at any time of day, but the subject 
should arrive in a fasted state after fasting for at least 10 hours. 
For the Check-in Visits for Parts A, B, C, and D Extension, the subject should arrive at the CRU 
around 11 am. For the Check-in Visits for Parts D and E, the subject should arrive at the CRU in 
the morning in a fasted state after fasting for at least 10 hours. The subject should not take study 
drug before arriving at the CRU because study drug will be administered at the visit as needed. 
For the arrival times and conditions of all other visits, please refer to the Schedules of 
Assessments for Parts A, B, C, D, E, and D Extension (Appendix A, Appendix B, Appendix C, 
Appendix D, Appendix E, and Appendix F, respectively). If nothing is stated explicitly regarding 
arrival time, whether the subject should be in a fasted state, and/or whether the subject should 
have taken study drug or not, then assume that the subject can arrive at any time, fasted vs fed 
does not matter, and/or the subject should have taken study drug at home (if during a dosing 
period).  
For each visit, the visit procedures are listed in the approximate order in which they should be 
performed. However, the order of some procedures may be changed for practical reasons (when 
the subject arrives relative to the planned time of dosing and when the subject is able to produce 
a urine sample) as long as the procedures are done within the required timeframe and under the 
required conditions (fasting vs non-fasting and/or before vs after the dose). For example, fasting 
blood and urine samples for clinical safety laboratories are usually written as occurring after the 
dose because of the importance of the timing of the dose; however, the fasting safety laboratory 
samples may be taken at any time before the subject breaks the fast after the dose.  
Acceptable windows for visit procedures are provided in the footnotes in the Schedules of 
Assessments. In case of overlapping time points, meeting the nominal time point for study drug 
dosing and collecting blood samples for PK and/or biomarkers take priority over meeting the 
nominal time point ECGs and vital signs which take priority over meeting the nominal time point 
for physical examinations and collecting samples for clinical safety laboratory tests. 
NOTE: If extenuating circumstances (i.e., COVID-19 pandemic) make clinic visits 
inadvisable/impractical/unwanted for subjects, study visits will be done as home visits by a 
visiting nurse with some equipment/supplies sent to the subjects’ home for the duration of 
their study participation. The details regarding these home health visits are described in a 
separate document entitled “Work Instructions for Conduct of Home Health Protocol 
Visit(s) during COVID-19 Pandemic”. 
6.1. 
Prescreening Period (De novo Part D Extension Subjects Only) 
Prescreening can be done at any time during a home health visit (in-clinic visit also permitted). 
The purpose of prescreening is to identify subjects who may be interested in and qualify for the 
study. A prescreening ICF must be completed before any study-specific prescreening procedure 
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Prescreening is optional. Some subjects may do the prescreening activities as part of screening.  
Prescreening activities may include the following: 
• Collect blood sample for assessment of GALT activity in RBCs and GALT gene 
analysis 
• Collect urine sample (spot collection) for analysis of galactitol 
• Collect fasting blood sample(s) for clinical laboratory testing (hematology, 
coagulation, and chemistry) and serology testing (screening for HIV, hepatitis B, and 
hepatitis C) 
• Measure body weight 
• Measure height 
• Obtainment of medical history only for documented diagnosis of Galactosemia, if 
available 
 
6.2. 
Screening Period (Days -28 through -1 for Parts A, B, and C and 
Days -40 through -1 for Parts D and E, and Days -60 through -1 for 
Part D Extension) 
The screening visit must occur within 28 days before the first dose of study drug for Parts A, B, 
and C; within 40 days before the first dose of study drug for Parts D andE; and within 60 days 
before the first dose of study drug for Part D Extension.  
The Part D Extension screening visit is only applicable to the following subjects: 
• De novo subjects  
• Subjects whose last visit in Part D was >60 days before Day 1 in Part D Extension 
Part D Extension subjects who previously participated in Part D and had a last Part D visit within 
60 days before Day 1 of the extension do not need a screening visit for the extension. 
Subjects will be evaluated at the screening visit to determine their eligibility to enroll in the 
study. The following procedures will be done at screening (home health visit or in-clinic visit): 
• Obtain signed informed consent from the subject and from the subject’s 
caregiver/LAR (if applicable) 
The informed consent documents will be discussed with each potential subject and 
caregiver/LAR (if applicable), and each potential subject (and caregiver/LAR if 
applicable) will sign the informed consent form(s), as appropriate, for the study prior 
to any study-specific procedures being performed. 
• Review inclusion/exclusion criteria 
• Obtain medical history (including current medication)  
• Obtain demographic data (not necessary for Part D subjects being re-screened for 
Part D Extension) 


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• Perform physical examination including height (unless already taken at prescreening) 
and weight 
• Measure vital signs  
• Conduct 12-lead ECG 
• Collect fasting blood sample(s) for clinical laboratory testing (hematology, 
coagulation and biochemistry); serology testing (screening for HIV, hepatitis B, and 
hepatitis C); and, for female subjects of childbearing potential only, serum pregnancy 
test (also FSH test for female subjects claiming postmenopausal status) (Note: The 
clinical laboratory testing and serology testing do not need to be repeated if already 
done at prescreening and prescreening was within 60 days before the first dose of 
study drug in Part D Extension.) 
• Collect fasting urine sample for urinalysis, drugs of abuse screen (also cotinine screen 
for subjects in Parts A, B, and C only), and for the following urinary markers of renal 
function: Urine protein-to-creatinine ratio (UPCR), urine albumin-to- creatinine ratio 
(UACR). 
For Parts D, E, and D Extension only, the following procedures will be done in addition to the 
ones listed above: 
• Collect blood sample for assessment of GALT or GALK activity in red blood cells 
and GALT or GALK gene analysis (GALT for Parts D and D Extension and GALK 
for Part E) (if not already done during prescreening) 
• Collect blood sample for assessment of aldose reductase activity 
• Collect blood sample for analysis of biomarkers of galactose metabolism including 
galactose, galactitol, and galactose-1-p 
• Collect urine sample (spot collection) for analysis of galactitol (if not already done 
during prescreening) 
Note: For Part D Extension subjects who were previously screened for Part D but had the last 
Part D visit >60 days before Day 1 in the extension, GALT and aldose reductase activity 
assessments do not need to repeated.  
Subjects who are taking any disallowed medication(s) (see Section 4.1.2, Section 4.2.2, and 
Section 4.6) but otherwise eligible for the study may washout their disallowed medications 
(washout of at least 5 half-lives of the disallowed medication with the longest half-life). After the 
washout period, they may be rescreened. 
Eligible subjects will be contacted to inform them of their eligibility and schedule the start of 
study drug dosing for those wishing to continue in the study. Subjects (and caregivers if 
applicable for Part D Extension) in Parts A, B, C, and D Extension will be instructed to arrive at 
the CRU at approximately 11 am on the day before the scheduled first dose of study drug. 
Subjects/Caregivers in Parts D and E will be instructed to arrive at the CRU in the morning on 
the day before the scheduled first dose of study drug (i.e., approximately 24 hours before the first 
dose). 


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6.3. 
Clinical Research Unit (CRU) Check-in (All Parts, Day -1) 
Subjects will arrive at the CRU at approximately 11 am (Parts A, B, C, and D Extension) or 
sometime in the morning (Parts D and E [approximately 24 hours before the first dose]) on the 
day before the scheduled first dose of study drug. The following procedures will be done: 
• For Part D Extension subjects who did not have a Part D Extension screening visit 
only, obtain signed informed consent from the subject and from the subject’s 
caregiver/LAR (if applicable) 
• Review of inclusion/exclusion criteria 
• Obtain updates, if any, for medical history  
• Perform physical examination including weight 
• Measure vital signs  
• Conduct 12-lead ECG 
• Collect fasting blood sample(s) for clinical laboratory testing (hematology, 
coagulation and biochemistry); and, for female subjects of childbearing potential 
only, serum pregnancy test (pregnancy test must be negative for the subject to receive 
study drug) 
o Hematology, coagulation and biochemistry laboratory tests do not need to be 
repeated if they were already assessed at the pre-screening or screening visit that 
took place within 60 days prior the first day of docing on Day 1 
• Collect fasting urine sample for urinalysis, drugs of abuse screen (also cotinine screen 
for subjects in Parts A, B, and C only) and for the following urinary markers of renal 
function: UPCR and UACR 
o Urinalysis, UPCR and UACR do not need to be repeated if they were already 
assessed at the pre-screening or screening visit that took place within 60 days 
prior the first day of docing on Day 1 
• Collect AE and concomitant medication data 
• Feed the subject (2 meals [lunch and dinner]) 
• Fast the subject overnight for at least 10 hours 
For Parts D and E only, the following procedures will be done in addition to the ones listed 
above: 
• Collect blood sample for analysis of biomarkers of galactose metabolism including 
galactose, galactitol, and galactose-1-p 
• Collect urine over 24 hours (morning of Day -1 to immediately before the first dose 
[Day 1]) for analysis of galactitol (an aliquot of the total urine collected will be 
analyzed for creatinine) 
• Feed the subject (2 to 3 meals depending on check-in time) 


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Subjects who no longer fulfill all inclusion criteria and/or now fulfill one or more exclusion 
criteria will be discontinued from the study and sent home. These subjects will be replaced. 
Subjects who continue to fulfill all inclusion criteria and none of the exclusion criteria will 
continue in the study. 
6.4. 
Day 1 through Penultimate Visit (Part A, Days 1 through 4) 
Exact time points and allowable windows for assessments and sample collection are provided in 
the Schedule of Assessments (Appendix A). 
Subjects will have 1 in-clinic stay: 
• Subjects will remain at the CRU from Check-in at approximately 11 am of Day -1 
until Discharge on Day 3 (Cohorts A1, A2, and A3) or Day 4 (Cohorts A4 and A5).  
6.4.1. 
Day 1 (Study Drug Dosing Day) 
Subjects will remain in the CRU on Day 1. 
The following procedures will be done before study drug administration on Day 1: 
• Measure predose vital signs  
• Conduct predose 12-lead ECG 
• Collect predose blood sample for PK  
• For Cohorts A4 and A5 only, collect predose urine sample for PK 
• Randomly assign the subject to either AT-007 or placebo (Note: Unblinded CRU 
pharmacist will have the randomization schedule.) 
Then, study drug (AT-007 or placebo) will be administered to the subject, and the following 
procedures will be done on Day 1 after the dose: 
• For Cohorts A4 and A5 only, collect postdose urine for PK  
• Collect postdose blood samples for PK  
• Conduct postdose 12-lead ECG 
• Measure postdose vital signs  
• Feed the subject (3 meals with breakfast provided at ≥2 hours postdose) 
Note: Blood/urine collection for PK will continue into Day 2. 
AE and concomitant medication data will be collected both before and after dose administration 
on Day 1. 
6.4.2. 
Days 2 and 3 
Subjects will remain in the CRU on Day 2. Subjects in Cohorts A4 and A5 only will also remain 
in the CRU on Day 3.  
The following procedures will be done: 


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• Measure vital signs on both days 
• Collect AE and concomitant medication data on both days 
• Collect postdose blood sample(s) for PK on both days 
• For Cohorts A4 and A5 only, collect postdose urine for PK on both days (Note: Urine 
collection for PK will continue into Day 4.) 
• Feed the subject (3 meals on Day 2) 
• Additional Day 3 Procedures  
o Perform physical examination including weight 
o Conduct 12-lead ECG 
o Collect fasting blood sample(s) for clinical laboratory testing (hematology, 
coagulation and biochemistry)  
o Collect fasting urine sample for urinalysis and, for female subjects of childbearing 
potential only, urine pregnancy test 
o Schedule the EOS Visit for Day 28 (±2 days)  
o Discharge subject from the CRU (Cohorts A1, A2, and A3 only) and remind 
subject/caregiver to fast overnight for at least 10 hours on the day before the EOS 
Visit and return to the CRU for the EOS Visit before breaking the fast 
o Feed the subject (3 meals) (Cohorts A4 and A5 only) 
6.4.3. 
Day 4 
Day 4 procedures apply only to Cohorts A4 and A5. 
The following procedures will be done on Day 4: 
• Finish the urine collection for PK 
• Collect AE and concomitant medications data 
• Schedule the EOS Visit for Day 28 (±2 days) 
• Discharge subject from the CRU and remind subject/caregiver to fast overnight for at 
least 10 hours on the day before the EOS Visit and return to the CRU for the EOS 
Visit before breaking the fast 
6.5. 
Day 1 through Penultimate Visit (Part B, Days 1 through 9) 
Exact time points and allowable windows for assessments and sample collection are provided in 
the Schedule of Assessments (Appendix B). 
Subjects will have 1 in-clinic stay:  
• Subjects will remain at the CRU from Check-in at approximately 11 am of Day -1 
until Discharge on Day 9.  


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6.5.1. 
Day 1 (First Study Drug Dosing Day) 
The following procedures will be done before study drug administration on Day 1: 
• Measure predose vital signs  
• Conduct predose 12-lead ECG 
• Collect predose blood sample for PK  
• Randomly assign the subject to either AT-007 or placebo (Note: Unblinded CRU 
pharmacist will have the randomization schedule.) 
Then, study drug (AT-007 or placebo) will be administered to the subject, and the following 
procedures will be done on Day 1 after the dose: 
• Collect postdose blood samples for PK  
• Conduct postdose 12-lead ECG  
• Measure postdose vital signs  
• Feed the subject (3 meals with breakfast provided at ≥2 hours postdose) 
• Fast the subject overnight for at least 10 hours 
Note: Blood collection for PK will continue into Day 2. 
Adverse event and concomitant medication data will be collected both before and after dose 
administration on Day 1. 
6.5.2. 
Day 2 (Study Drug Dosing Day) 
The following procedures will be done on Day 2: 
• Measure vital signs  
• Collect predose blood sample for PK (i.e., 24-hour sample after the Day 1 dose) 
• Administer study drug at approximately the same time of day as on Day 1 
• Feed the subject (3 meals with breakfast provided at ≥2 hours postdose)  
• Fast the subject overnight for at least 10 hours 
• Collect AE and concomitant medication data throughout the day 
6.5.3. 
Days 3, 4, and 5 (Study Drug Dosing Days) 
The subject will take study drug QD at the CRU under fasting conditions (Section 5.3) at 
approximately the same time of day as on Day 1. The subject will be fed 3 meals a day with 
breakfast provided at ≥2 hours postdose. The subject will be fasted for at least 10 hours each 
night before the morning dose. AE and concomitant medication data will be collected. 


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6.5.4. 
Day 6 (Study Drug Dosing Day) 
The following procedures will be done on Day 6: 
• Perform physical examination including weight 
• Measure vital signs  
• Collect fasting blood sample(s) for clinical laboratory testing (hematology, 
coagulation and biochemistry)  
• Collect fasting urine sample for urinalysis and, for female subjects of childbearing 
potential only, urine pregnancy test (pregnancy test must be negative for the subject 
to receive study drug) 
• Administer study drug at approximately the same time of day as on Day 1 
• Feed the subject (3 meals with breakfast provided at ≥2 hours postdose) 
• Fast the subject overnight for at least 10 hours 
• Collect AE and concomitant medication data throughout the day 
6.5.5. 
Day 7 (Last Study Drug Dosing Day) 
The following procedures will be done on Day 7: 
• Measure predose vital signs  
• Conduct predose 12-lead ECG 
• Collect predose blood sample for PK 
• Administer study drug at approximately the same time of day as on Day 1 
• Collect postdose blood samples for PK  
• Conduct postdose 12-lead ECG  
• Measure postdose vital signs  
• Collect AE and concomitant medication data throughout the day 
• Feed the subject (3 meals with breakfast provided at ≥2 hours postdose) 
Note: Blood collection for PK will continue into Days 8 and 9. 
6.5.6. 
Days 8 and 9 
The following procedures will be done on Day 8: 
• Measure vital signs  
• Collect blood samples for PK 
• Collect AE and concomitant medications data  
• Feed the subject (3 meals) 


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The following procedures will be done on Day 9: 
• Perform physical examination including weight 
• Measure vital signs  
• Collect blood sample for PK 
• Collect AE and concomitant medication data  
• Schedule the EOS Visit for Day 35 (±2 days) 
• Discharge subject from the CRU and remind subject/caregiver to fast overnight for at 
least 10 hours on the day before the EOS Visit and return to the CRU for the EOS 
Visit before breaking the fast 
6.6. 
Day 1 through Penultimate Visit (Part C, Days 1 through 9) 
Exact time points and allowable windows for assessments and sample collection are provided in 
the Schedule of Assessments (Appendix C). 
The visit schedule for subjects in Part C is identical to that for subjects in Part B with the 
following exceptions: 
• No randomization. All subjects will receive open-label AT-007. 
• Subjects will have a lumbar puncture on Day 7 (see Appendix C for notes on timing 
of the lumbar puncture relative to the last dose of study drug). 
6.7. 
Day 1 through Penultimate Visit (Parts D and E, Days 1 through 34) 
Exact time points and allowable windows for assessments and sample collection are provided in 
the Schedule of Assessments for Part D (Appendix D) and Part E (Appendix E). 
Subjects will have 3 in-clinic stays.  
• Subjects will remain at the CRU from Check-in on the morning of Day -1 until 
Discharge on Day 3 (Cohorts D1 and D2 and Part E) or Day 4 (Cohort D3).  
• Subjects will remain at the CRU from Check-in on the morning of Day 12 until 
Discharge on Day 13.  
• Subjects will remain at the CRU from Check-in on the morning of Day 32 until 
Discharge on Day 34.  
6.7.1. 
Day 1 (Single Dose) 
Subjects will remain in the CRU on Day 1. 
The following procedures will be done before study drug administration on Day 1: 
• Measure predose vital signs  
• Conduct predose 12-lead ECG 
• Collect predose blood sample for PK 


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• Collect predose blood sample for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p 
• For Cohort D3 only, collect predose urine sample for PK 
• Finish 24-hour predose urine collection for analysis of galactitol 
• Randomly assign the subject to either AT-007 or placebo (Note: Obtain randomized 
treatment assignment by contacting the Interactive Voice/Web Randomization 
System [IVRS/IWRS].) 
Then, study drug (AT-007 or placebo) will be administered to the subject, and the following 
procedures will be done on Day 1 after the dose: 
• Collect 24 hours of postdose urine for analysis of galactitol (an aliquot of the total 
urine collected will be analyzed for creatinine) 
• For Cohort D3 only, collect postdose urine for PK 
• Collect postdose blood samples for PK 
• Collect postdose blood samples for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p 
• Conduct postdose 12-lead ECG  
• Measure postdose vital signs  
• Feed the subject (3 meals with breakfast provided at ≥2 hours postdose) 
Note: Blood/urine collection for PK and/or galactose metabolism will continue into Day 2. 
Adverse event and concomitant medication data will be collected both before and after dose 
administration on Day 1. 
6.7.2. 
Non-dosing Days Between Single and Multiple Dosing (Days 2 through 5) 
Between the single and multiple dosing periods in Part D, there is a 5-day washout period that 
starts immediately after the Day 1 dose and ends immediately before the Day 6 dose (first dose 
of the multiple dosing period). 
6.7.2.1. 
Day 2  
Subjects will remain in the CRU on Day 2. 
The following procedures will be done on Day 2: 
• Finish collecting postdose urine through 24 hours after the dose for analysis of 
galactitol (an aliquot of the total urine collected will be analyzed for creatinine) 
• For Cohort D3 only, collect postdose urine for PK 
• Collect postdose blood samples for PK  
• Collect postdose blood samples for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p  


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• Measure vital signs 
• Collect AE and concomitant medications data  
• Feed the subject (3 meals) 
Note: Blood collection for PK and biomarkers (and urine collection for PK for Cohort D3 only) 
will continue into Day 3. 
6.7.2.2. 
Day 3 
Subjects in Cohort D3 only will remain in the CRU on Day 3. Subjects in Cohorts D1 and D2 
and Part E will be discharged on Day 3. 
The following procedures will be done on Day 3: 
• For Cohort D3 only, collect postdose urine for PK 
• Collect postdose blood sample for PK  
• Collect postdose blood sample for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p 
• Measure vital signs 
• Collect AE and concomitant medications data  
• Discharge subject (Cohorts D1 and D2 and Part E only) from the CRU with a 
reminder to return on the morning of Day 6 after an overnight fast of at least 10 hours  
• Feed the subject (3 meals) (Cohort D3 only) 
Note: For Cohort D3 only, urine collection for PK will continue into Day 4. 
6.7.2.3. 
Day 4 (Cohort D3 Only) 
The following procedures will be done on Day 4: 
• Finish collecting postdose urine for PK  
• Measure vital signs 
• Collect AE and concomitant medications data  
• Discharge subject from the CRU with a reminder to return on the morning of Day 6 
after an overnight fast of at least 10 hours  
6.7.3. 
Day 6 (First Study Drug Dosing Day for Multiple Dosing Period) 
Subjects will arrive in the morning (preferably in time for pre-dose procedures and 8 am dosing). 
The following procedures will be done before study drug administration on Day 6: 
• Perform physical examination including weight 
• Measure predose vital signs  
• Conduct predose 12-lead ECG  


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• Collect fasting blood sample(s) for clinical laboratory testing (hematology, 
coagulation and biochemistry)  
• Collect fasting urine sample for urinalysis and, for female subjects of childbearing 
potential only, urine pregnancy test (pregnancy test must be negative for the subject 
to receive study drug) 
Then, study drug (AT-007 or placebo) will be administered to the subject, and the following 
procedures will be done on Day 6 after the dose: 
• Conduct postdose 12-lead ECG  
• Measure postdose vital signs  
• Feed the subject (breakfast provided at ≥2 hours postdose) 
• Dispense study drug for Days 7 through 11 
• Remind the subject/caregiver that study drug should be taken QD under fasting 
conditions at approximately the same time of day as on Day 6 and to record the 
date/time of each dose on the study drug diary card (Section 5.3) 
• Remind the subject/caregiver to fast overnight for at least 10 hours and return to the 
CRU (before either taking study drug or breaking the fast) on the morning of Day 12 
Adverse event and concomitant medication data will be collected both before and after dose 
administration on Day 6. 
6.7.4. 
Day 12 (Check-in for Second In-clinic Period) 
Subjects will arrive in the morning and check into the clinic. 
The following procedures will be done before study drug administration on Day 12: 
• Collect and record unused study drug and review study drug diary card 
• Perform physical examination including weight 
• Measure predose vital signs  
• Conduct predose 12-lead ECG  
• Collect predose blood sample for PK 
• Collect predose blood sample for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p  
• For female subjects of childbearing potential only, urine pregnancy test (pregnancy 
test must be negative for the subject to receive study drug) 
Then, study drug (AT-007 or placebo) will be administered to the subject, and the following 
procedures will be done on Day 12 after the dose: 
• Start 24-hour postdose urine collection for analysis of galactitol (an aliquot of the 
total urine collected will be analyzed for creatinine) 


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• Collect fasting blood sample(s) for clinical laboratory testing (hematology, 
coagulation and biochemistry)  
• Collect fasting urine sample for urinalysis  
• Collect postdose blood samples for PK 
• Collect postdose blood samples for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p  
• Conduct postdose 12-lead ECG  
• Measure postdose vital signs  
• Feed the subject (3 meals with breakfast provided at ≥2 hours postdose) 
• Fast the subject overnight for at least 10 hours 
Note: Blood collection for PK and galactose metabolism and urine collection for galactitol 
analysis will continue into Day 13. 
Adverse event and concomitant medication data will be collected both before and after dose 
administration on Day 12. 
6.7.5. 
Day 13 (Discharge from Second In-clinic Period) 
The following procedures will be done on Day 13: 
• Finish 24-hour postdose (relative to Day 12 dose) urine collection for analysis of 
galactitol (an aliquot of the total urine collected will be analyzed for creatinine) 
• Collect 24-hour postdose (relative to Day 12 dose) blood sample for PK 
• Collect 24-hour postdose (relative to Day 12 dose) blood sample for analysis of 
biomarkers of galactose metabolism including galactose, galactitol, and galactose-1-p 
• Measure vital signs  
• Administer study drug at approximately 24 hours after the dose on Day 12 
• Collect AE and concomitant medications data  
• Dispense study drug for Days 14 through 19 
• Remind the subject/caregiver that study drug should be taken QD under fasting 
conditions at approximately the same time of day as on Day 6 and to record the 
date/time of each dose on the study drug diary card (Section 5.3) 
• Discharge subject from the CRU and remind the subject/caregiver to fast overnight 
for at least 10 hours and return to the CRU (before either taking study drug or 
breaking the fast) on the morning of Day 20 
6.7.6. 
Day 20 (Out-patient Visit in the Middle of the Multiple Dosing Period) 
Subjects will arrive in the morning. 
The following procedures will be done before study drug administration on Day 20: 


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• Collect and record unused study drug and review study drug diary card 
• Perform physical examination including weight 
• Measure predose vital signs  
• Conduct predose 12-lead ECG 
• For female subjects of childbearing potential only, urine pregnancy test (pregnancy 
test must be negative for the subject to receive study drug) 
Then, study drug (AT-007 or placebo) will be administered to the subject, and the following 
procedures will be done on Day 20 after the dose: 
• Collect fasting blood sample(s) for clinical laboratory testing (hematology, 
coagulation and biochemistry)  
• Collect fasting urine sample for urinalysis  
• Conduct postdose 12-lead ECG  
• Measure postdose vital signs  
• Dispense study drug for Days 21 through 31 
• Remind the subject/caregiver that study drug should be taken QD under fasting 
conditions at approximately the same time of day as on Day 6 and to record the 
date/time of each dose on the study drug diary card (Section 5.3) 
• Remind the subject/caregiver to fast overnight for at least 10 hours and return to the 
CRU (before either taking study drug or breaking the fast) on the morning of Day 32 
Adverse event and concomitant medication data will be collected both before and after dose 
administration on Day 20. 
6.7.7. 
Day 32 (Check-in for Third In-clinic Period and Last Study Drug Dosing Day of 
the Multiple Dosing Period) 
Subjects will arrive in the morning. 
Subjects will remain in the CRU on Day 32. 
The following procedures will be done before study drug administration on Day 32: 
• Collect and record unused study drug and review study drug diary card 
• Perform physical examination including weight 
• Measure predose vital signs  
• Conduct predose 12-lead ECG 
• Collect predose blood sample for PK 
• Collect predose blood sample for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p  


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• For female subjects of childbearing potential only, urine pregnancy test (pregnancy 
test must be negative for the subject to receive study drug) 
Then, study drug (AT-007 or placebo) will be administered to the subject, and the following 
procedures will be done on Day 32 after the dose: 
• Start 24-hour postdose urine collection for analysis of galactitol (an aliquot of the 
total urine collected will be analyzed for creatinine) 
• Collect fasting blood sample(s) for clinical laboratory testing (hematology, 
coagulation and biochemistry)  
• Collect fasting urine sample for urinalysis  
• Collect postdose blood samples for PK 
• Collect postdose blood samples for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p  
• Conduct postdose 12-lead ECG  
• Measure postdose vital signs  
• Feed the subject (3 meals with breakfast provided at ≥2 hours postdose) 
Note: Blood collection for PK and galactose metabolism and urine collection for galactitol 
analysis will continue into Day 33. 
Adverse event and concomitant medication data will be collected both before and after dose 
administration on Day 32. 
6.7.8. 
Day 33 
Subjects will remain in the CRU on Day 33.  
The following procedures will be done: 
• Finish 24-hour postdose urine collection for analysis of galactitol (an aliquot of the 
total urine collected will be analyzed for creatinine) 
• Collect postdose blood samples for PK 
• Collect postdose blood samples for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p 
• Measure vital signs  
• Collect AE and concomitant medications data 
• Feed the subject (3 meals) 
Note: Blood collection for PK and galactose metabolism will continue into Day 34. 
6.7.9. 
Day 34 (Discharge from Third In-clinic Period) 
The following procedures will be done: 
• Collect postdose blood sample for PK 


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• Collect postdose blood sample for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p  
• Perform physical examination including weight 
• Measure vital signs  
• Collect AE and concomitant medications data 
• Schedule the EOS Visit for Day 60 (±2 days) 
• Discharge subject from the CRU and remind subject/caregiver to fast overnight for at 
least 10 hours on the day before the EOS Visit and return to the CRU for the EOS 
Visit before breaking the fast 
6.8. 
Day 1 through Penultimate Visit (Part D Extension, Days 1 through 
91) 
Exact time points and allowable windows for assessments and sample collection are provided in 
the Schedule of Assessments for Part D Extension (Appendix F).  
Subjects will have 2 in-clinic stays.  
• Subjects will remain at the CRU from Check-in on the morning of Day -1 until 
Discharge on Day 2.  
• Subjects will remain at the CRU from Check-in on the morning of Day 90 until 
Discharge on Day 91. 
In lieu of being overnight in the CRU, subjects have the option of staying at a local hotel for Day 
-1 into Day 1 and Day 1 into Day 2. Subjects will abide by all study parameters including 
overnight fasting with all study procedures in the CRU. 
An interview with the patients and their caregivers (wnen appropriate) to assess the impact of 
disease will  be performed at any time during Part D Extension. Detailed processes will be 
described in a separate Interview Guide. 
 
6.8.1. 
Day 1  
Subjects will remain in the CRU on Day 1. 
The following procedures will be done before study drug administration on Day 1: 
• Measure predose vital signs  
• Conduct predose 12-lead ECG 
• Collect predose blood sample for PK 
• Collect predose blood sample for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p 
• Randomly assign the subject to either AT-007 or placebo (Note: Obtain randomized 
treatment assignment by contacting the IVRS/IWRS.) 


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Then, study drug (AT-007 or placebo) will be administered to the subject, and the following 
procedures will be done on Day 1 after the dose: 
• Conduct postdose 12-lead ECG  
• Measure postdose vital signs  
• Feed the subject (3 meals with breakfast provided at ≥2 hours postdose) 
• Fast the subject overnight for at least 10 hours 
Adverse event and concomitant medication data will be collected both before and after dose 
administration on Day 1. 
6.8.2. 
Day 2 
Subjects will be discharged on Day 2. 
The following procedures will be done on Day 2: 
• Measure vital signs  
• Administer study drug at approximately 24 hours after the dose on Day 1 
• Collect AE and concomitant medications data  
• Dispense study drug for Days 3 through 29 
• Remind the subject/caregiver that study drug should be taken QD under fasting 
conditions at approximately the same time of day as on Day 1 and to record the 
date/time of each dose on the study drug diary card (Section 5.3) 
• Discharge subject from the CRU and remind the subject/caregiver to fast overnight 
for at least 10 hours and return to the CRU (before either taking study drug or 
breaking the fast) on the morning of Day 30 
6.8.3. 
Day 30, and Day 60  
These visits may be done as either home health visits or as in-clinic visits. The visits should start 
in the morning. Procedures for these 2 visits are the same. 
The following procedures will be done before study drug administration: 
• Collect and record unused study drug and review study drug diary card 
• Perform physical examination including weight 
• Measure predose vital signs  
• Conduct predose 12-lead ECG 
• Collect predose blood sample for PK 
o This should be done 24 hours (±15 minutes) after the dose administered on the 
previous day (Day 29 and Day 59, respectively). 
• Collect predose blood sample for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p 


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o This should be done 24 hours (±15 minutes) after the dose administered on the 
previous day (Day 29 and Day 59, respectively). 
• For female subjects of childbearing potential only, urine pregnancy test (pregnancy 
test must be negative for the subject to receive study drug) 
Then, study drug (AT-007 or placebo) will be administered to the subject, and the following 
procedures will be done after the dose: 
• Collect fasting blood sample(s) for clinical laboratory testing (hematology, 
coagulation and biochemistry)  
• Collect fasting urine sample for urinalysis, UACR and UPCR  
• Conduct postdose 12-lead ECG  
• Measure postdose vital signs  
• Collect postdose blood samples for PK 
• Collect postdose blood samples for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p 
• Schedule the next visit 
• Dispense study drug for the time between this visit and the next visit 
• Remind the subject/caregiver that study drug should be taken QD under fasting 
conditions at approximately the same time of day as on Day 1 and to record the 
date/time of each dose on the study drug diary card (Section 5.3) 
• Remind the subject/caregiver to fast overnight for at least 10 hours and return to the 
CRU (before either taking study drug or breaking the fast) on the morning of the next 
visit 
Adverse event and concomitant medication data will be collected both before and after dose 
administration. 
6.8.4. 
Day 90 (Check-in for Second In-clinic Period and Last Study Drug Dosing Day) 
Subjects will arrive in the morning and will remain in the CRU on Day 90.  
The following procedures will be done before study drug administration: 
• Collect and record unused study drug and review study drug diary card 
• Perform physical examination including weight 
• Measure predose vital signs  
• Conduct predose 12-lead ECG 
• Collect predose blood sample for PK 
o This should be done 24 hours (±15 minutes) after the dose administered on the 
previous day. 


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• Collect predose blood sample for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p 
o This should be done 24 hours (±15 minutes) after the dose administered on the 
previous day. 
• For female subjects of childbearing potential only, urine pregnancy test (pregnancy 
test must be negative for the subject to receive study drug) 
Then, study drug (AT-007 or placebo) will be administered to the subject, and the following 
procedures will be done after the dose: 
• Collect fasting blood sample(s) for clinical laboratory testing (hematology, 
coagulation and biochemistry)  
• Collect fasting urine sample for urinalysis, UACR and UPCR  
• Conduct postdose 12-lead ECG  
• Measure postdose vital signs  
• Collect postdose blood samples for PK 
• Collect postdose blood samples for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p 
Adverse event and concomitant medication data will be collected both before and after dose 
administration. 
6.8.5. 
Day 91 (Discharge from Second In-clinic Period) 
The following procedures will be done: 
• Collect postdose blood sample for PK (approximately 24 hours [±15 minutes] after 
the last [Day 90] dose) 
• Collect postdose blood sample for analysis of biomarkers of galactose metabolism 
including galactose, galactitol, and galactose-1-p (approximately 24 hours [±15 
minutes] after the last [Day 90] dose) 
• Collect AE and concomitant medications data 
• Schedule the EOE Visit for Day 118 (±2 days) [Only if subject is not directly entering 
the separate Open-Label Extenstion study] 
• Discharge subject from the CRU and remind subject/caregiver to fast overnight for at 
least 10 hours on the day before the EOE Visit and have the EOE Visit before 
breaking the fast 
6.9. 
EOS or EOE Visit (28 Days After the Last Dose) 
All subjects will return to the CRU for an out-patient EOS Visit at 28 ± 2 days (Part A [Day 28]; 
Parts B and C [Day 35]; Parts D and E [Day 60];) after the last dose. For the Part D Extension, 
the EOE Visit (Day 118 ± 2 days) can be done either as a home health visit or as an out-patient 
visit to the site. The EOE Visit will not be performed if subjects transition to the separate Open-


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Label Extenstion Study. The study completion for these subjects will be the completion of the 
Treatment Period at Day 91. The following procedures will be done: 
• Update medical history (including current medications)  
• Perform physical examination including weight 
• Collect fasting blood sample(s) for clinical laboratory testing (hematology, 
coagulation and biochemistry); and, for female subjects of childbearing potential 
only, serum pregnancy test 
• Collect fasting urine sample for urinalysis, UACR and UPCR  
• Measure vital signs  
• Conduct 12-lead ECG 
• Collect AE and concomitant medication data 
 
6.10. 
Unscheduled Visit 
An unscheduled visit may be performed at any time during the study at the subject’s request or 
as deemed necessary by the Investigator/designee. At a minimum, concomitant medication data, 
AEs, and the date and reason for the unscheduled visit will be recorded. Other tests may be 
performed per Investigator/designee judgement. 


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7. 
STUDY ASSESSMENTS 
Schedules of Assessments for Parts A, B, C, D, E, and D Extension are presented in Appendix A, 
Appendix B, Appendix C, Appendix D, Appendix E, and Appendix F, respectively. Procedures 
will be completed as specified in this protocol unless contraindicated due to a reported AE. 
Assessments will be conducted within the time frames specified in the footnotes in the Schedules 
of Assessments.  
7.1. 
Safety Assessments 
7.1.1. 
Adverse Events 
AEs will be monitored throughout the study. AEs will be collected for each subject from the time 
of informed consent through the EOS (or EOE) Visit. Subjects will be queried in a nonleading 
manner, without specific prompting (e.g., “Has there been any change in your health status since 
your last visit?”).  
Safety reporting requirements are provided in Section 8. 
7.1.2. 
Clinical Laboratory Tests 
Blood and urine samples for routine clinical laboratory tests will be collected at the visits as 
indicated in the Schedules of Assessments for Parts A, B, C, D, E, and D Extension 
(Appendix A, Appendix B, Appendix C, Appendix D, Appendix E, and Appendix F, 
respectively). 
A Clinical Laboratory Improvement Amendments (CLIA) certified laboratory will perform the 
following clinical laboratory tests: 
• Hematology: hemoglobin, hematocrit, total and differential leukocyte count, RBC, 
and platelet count 
• Serum Chemistry: albumin, blood urea nitrogen (BUN), creatinine, total bilirubin, 
alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase 
(ALT), sodium (Na+), potassium (K+), chloride (Cl-), lactate dehydrogenase (LDH), 
calcium (Ca), uric acid, glucose, direct bilirubin (DB), and gamma-glutamyl 
transferase (GGT) 
• Coagulation: prothrombin time (PT) and international normalized ratio (INR) 
• Serology: blood tests for hepatitis B surface antigen, hepatitis C antibody, and HIV 
• Urinalysis by an automated or manual urine “dipstick” method: pH, specific gravity, 
protein, glucose, ketones, bilirubin, blood, nitrite, leukocyte esterase, and 
urobilinogen. If protein, occult blood, nitrite, or leukocyte esterase values are out of 
range, a microscopic examination will be performed. 
• Urine Drug Screen: drugs of abuse (amphetamines, benzodiazepines, barbiturates, 
cannabinoids, cocaine, opiates) 
• Urinary markers of renal function: UACR and UPCR 
• Urine cotinine screen (subjects in Parts A, B, and C only) 


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• Pregnancy test (all female subjects of childbearing potential) 
• FSH (for female subjects claiming postmenopausal status) 
For Parts D, E, and D Extension only, the following tests will be done in addition to the ones 
listed above: 
• GALT (Part D and Part D Extension but only done once for subjects participating in 
both Parts) or GALK (Part E) activity in red blood cells 
• GALT (Part D and Part D Extension but only done once for subjects participating in 
both Parts) or GALK (Part E) gene analysis 
• Aldose Reductase activity (only done once for subjects participating in both Parts D 
and D Extension) 
7.1.3. 
Physical Examinations 
Physical examinations will be performed at the visits as indicated in the Schedules of 
Assessments for Parts A, B, C, D, E, and D Extension (Appendix A, Appendix B, Appendix C, 
Appendix D, Appendix E, and Appendix F, respectively). Height will be measured at the 
Screening Visit only. Weight will be measured as part of all physical examinations. Any time 
during the study after the first dose of study drug, abnormal findings considered to be clinically 
significant by the Investigator/designee will be reported as AEs. 
7.1.4. 
Vital Signs 
Vital signs (blood pressure, pulse rate, respiration rate, and temperature) will be measured at the 
visits as indicated in the Schedules of Assessments for Parts A, B, C, D, E, and D Extension 
(Appendix A, Appendix B, Appendix C, Appendix D, Appendix E, and Appendix F, 
respectively). Additional vital signs measurements may be taken as deemed medically necessary 
by the Investigator/designee. For purposes of qualifying any given subject for study 
participation, out of range vital signs may be repeated once. 
All vital signs measurements will be taken with the subject in a seated position and after the 
subject has been resting in that seated position for at least 5 minutes. Any time during the study 
after the first dose of study drug, abnormal vital sign measurements considered to be clinically 
significant by the Investigator/designee will be reported as AEs. 
7.1.5. 
Electrocardiograms (ECGs) 
ECGs will be performed at the visits as indicated in the Schedules of Assessments for Parts A, B, 
C, D, E, and D Extension (Appendix A, Appendix B, Appendix C, Appendix D, Appendix E, 
and Appendix F, respectively). All ECGs will be done with the subject in a supine position and 
after the subject has been resting in that supine position for at least 5 minutes. 
7.1.6. 
Prior and Concomitant Medications 
Prior medications and concomitant medications will be collected throughout the study from the 
signing of informed consent through the EOS (or EOE) Visit. For each medication (prescription 
and OTC medication [including nutritional or dietary supplements, herbal preparations, or 


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vitamins]), start and stop dates, dosage regimen (dose plus route and frequency of 
administration), and indication will be recorded.  
7.1.7. 
Pregnancy 
Pregnancies will not be documented or reported as AEs. However, if at any time the pregnancy 
falls under the scope and definition of a SAE (Section 8.1.2), it will then be reported as such. 
7.1.8. 
Other Safety Measures 
Medical emergency personnel trained in advanced cardiac life support will be on site to monitor 
subjects during the confinement period in the CRU. Emergency medical equipment including, 
but not limited to, intubation equipment and pulse oximetry shall be maintained on site to 
administer appropriate medical care should it be required. 
Appropriate drugs and medical equipment to treat acute [hypotensive, bronchoconstrictive, or 
anaphylactic] reactions must be immediately available at study centers. Study personnel must be 
trained to recognize and treat these reactions. 
The reason for any use of these emergency personnel/equipment or measures to treat acute 
reactions must be reported as an AE (or SAE, if appropriate). 
7.2. 
Pharmacokinetic (PK) Assessments  
Blood and/or urine samples for PK assessments will be collected at the visits as indicated in the 
Schedules of Assessments for Parts A, B, C, D, E, and D Extension (Appendix A, Appendix B, 
Appendix C, Appendix D, Appendix E, and Appendix F, respectively). Instructions for 
collecting and processing blood and urine samples for AT-007 and possible AT-007 metabolite 
analysis will be provided in a separate laboratory manual. Plasma samples will be analyzed for 
AT-007 using a validated method. PK samples will be stored for possible future analysis of 
AT-007 metabolites. 
Also, for subjects in Part C, a Day 7 lumbar puncture will be done to collect CSF for AT-007 
measurement (Appendix C) using a qualified assay. 


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The PK parameters in Table 8 will be determined for the SAD parts of the study (i.e., Part A, the 
single dose period of Parts D and E). 
Table 8: 
PK Parameters of AT-007 After a Single Dose in Healthy Subjects (Part A) 
and Subjects with Classic Galactosemia (SAD Period of Parts D and E) 
PK Parameter 
Definition 
Cmax 
Maximum concentration, determined directly from individual concentration time data 
Tmax 
Time of the maximum concentration 
λz 
The observed terminal rate constant; estimated by linear regression through at least 3 data 
points in the terminal phase of the log concentration-time profile 
T1/2 
The observed terminal half-life, calculated as: 
z
T

)
2
ln(
2
/
1
=
 
AUClast 
Area under the concentration-time curve from time-zero to the time of the last quantifiable 
concentration; calculated using the linear trapezoidal rule 
AUCinf 
Area under the concentration-time curve from time-zero extrapolated to infinity; calculated 
as: 
z
last
last
C
AUC
AUC

+
=
inf
 
AUCExtrap (%) 
The percentage of AUCinf based on extrapolation 
Clast 
The last quantifiable concentration determined directly from individual concentration-time 
data 
Tlast 
Time of the last quantifiable concentration 
CL/F 
Clearance after extravascular administration, calculated as: 
CL/F = Dose/AUCinf 
Vz/F 
Volume of distribution in the terminal phase, calculated as: 
Vz/F = (CL/F)/λz 


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The PK parameters in Table 9 will be determined for the multiple dosing parts of the study 
(i.e., Part B, Part C, MAD period in Parts D and E, and Part D Extension). 
Table 9: 
PK Parameters of AT-007 During Multiple Dosing in Healthy Subjects 
(Parts B and C) and Subjects with Galactosemia (MAD Period of Parts D 
and E and Part D Extension) 
PK Parameter 
Definition 
Cmax 
Maximum concentration, determined directly from individual concentration time data (Day 1 
and Day of Last Dose) 
Tmax 
Time of the maximum concentration (Day 1 and Day of Last Dose) 
λz 
The observed terminal rate constant; estimated by linear regression through at least 3 data 
points in the terminal phase of the log concentration-time profile (Day of Last Dose only) 
T1/2 
The observed terminal half-life, calculated as: 
z
T

)
2
ln(
2
/
1
=
 (Day of Last Dose only)  
AUCtau 
Area under the concentration-time curve during the 24-hour dosing interval; calculated using 
the linear trapezoidal rule (Day 1 and Day of Last Dose) 
Note: If quantifiable data are not observed through 24 h postdose, AUCtau will be estimated 
using extrapolation (from the time of the last reported concentration to 24 h) and AUClast will 
also be reported.   
AUClast 
Area under the concentration-time curve from time-zero to the time of the last quantifiable 
concentration; calculated using the linear trapezoidal rule (Day of Last Dose; Day 1 if 
quantifiable data are not observed through 24 h postdose) 
AUCinf 
Area under the concentration-time curve from time-zero extrapolated to infinity; calculated 
as: 
z
last
last
C
AUC
AUC

+
=
inf
 (Day of Last Dose only)  
AUCExtrap (%) 
The percentage of AUCinf based on extrapolation (Day of Last Dose only) 
Clast 
The last quantifiable concentration determined directly from individual concentration-time 
data (Day 1 and Day of Last Dose) 
Tlast 
Time of the last quantifiable concentration (Day 1 and Day of Last Dose) 
CL/F 
Clearance after extravascular administration, calculated as: 
CL/F = Dose/AUCtau (Day X),  
where Day X = Day of Last Dose and Dose is the actual dose administered (mg/kg x kg). 
(Day of Last Dose only) 
Note: CL/F/kg may also be reported  
Vz/F 
Volume of distribution in the terminal phase, calculated as: 
Vz/F = (CL/F)/λz (Day of Last Dose only) 
Note: Vz/F/kg may also be reported 
Rac 
The accumulation ratio during multiple dose administration, based on Cmax and AUCtau; 
calculated as:  
Rac (AUCtau) = AUCtau (Day X) / AUCtau (Day 1) 
Rac (Cmax) = Cmax (Day X) / AUCtau (Day 1) 
Note: Rac will be tabulated with the pharmacokinetic parameters on Day X. 
Note: Day X = Day of Last Dose 
Note: Day of Last Dose is Day 7 in Parts B and C, Day 32 in the MAD portion of Parts D and E, and Day 90 in 
Part D Extension. 


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7.3. 
Assessments of Biomarkers of Galactose Metabolism 
In Parts D, E, and D Extension, blood samples for the analysis of galactose and galactose 
metabolites including galactitol and galactose-1-phosphate, and urine samples for the analysis of 
galactitol will be collected at the visits as indicated in the Schedules of Assessment (Appendix D, 
Appendix E, and Appendix F, respectively). Instructions for collecting and processing blood and 
urine samples for these biomarkers will be provided in a separate laboratory manual. Blood and 
urine samples will be analyzed for the levels of galactose (in plasma and urine), and galactose 
metabolites including galactitol (in plasma and urine), and galactose-1-phosphate (erythrocytes) 
using qualified or validated assays. 


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8. 
ADVERSE EVENTS 
Subjects will be monitored for AEs from the signing of informed consent through the EOS (or 
EOE) Visit. The Investigator or a medically qualified designee will review each event. The 
Investigator or designee will assess its relationship to the study drug. Each AE will be graded for 
severity, and the date and time of onset and cessation will be recorded along with any treatment 
given for the AE and any action taken with regard to the study drug. Treatment of any AE will be 
evaluated and managed by a physician, either at the study site or at a nearby hospital or 
emergency room, as appropriate. The AE resolution or outcome will be recorded. All non-serious 
AEs will be reported on a regular basis or as specified by the Sponsor. 
8.1. 
Definitions  
8.1.1. 
Adverse Event (AE) 
An AE is defined as any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. 
An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a drug, without judgment to causality. 
An AE can arise from any use of the drug (e.g., off-label, use in combinations with another drug) 
and from any route of administration, formulation, or dose, including an overdose. AEs may 
include the onset of new illness and the exacerbation of pre-existing conditions. New signs and 
symptoms of underlying disease, or signs and symptoms of emerging disease must be recorded 
as AEs. 
The Investigator/designee should attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis should be documented 
as the AE and not the individual signs/symptoms. 
8.1.2. 
Serious Adverse Event (SAE) 
A SAE is an AE that meets one or more of the following criteria:  
• Results in death 
• Is life-threatening (i.e., a subject is at immediate risk of death at the time of the event, 
not an event where occurrence in a more severe form might have caused death) 
• Requires hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability or incapacity 
• Is a congenital anomaly or birth defect 
• Is an important medical event that may jeopardize the subject or may require a 
medical or surgical intervention to prevent one of the outcomes listed above 
Examples of “important medical events” that are SAEs include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias, or convulsions that do 
not result in in-patient hospitalization. 


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The term "severe" is often used to describe the severity of a specific event (as in mild, moderate, 
or severe); the event itself, however, may be of relatively minor medical significance (such as 
severe headache). This is not the same as "serious," which is based on subject/event outcome or 
action criteria usually associated with events that pose a threat to a subject's life or functioning as 
defined by the criteria above.  
During the study, if a subject has a hospitalization or procedure (e.g., elective surgery) that was 
scheduled before the study entry (i.e., before informed consent for an event/condition that 
occurred before the study), then the hospitalization is considered a therapeutic intervention and 
not the result of a SAE. However, if the event/condition worsens during the study, it should be 
reported as an AE (or SAE, if the event/condition results in a serious outcome such as 
prolongation of hospitalization). 
8.1.3. 
Expectedness 
An AE is considered “unexpected” if the AE is not listed in the Investigator Brochure or is not 
listed with the observed specificity or severity. 
8.2. 
AE Reporting 
All AEs must be collected and recorded in the subject’s study records/source documents, in 
accordance with the Investigator’s normal clinical practice, and on the CRF. 
Each AE will be evaluated by the Investigator or designee for duration (onset/cessation), 
severity, causal relationship to the study drug, seriousness, action taken with the study drug, and 
resolution or outcome. Treatment given for an AE should be recorded as a concomitant 
medication with the AE as the indication for the treatment. Definitions for severity and causal 
relationship to the study drug are presented in Section 8.2.1 and Section 8.2.2, respectively. The 
definition for serious is provided in Section 8.1.2. 
8.2.1. 
AE Severity 
The Investigator or designee will assess the severity of each AE according to the following 
definitions: 
• Mild - Transient symptoms that do not influence performance of the subject’s daily 
activities. Other treatment is not indicated. 
• Moderate - Marked symptoms sufficient to make the subject uncomfortable. 
Moderate influence on performance of the subject’s daily activities. Other treatment 
may be necessary. 
• Severe - Symptoms cause considerable discomfort. Substantial influence on subject’s 
daily activities. May be unable to continue the study, and other treatment may be 
necessary. 


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8.2.2. 
AE Relationship to Study Drug 
The Investigator or designee will assess the relationship of each AE to study drug using his/her 
clinical judgment and according to the following definitions: 
• Probably Related: An adverse event that is probably related to the use of the drug 
• Possibly Related: An adverse event that might be due to the use of the drug. An 
alternative explanation (e.g., concomitant drug, concomitant disease) is inconclusive. 
The relationship in time is reasonable; therefore, the casual relationship cannot be 
excluded. 
• Unlikely Related: An adverse event that might not be due to the use of the drug. An 
adverse event for which an alternative explanation (e.g., concomitant drug, 
concomitant disease) is more likely or the relationship in time suggests that a causal 
relationship is unlikely. 
• Not Related: An adverse event that is not related to the use of the drug. 
For the purposes of regulatory reporting, a casuality of probably or possibly related will be 
mapped to related, while a causality of unlikely or not related will be mapped to unrelated. 
8.3. 
SAE Reporting 
The Investigator or designee will notify the appropriate Sponsor contact immediately after the 
SAE detection, observation, or report of occurrence (regardless of the relationship to study drug). 
The Sponsor contact information for SAE reporting is provided below: 
Primary Contact 
Chief Medical Officer: Riccardo Perfetti, MD, PhD  
Phone office: +1 212-220-9227 
Phone mobile: +1 347-702-3018 
Back-up Contact 
Head of Development: Francesca Lawson, MD  
Phone mobile: +1 610-787-2998 
SAE reports to be submitted to Contract Research Organization (CRO) ICON Safety 
Services 
Email: ICON-Safety-CentralReceipt@iconplc.com 
These SAE reports must contain the following information: 
• Study name/number 
• Study drug 
• Investigator details (name, phone, fax, email) 
• Subject number 
• Subject initials 
• Subject demographics 


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• Clinical event: 
o Description 
o Date of onset 
o Treatment (drug, dose, dosage form) 
o Adverse event relationship to study drug 
o Action taken regarding study drug in direct relationship to the AE If the AE was 
fatal or life-threatening 
o If applicable, cause of death (whether or not the death was related to study drug) 
o If applicable, autopsy findings (if available) 
The person responsible for the study shall take care that the study has been carried out in 
accordance with pharmacovigilance regional/local regulations. 
All SAE reporting will adhere to US Code of Federal Regulations (21 CFR Part 312.32) for IND 
drugs and 21 CFR 314.80 for marketed drugs (15-day alerts) or other regional/local regulations 
as applicable. The IRB(s)/IEC(s) will be notified of the alert reports per applicable regulations. 
All AEs, including SAEs, will be followed to resolution when possible. All AEs and treatments 
administered for these AEs will be recorded on the CRF. 


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9. 
STATISTICS 
9.1. 
Sample Size Determination 
No formal sample size calculation is required. The approximate sample size (up to 40 healthy 
subjects in Part A, up to 40 healthy subjects in Parts B and C combined, up to 46 subjects with 
CG in Part D and Part D Extension combined if no subject participates in both, and up to 
18 subjects with GALK-deficient Galactosemia in Part E) is not based on statistical 
considerations. The number of subjects is typical for Phase 1 studies of this type and is adequate 
to meet study objectives. 
Note: The number of cohorts and/or total number of subjects may increase if the PK data reveal 
an insufficient exposure at 40 mg/kg (see Section 1.4). In Parts D and E, the overall number of 
subjects per cohort may be increased up to 8 subjects to address any potential lost-to-follow-up 
among subjects treated with either placebo or AT-007. In Parts D and E, subjects treated with 
study drug (placebo or AT-007) in a cohort may be randomized to treatment in another cohort 
(separate consent required) within the same Part (assuming subject had no safety or tolerability 
issues in the prior cohort) as long as there is a washout period ≥5 days between the last dose in a 
cohort and the first dose in the next cohort. Subject to certain timing considerations (see 
Section 3.3.6), Part D subjects may also participate in Part D Extension (separate consent 
required). 
9.2. 
Statistical Methods 
Detailed statistical methods will be provided in a Statistical Analysis Plan (SAP) that will be 
finalized before database lock. 
NOTE: Part E and Part D Extension results might not be included in the CSR. If the Part E 
and/or Part D Extension results are not included in the CSR, they will be summarized and 
presented in a separate report or CSR addendum. 
9.2.1. 
General Considerations 
Safety measures including the baseline data will be summarized descriptively within each part 
(Parts A, B, C, D, E, and D Extension) of the study by each cohort (dose level of AT-007 and 
placebo), pooled AT-007 group, and pooled placebo group. Within each part of the study, PK 
data will be summarized by AT-007 dose group using descriptive statistics. In case of repeat 
cohorts, data from all cohorts of the same dose level will be combined for analysis. 
For continuous outcomes, descriptive statistics will include the number of subjects, mean, 95% 
confidence interval (CI) for the mean, standard deviation (SD), median, minimum (Min), 
maximum (Max), 25th percentile, and 75th percentile. For categorical outcomes, the number and 
percentage of subjects will be presented. Descriptive statistics will generally be presented by 
AT-group. For summaries of continuous AT-007 PK concentration and parameter data, the 
coefficient of variation will also be presented. 
For analyses of change from baseline, baseline will generally be defined as the predose 
assessment on Day 1 or Day -1, as scheduled. If this value is unavailable, the last nonmissing 
value prior to dosing will be used. Otherwise, missing observations will be treated as missing at 


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random, and no data imputation will be performed. All data from the CRFs, as well as any 
derived variables, will be presented in data listings. 
SAS® version 9.4 or later will be used for all analyses. 
9.2.2. 
Analysis Populations 
Two analysis populations will be defined: 
• Safety population: The safety population will consist of all subjects who are 
randomized and receive at least 1 dose of study drug. All analyses will be performed 
according to treatment received. This population will be used for all analyses of 
safety data. 
• Pharmacokinetic (PK) population: The PK population will consist of all subjects who 
receive at least 1 dose of AT-007 and have sufficient concentration-time data to 
estimate at least one of the planned PK parameters, as determined by the study 
pharmacokineticist. This population will be used for all analyses of PK and biomarker 
data. 
For Parts D and E, these populations may be defined separately for the SAD and MAD periods. 
9.2.3. 
Subject Disposition  
The number and percentage of subjects screened, screen failed, enrolled, randomized, dosed, and 
completing the study will be summarized. The number and percentage of subjects who 
prematurely discontinue the study will also be summarized along with reasons for 
discontinuation. 
9.2.4. 
Drug Exposure and Compliance 
A data listing, by subject, containing study drug dosing and dosing errors, if any, will be 
provided. Treatment compliance will be summarized using descriptive statistics. 
9.2.5. 
Important Protocol Deviations 
Important protocol deviations (IPDs) will be identified and documented based on a review of 
potential IPDs. The potential IPDs will be identified through programmatic checks of study data, 
as well as through review of selected data listings. The potential IPDs to be reviewed include, but 
are not limited to, subjects who: 
• Did not meet inclusion/exclusion criteria 
• Received disallowed concomitant medication 
• Informed consent date obtained after date of first study procedure 
Additional IPDs may be identified from clinical review of Investigator/designee comments or 
other data. Individual IPDs will be presented in a data listing. 


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9.2.6. 
Demographic and Baseline Characteristics 
Demographic and baseline characteristics (including age, sex, race, ethnicity, weight, height, and 
body mass index) will be summarized using descriptive statistics. No formal statistical analyses 
will be performed. 
The medical history of all subjects as well as the neurological history of subjects with CG and 
subjects with GALK-deficient Galactosemia will be coded by system organ class (SOC) and 
preferred term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) 
version 22.0 or higher. The number and percentage of subjects with abnormal findings in each 
SOC and each PT will be summarized. 
9.2.7. 
Safety Analyses 
The evaluation of safety will be based on the occurrence of treatment-emergent adverse events 
(TEAEs); discontinuations from study drug and/or the study because of AEs; clinical laboratory 
test results, physical examination findings, vital sign evaluations, and 12-lead ECGs results. All 
safety endpoints will be summarized descriptively. No statistical inference will be applied to the 
safety endpoints. Descriptive statistics will be calculated for quantitative safety data and 
frequency counts will be compiled for classification of qualitative safety data. 
AEs will be coded by SOC and PT using MedDRA, version 22.0 or higher.  
TEAEs are defined as AEs with onset on or after the date/time of the first dose of study drug. 
Safety analyses will be described in detail in the SAP. 
9.2.8. 
Pharmacokinetic (PK) Analyses 
PK calculations will be performed using appropriate software, e.g., Phoenix™ WinNonlin® 
(Version 6.3 or higher, Pharsight Corporation) and/or SAS® (Version 9.4 or higher, SAS Institute 
Inc.). 
PK parameters will be calculated using noncompartmental methods, using an appropriate model. 
Concentrations below the lower limit of quantitation (BLQ) will be treated as zero from the time 
of the first quantifiable concentration; embedded and terminal BLQ concentrations will be 
treated as “missing.” Actual sample times, if available, will be used in the PK analysis. 
AT-007 concentration-time data and PK parameters will be summarized by study part and cohort 
(dose level) using descriptive statistics (n, mean, SD, median, minimum, maximum, percent 
coefficient of variation [CV%]).   
Dose proportionality, the proportionality of a change in systemic exposure with a change in dose, 
may be assessed using a power model or other appropriate methods. 
Details of the PK analyses, including any additional exploratory analyses, will be described in 
the SAP. 
9.2.9. 
Biomarker Analyses 
For Parts D, E, and D Extension, blood and urine levels of galactose, galactitol, and its other 
metabolites will be summarized using descriptive statistics. Details of these analyses will be 
provided in the SAP. 


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9.2.10. 
Efficacy Analyses 
Not applicable. 


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10. 
GENERAL CONSIDERATIONS 
10.1. 
Ethical and Regulatory Considerations 
10.1.1. 
Study Conduct 
This research will be carried out in accordance with the protocol, the International Council for 
Harmonisation (ICH), Guideline for GCP: Consolidated Guidance (E6), and applicable 
regulatory requirements including clinical research guidelines established by the Basic Principles 
defined in the US 21 CFR Parts 50, 56, and 312; other applicable regional/local regulations, and 
the principles enunciated in the Declaration of Helsinki (revised version Fortaleza 2013). 
10.1.2. 
Institutional Review Boards (IRBs) and Independent Ethics Committees (IECs) 
For all study centers, this protocol will be reviewed by an appropriate IRB/IEC and study 
enrollment will not commence until the IRB/IEC has approved the protocol or a modification 
thereof. The IRB/IEC will be constituted and operated in accordance with the principles and 
requirements in applicable regional/local regulations. 
10.1.3. 
Informed Consent 
Written informed consent will be obtained from each subject (and caregiver/LAR if applicable) 
prior to performing any study-specific procedures. The informed consent document is prepared 
by the Investigator or designee, subject to review and approval by the Sponsor, and forwarded to 
a qualified IRB/IEC for final review and approval. The IRB/IEC-approved consent document 
must contain, at minimum, the 8 basic elements of informed consent. Only the most recently 
IRB/IEC-approved Informed Consent Form (ICF) must be used to consent prospective study 
subjects (and caregivers/LARs if applicable).  
One copy of the signed and dated consent form(s) will be given to the subject (and 
caregiver/LAR if applicable) and the original(s) retained by the Investigator/site. 
10.2. 
Data Collection, Monitoring, Management, and Quality Assurance 
The results from screening and data collected during the study (except clinical laboratory test 
results) will be recorded in the subject’s CRF. 
CRO will be responsible for monitoring the study to ensure compliance with the protocol and 
GCP. Compliance may be verified by one or more of the following methods: on site visits, 
frequent communication with the Investigator, and/or review of CRFs and source documents. On 
site review of CRFs will include a review of forms for completeness and clarity, and consistency 
with source documents available for each subject. The Investigator agrees to permit such 
monitoring as well as audits or reviews by regulatory authorities and the IRB/IEC. 
The study may be subject to audit by the Sponsor/designee and/or Regulatory Agency. If such an 
audit occurs, the Investigator must agree to allow access to required subject records. This is 
dependent on the subject (and caregiver/LAR if applicable) granting consent by signing the ICF. 
By signing this protocol, the Investigator grants permission to personnel from the Sponsor or its 
representatives for on-site monitoring and auditing of all appropriate study documentation, as 


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well as on-site review of the procedures employed in CRF generation, where clinically 
appropriate. 
10.3. 
Study Documentation 
Study records are comprised of source documents, CRFs, and all other administrative 
documents, e.g., IRB/IEC correspondence, clinical study materials and supplies shipment 
manifests, monitoring logs, Sponsor and CRO correspondence, etc. 
A source document is defined as any hand-written or computer-generated document that contains 
medical information or test results that have been collected for or are in support of the protocol 
specifications, e.g., clinical laboratory reports, clinic notes, drug disbursement log, subject 
sign-in sheets, subject-completed questionnaires if applicable, telephone logs, ECGs, etc. All 
draft, preliminary and pre-final iterations of a final report are also considered to be source 
documents, e.g., faxed laboratory reports and hard-copy laboratory reports, faxed initial results 
and hard-copy, final report. 
All documents pertaining to the study, including a copy of the approved protocol, copy of the 
informed consent document and Health Insurance Portability and Accountability Act (HIPAA) 
documents, completed CRFs (where applicable), drug accountability and retention records, and 
other study related documents will be retained in the permanent archives of the study site. These 
will be available for inspection at any time by the Sponsor or the FDA or other applicable 
regulatory agency. Per 21 CFR 312, record retention for this study is required for a period of 
2 years following the date on which this study drug is approved by the FDA for the marketing 
purposes that were the subject of this investigation; or, if no application is to be filed or if the 
application is not approved for such indication, until 2 years following the date on which the 
entire study is completed, terminated, or discontinued, and the FDA is notified. If ex-US, then 
applicable regional/local regulations for records retention will be followed. 
Subject records will be kept private except when ordered by law. The following individuals will 
have access to study subject records: Principal Investigator and designees, study Sponsor, 
monitors, and auditors, the FDA, other applicable regulatory agencies, other government offices, 
and the IRB/IEC. 
10.4. 
Miscellaneous Administrative Information 
The Investigator is referred to the Investigator Brochure or information provided during the 
study initiation visit, information provided by the study monitor, and ICH Guidelines for GCP 
for information regarding the study drug, details, or general considerations to be followed during 
the course of this study. 
Reimbursement, indemnity, and insurance shall be addressed in a separate agreement on terms 
agreed upon by the parties. 
10.5. 
Facilities 
For Parts A, B, and C, which will be conducted at the same CRU, the laboratory at the CRU will 
perform all safety tests.  


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For Parts D, E, and D Extension, which will be conducted in multiple CRUs, local laboratories 
will perform the serum and urine pregnancy tests. A local or central laboratory will perform all 
remaining safety tests. 
Measurements of AT-007 as well as biomarkers of galactose metabolism will be performed by a 
specialized bioanalytical laboratory. 
Instructions for the collection, processing, and/or shipping of various samples are provided in the 
study laboratory manual(s). 


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11. 
REFERENCES 
Augustin R. The protein family of glucose transport facilitators: It’s not only about glucose after 
all. IUBMB Life. 2010;62:NA-NA. doi:10.1002/iub.315. 
Berry GT, Palmieri M, Gross KC, et al. The effect of dietary fruits and vegetables on urinary 
galactitol excretion in galactose1-phosphate uridyltransferase deficiency. J Inherit Metab Dis. 
1993;16:91-100. 
Berry GT. Classic Galactosemia and clinical variant Galactosemia. 04 Feb 2000 [Updated 09 
Mar 2017]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. 
Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: 
https://www.ncbi.nlm.nih.gov/books/NBK1518/. 
Berry GT, Nissim I, Gibson JB, et al. Quantitative assessment of whole-body galactose 
metabolism in galactosemic patients. Eur J Pediatr. 1997;156 Suppl 1:S43-S49. 
Berry GT, Hunter JV, Wang Z, et al. In vivo evidence of brain galactitol accumulation in an 
infant with Galactosemia and encephalopathy. J Pediatr. 2001;138:260–262. 
Daenzer JMI, Jumbo-Lucioni PP, Hopson ML, et al. Acute and long-term outcomes in a 
Drosophila Melanogaster model of Classical Galactosemia occur independently of galaqctose-1-
phosphate accumulation. Dis Model Mech. 2016;9:1375-1382. 
Demirbas D, Coelho AI, Rubio-Gozalbo ME, Berry GT. Hereditary Galactosemia. Y Meta. 
2018. https://doi.org/10.1016/j.metabol.2018.01.025 [unpublished]. 
Fridovich-Keil JL, Gambello MJ, Singh RH, et al. Duarte variant Galactosemia. 04 Dec 2014. In: 
Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): 
University of Washington, Seattle; 1993-2018. Available from: 
https://www.ncbi.nlm.nih.gov/books/NBK258640/. 
Hennermann JB, Schadewaldt P, Vetter B, et al. Features and outcome of galactokinase 
deficiency in children diagnosed by newborn screening. J Inherit Metab Dis. 2011;34:399–407. 
Martineli D, Bernardi B, Napolitano A, et al. Teaching neuro-images: Galactitol peak and fatal 
cerebral edema in Classic Galactosemia. Neurology. 2016;86:e32-e33. 
Meyer WR, Doyle MB, Grifo JA, et al. Aldose reductase inhibition prevents galactose-induced 
ovarian dysfunction in the Sprague- Dawley rat. Am J Obst Gynecol. 1992;167(6):1837-1843. 
Otaduy MCG, Leite CC, Lacerda MTC, et al. Proton MR spectroscopy and imaging of a 
galactosemic patient before and after dietary treatment. AJNR. 2006;27:204–207. 
Palmieri M, Mazur A, Berry GT, et al. Urine and plasma galactitol in patients with galactose-l-
phosphate uridyltransferase deficiency Galactosemia. Metabolism. 1999;48(10):1294-1302. 
Rubio-Gozalbo ME, Haskovic M, Bosch AM, et al. The natural history of Classic Galactosemia: 
Lessons from the GalNet registry. Orphanet J of Rare Dis. 2019;14:86 
https://doi.org/10.1186/s13023-019-1047-z. 
Pyhtila BM, Shaw KA, Neumann SE, Fridovich-Keil JL. Newborn screening for Galactosemia in 
the United States: Looking back, looking around, and looking ahead. JIMD Reports. 2014. 
doi:10.1007/8904_2014_302. 


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Waisbren SE, Potter NL, Gordon CM, et al. The adult galactosemic phenotype. J Inherit Metab 
Dis. 2012;35:279–86. 
Yager CT, Chen J, Reynolds R, Segal S. Galactitol and galactonate in red blood cells of 
galactosemic patients. Mol Gen Metab. 2003;80:283–289. 
 


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APPENDIX A. SCHEDULE OF ASSESSMENTS FOR PART A (SAD IN 
HEALTHY SUBJECTS) 


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Schedule of Assessments for SAD in Healthy Subjects (Part A) 
PROCEDURE 
Screening 
(Days -28 to -
1) 
Day -1a 
(Check-in) 
Day 1 
Day 2 
Day 3a 
(Check-
out) 
Day 4a 
(Check-
out) 
EOS Visitb  
(Day 28±2) 
Check-in 
 
Xa 
 
 
 
 
 
Discharge 
 
 
 
 
Xa 
Xa 
 
Informed consent 
X 
 
 
 
 
 
 
I/E criteria 
X 
X 
 
 
 
 
 
Medical history/updates 
X 
X 
 
 
 
 
X 
Demographic data 
X 
 
 
 
 
 
 
Physical examinationc 
X 
X 
 
 
X 
 
X 
Vital signsd 
X 
X 
X 
X 
X 
 
X 
Electrocardiograme 
X 
X 
X 
 
X 
 
X 
Clinical laboratory testing (biochemistry, 
hematology, coagulation, urinalysis, UACR, 
UPCR)f 
X 
X 
 
 
X 
 
X 
HIV and hepatitis B & C testing 
X 
 
 
 
 
 
 
Urine drug/cotinine screen 
X 
X 
 
 
 
 
 
Pregnancy test (female subjects)g 
X 
X 
 
 
X 
 
X 
Drug administration 
 
 
X 
 
 
 
 
Blood sample collection for PK analysish 
 
 
X 
X 
X 
 
 
Urine collection for PK analysisi 
(Cohorts A4 and A5 only)j 
 
 
X 
X 
X 
X 
 
Adverse Events 
 
Throughout Study 
Prior/Concomitant medications 
X 
Throughout Study 
EOS = end-of-study; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; I/E = inclusion/exclusion; PK = pharmacokinetic; 
SAD = single ascending dose; UACR – urinary albumin to creatinine ratio; UPCR = urinary protein to creatinine ratio 
a: Check-in will occur around 11 am on Day -1. For Cohorts A1, A2, and A3, discharge from the clinic will occur on Day 3 after all Day 3 procedures are done 
and blood samples for PK are collected through 48 hours after the dose. For Cohorts A4 and A5, discharge from the clinic will occur on Day 4 after urine for 
PK is collected through 72 hours after the dose. 
b: The EOS visit will be scheduled for 28 (±2) days after the dose of study drug. 
c: All physical examinations will include weight; however, height will be measured only at screening. 
d: Vital signs will be measured at Screening, Day -1 check-in, predose (within 60 min before the dose) on Day 1, at 4 hours (±10 minutes) after the dose on 
Day 1, once daily on Days 2 and 3, and at the EOS visit. 
e: Electrocardiograms will be performed at Screening, Day -1 check-in, predose (within 60 min before the dose) on Day 1, at 2 hours (±10 minutes) after the 
dose on Day 1, on Day 3, and at the EOS visit. 
f:  Samples for clinical safety laboratory tests will be collected under fasting conditions.  


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g: Serum pregnancy tests at Screening, Day -1, and EOS visits; urine pregnancy tests at other time points. Also, female subjects claiming postmenopausal status 
will have that status verified with an FSH test at Screening. Once a female subject is verified as postmenopausal or otherwise not of childbearing potential, 
the subject is exempt for further pregnancy tests. 
h: Blood samples for PK will be collected predose (within 60 min before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours (±5 minutes for all time 
points) after the dose. 
i: Urine for PK will be collected predose (spot collection within 60 min before the dose) and in 4-hour intervals (0 to 4, >4 to 8, >8 to 12, >12 to 16, >16 to 20, 
and >20 to 24) through the first 24 hours after the dose followed by 12-hour intervals (>24 to 36, >36 to 48, >48 to 60, and >60 to 72) from 24 hours postdose 
to 72 hours postdose. Allowable windows for urine collection container changes will be ±30 minutes through the first 24 hours and ±1 hour thereafter. 
j: Cohort A4 = highest originally planned dose level cohort in Part A. Cohort A5 = highest planned dose level cohort in Part A after the protocol amendment 
resulting in protocol version 4.0. 
 


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APPENDIX B. SCHEDULE OF ASSESSMENTS FOR PART B (MAD IN 
HEALTHY SUBJECTS) 


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Schedule of Assessments for MAD in Healthy Subjects (Part B) 
PROCEDURE 
Screening 
(Days -28 to -
1) 
Day -1a 
(Check-in) 
Day 1 
Day 2 
Days 3, 
4, & 5 
Day 6 
Day 7 
Day 8 
Day 9a 
(Check-
out) 
EOS 
Visitb 
(Day 
35±2) 
Check-in 
 
Xa 
 
 
 
 
 
 
 
 
Discharge 
 
 
 
 
 
 
 
 
Xa 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
I/E criteria 
X 
X 
 
 
 
 
 
 
 
 
Medical history/updates 
X 
X 
 
 
 
 
 
 
 
X 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
Physical examinationc 
X 
X 
 
 
 
X 
 
 
X 
X 
Vital signsd 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
Electrocardiograme 
X 
X 
X 
 
 
 
X 
 
 
X 
Clinical laboratory testing 
(biochemistry, 
hematology, coagulation, 
urinalysis)f 
X 
X 
 
 
 
X 
 
 
 
X 
HIV and hepatitis B & C 
testing 
X 
 
 
 
 
 
 
 
 
 
Urine drug/cotinine screen 
X 
X 
 
 
 
 
 
 
 
 
Pregnancy test (female 
subjects)g 
X 
X 
 
 
 
X 
 
 
 
X 
Drug administrationh 
 
 
X 
X 
X 
X 
X 
 
 
 
Blood sample collection 
for PK analysisi 
 
 
X 
X 
 
 
X 
X 
X 
 
Adverse events 
 
Throughout Study 
Prior/Concomitant 
medications 
X 
Throughout Study 
CSF = cerebrospinal fluid; EOS = end-of-study; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; I/E = inclusion/exclusion; 
MAD = multiple ascending dose; PK = pharmacokinetic; QD = once daily. 
a: Check-in will occur around 11 am on Day -1 and Discharge will occur on Day 9 after the blood sample for PK is collected at 48 hours after the Day 7 dose 
and all Day 9 procedures are done.  
b: The EOS visit will be scheduled for 28 (±2) days after the last dose of study drug. 
c: All physical examinations will include weight; however, height will be measured only at screening. 


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d: Vital signs will be measured at Screening, check-in on Days -1 and 6, predose (within 60 min before the dose) on Days 1 and 7, at 4 hours (±10 minutes) after 
the dose on Days 1 and 7, once daily on Days 2, 8, and 9, and at the EOS visit. 
e: Electrocardiograms will be performed at Screening, Day -1 check-in, predose (within 60 min before the dose) on Days 1 and 7, at 2 hours (±10 minutes) after 
the dose on Days 1 and 7, and at the EOS visit. 
f:  Samples for clinical safety laboratory tests will be collected under fasting conditions. 
g: Serum pregnancy tests at Screening, Day -1, and EOS visits; urine pregnancy tests at other time points. Also, female subjects claiming postmenopausal status 
will have that status verified with an FSH test at Screening. Once a female subject is verified as postmenopausal or otherwise not of childbearing potential, 
the subject is exempt for further pregnancy tests. On Day 6, the urine pregnancy test must be done (and the result negative) before study drug is administered. 
h: All doses of study drug will be administered at the clinic. 
i: On Day 1, blood samples for PK will be collected predose (within 60 minutes before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours (±5 minutes for all 
time points) after the dose. On Day 2, blood samples for PK will be collected predose (i.e., at 24 hours ±5 minutes after the Day 1 dose and before the Day 2 
dose). On Day 7, blood samples for PK will be collected predose (within 60 minutes before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours (±5 minutes 
for all time points) after the dose. Also, blood samples for PK will be collected at 24, 36, and 48 hours (±5 minutes for all time points) after the Day 7 dose; 
these collections will be taken on Day 8 and Day 9. 
 
 
 


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APPENDIX C. SCHEDULE OF ASSESSMENTS FOR PART C (MAD IN 
HEALTHY SUBJECTS) 
 
 


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Schedule of Assessments for MAD in Healthy Subjects (Part C) 
PROCEDURE 
Screening 
(Days -28 to -
1) 
Day -1a 
(Check-in) 
Day 1 
Day 2 
Days 3, 
4, & 5 
Day 6 
Day 7 
Day 8 
Day 9a 
(Check-
out) 
EOS 
Visitb 
(Day 
35±2) 
Check-in 
 
Xa 
 
 
 
 
 
 
 
 
Discharge 
 
 
 
 
 
 
 
 
Xa 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
I/E criteria 
X 
X 
 
 
 
 
 
 
 
 
Medical history/updates 
X 
X 
 
 
 
 
 
 
 
X 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
Physical examinationc 
X 
X 
 
 
 
X 
 
 
X 
X 
Vital signsd 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
Electrocardiograme 
X 
X 
X 
 
 
 
X 
 
 
X 
Clinical laboratory testing 
(biochemistry, 
hematology, coagulation, 
urinalysis)f 
X 
X 
 
 
 
X 
 
 
 
X 
HIV and hepatitis B & C 
testing 
X 
 
 
 
 
 
 
 
 
 
Urine drug/cotinine screen 
X 
X 
 
 
 
 
 
 
 
 
Pregnancy test (female 
subjects)g 
X 
X 
 
 
 
X 
 
 
 
X 
Drug administrationh 
 
 
X 
X 
X 
X 
X 
 
 
 
Blood sample collection 
for PK analysisi 
 
 
X 
X 
 
 
X 
X 
X 
 
Lumbar puncturej  
 
 
 
 
 
 
X 
 
 
 
Adverse events 
 
Throughout Study 
Prior/Concomitant 
medications 
X 
Throughout Study 
CSF = cerebrospinal fluid; EOS = end-of-study; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; I/E = inclusion/exclusion; 
MAD = multiple ascending dose; PK = pharmacokinetic; QD = once daily. 
a: Check-in will occur around 11 am on Day -1 and Discharge will occur on Day 9 after the blood sample for PK is collected at 48 hours after the Day 7 dose 
and all Day 9 procedures are done. 
b: The EOS visit will be scheduled for 28 (±2) days after the last dose of study drug. 


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c: All physical examinations will include weight; however, height will be measured only at screening. 
d: Vital signs will be measured at Screening, check-in on Days -1 and 6, predose (within 60 min before the dose) on Days 1 and 7, at 4 hours (±10 minutes) after 
the dose on Days 1 and 7, once daily on Days 2, 8, and 9, and at the EOS visit. 
e: Electrocardiograms will be performed at Screening, Day -1 check-in, predose (within 60 min before the dose) on Days 1 and 7, at 2 hours (±10 minutes) after 
the dose on Days 1 and 7, and at the EOS visit. 
f:  Samples for clinical safety laboratory tests will be collected under fasting conditions. 
g: Serum pregnancy tests at Screening, Day -1, and EOS visits; urine pregnancy tests at other time points. Also, female subjects claiming postmenopausal status 
will have that status verified with an FSH test at Screening. Once a female subject is verified as postmenopausal or otherwise not of childbearing potential, 
the subject is exempt for further pregnancy tests. On Day 6, the urine pregnancy test must be done (and the result negative) before study drug is administered. 
h: All doses of study drug will be administered at the clinic.  
i: On Day 1, blood samples for PK will be collected predose (within 60 minutes before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours (±5 minutes for all 
time points) after the dose. On Day 2, blood samples for PK will be collected predose (i.e., at 24 hours ±5 minutes after the Day 1 dose and before the Day 2 
dose). On Day 7, blood samples for PK will be collected predose (within 60 minutes before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours (±5 minutes 
for all time points) after the dose. Also, blood samples for PK will be collected at 24, 36, and 48 hours (±5 minutes for all time points) after the Day 7 dose; 
these collections will be taken on Day 8 and Day 9. 
j: A lumbar puncture will be done after the Day 7 dose to collect CSF for analysis of AT-007. For Cohort C1, the timing (hours after the dose) of the lumbar 
puncture was based on PK results from Cohorts B1 and B2. For Cohort C2, the timing of the lumbar puncture was based on PK results from Cohorts B1, B2, 
and B3. For Cohort C2, the timing of the lumbar puncture will be based on PK results from Cohorts B1, B2, B3, and B4. The intent is to perform the lumbar 
puncture at the time of maximum observed concentration (Tmax) after the Day 7 dose. 
Note: The Schedule for Part C will differ from that for Part B only by the lack of randomization on Day 1 and the addition of a Day 7 lumbar puncture. 
 
 
 


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APPENDIX D. SCHEDULE OF ASSESSMENTS FOR PART D (SAD AND 
MAD IN SUBJECTS WITH CLASSIC GALACTOSEMIA) 


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Schedule of Assessments for SAD and MAD in Subjects with Classic Galactosemia (Part D) q 
PROCEDURE 
Screening 
(Days -40 to -1a) 
Day 
1 
Day 
2 
Day 
3b 
Day 
4b 
Day 
5 
Day 
6a 
Day 
12a 
Day 
13b 
Day 
20a 
Day 
32a 
Day 
33 
Day 
34b 
EOS 
Visit 
Day 60 
(±2) 
Check-in 
Xa 
(Day -1) 
 
 
 
 
 
 
Xa 
 
 
Xa 
 
 
 
Discharge 
 
 
 
Xb 
Xb 
 
 
 
Xb 
 
 
 
Xb 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
I/E criteria 
Xr 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history/updates 
Xr 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationd 
Xr 
 
 
 
 
 
X 
X 
 
X 
X 
 
X 
X 
Vital signse 
Xr 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Electrocardiogramf 
Xr 
X 
 
 
 
 
X 
X 
 
X 
X 
 
 
X 
Clinical laboratory testingg 
Xr 
 
 
 
 
 
X 
X 
 
X 
X 
 
 
X 
GALT activity in red blood 
cells and GALT gene analysis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aldose Reductase activity 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV and hepatitis B & C 
testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine drug screen 
Xr 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test (female 
subjects)h 
Xr 
 
 
 
 
 
X 
X 
 
X 
X 
 
 
X 
Drug administrationj 
 
X 
 
 
 
 
QD for 27 days 
 
 
 
5-day washoutk 
 
X 
 
 
 
 
 
 
 
 
Blood sample collection for 
PK analysisl 
 
X 
X 
X 
 
 
 
X 
X 
 
X 
X 
X 
 
Urine collection for PK 
analysism  
(Cohort D3 only)n 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Blood sample collectiono for 
galactose, galactitol, 
galactose-1-p and other 
galactose metabolites 
Xr 
X 
X 
X 
 
 
 
X 
X 
 
X 
X 
X 
 


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PROCEDURE 
Screening 
(Days -40 to -1a) 
Day 
1 
Day 
2 
Day 
3b 
Day 
4b 
Day 
5 
Day 
6a 
Day 
12a 
Day 
13b 
Day 
20a 
Day 
32a 
Day 
33 
Day 
34b 
EOS 
Visit 
Day 60 
(±2) 
Urine sample collectionp for 
galactitol 
Xr 
X 
X 
 
 
 
 
X 
X 
 
X 
X 
 
 
Adverse events 
 
Throughout Study 
Prior/Concomitant 
medications 
Xr 
Throughout Study 
CRU = clinical research unit; EOS = end-of-study; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; I/E = inclusion/exclusion; 
MAD = multiple ascending dose; PK = pharmacokinetic; QD = once daily; SAD = single ascending dose. 
a: Subjects will arrive at the CRU in the morning on Day -1 (approximately 24 hours before the planned first dose). For the Days 12, 20, and 32 check-ins/visits, 
the subject should arrive after an overnight fast of at least 10 hours (and before breaking the fast) and before taking study drug. On Days 6 and 60, the subject 
should not have any study drug in his/her possession and should arrive (in a fasted condition) in the morning (before the planned time of study drug dosing to 
be given in the clinic on Day 6 [no study drug dosing on Day 60]). 
b: Discharge from the 1st, 2nd, and 3rd (last) in-clinic periods of the required portions of Part D will occur on Days 3 (Cohorts D1 and D2) or 4 (Cohort D3), 13, 
and 34, respectively, after all procedures for that day are done and the last blood sample or urine collection for that in-clinic period is collected.  
c: The EOS visit will be scheduled for 28 (±2) days after the last dose of study drug in the MAD portion.  
d: All physical examinations will include weight; however, height will be measured only at screening.  
e: Vital signs will be measured at Screening, every check-in, every check-out, predose (within 60 min before the dose) and 4 hours (±10 minutes) after the dose 
on Days 1, 6, 12, 20, and 32; once daily on all other in-clinic days; and at the EOS visit. 
f: Electrocardiograms will be performed at Screening, Day -1 check-in, predose (within 60 min before the dose) and 2 hours (±10 minutes) after the dose on 
Days 1, 6, 12, 20, and 32 and at the EOS visit. 
g:  Samples for clinical safety laboratory tests (hematology, chemistry, coagulation, and urinalysis) will be collected under fasting conditions. 
h: Serum pregnancy tests at Screening, Day -1, and EOS visits; urine pregnancy tests at other time points. Also, female subjects claiming postmenopausal status 
will have that status verified with an FSH test at Screening. Once a female subject is verified as postmenopausal or otherwise not of childbearing potential, 
the subject is exempt for further pregnancy tests. On Days 6, 12, 20, and 32, the urine pregnancy test must be done (and the result negative) before study drug 
is administered. 
j: On Days 1, 6, 12, 13, 20, and 32, study drug will be administered at the clinic. All other doses of study drug will be taken at home QD with water in the 
morning (preferably after an overnight fast of ≥10 hours with the fast broken ≥2 hours after the dose). Study drug administration should be at approximately 
the same time of day (preferably 8 am) throughout the multiple dosing period. See Section 6.7 for when study drug will be dispensed and/or collected. 
k: The 5-day washout between single and multiple dosing will start immediately after the Day 1 dose and end immediately before the Day 6 dose. There is no 
visit on Day 5; it is in the Schedule of Assessments only for depiction of the 5-day washout. 
l: For the Day 1 dose, blood samples for PK will be collected predose (within 60 minutes before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours 
(±5 minutes for all time points) after the dose. On Days 12 and 32, blood samples for PK will be collected predose (within 60 minutes before the dose) and at 
0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours (±5 minutes for all time points) after the dose. On Day 13, a blood sample for PK will be collected predose (i.e., at 24 hours 
±5 minutes after the Day 12 dose). On Day 33, blood samples for PK will be collected at 24 and 36 hours (±5 minutes for both time points) after the Day 32 
dose. On Day 34, a blood sample for PK will be collected at 48 hours (±5 minutes) after the Day 32 dose.  


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m: For Cohort D3 only, urine for PK will be collected predose (spot collection within 60 minutes before the Day 1 dose) and in 4-hour intervals (0 to 4, >4 to 8, 
>8 to 12, >12 to 16, >16 to 20, and >20 to 24) through the first 24 hours after the Day 1 dose followed by 12-hour intervals (>24 to 36, >36 to 48, >48 to 60, 
and >60 to 72) from 24 to 72 hours after the Day 1 dose. Allowable windows for urine collection container changes will be ±30 minutes through the first 
24 hours and ±1 hour thereafter. 
n: Cohort D3 = highest planned dose level cohort in Part D. 
o: With the exception of the blood samples for biomarkers taken at Screening and Day -1, the time points and allowable windows for the blood samples for 
biomarkers will match those for the blood samples for PK. 
p: Urine for galactitol measurement will be collected over the 24 hours immediately before and the 24 hours immediately after the dose on Day 1. Urine for 
galactitol measurement will be collected over the 24 hours immediately after the dose on Days 12 and 32 during the MAD period. For each 24-hour collection 
of urine for galactitol measurement, an aliquot of the total urine collected will be analyzed for creatinine. Also, a spot collection for urine galactitol 
measurement will be taken at screening. 
q: Visit window +/- 1 day of scheduled visit for all visits except the EOS visit which has a window of +/- 2 days. 
r: These assessments must be performed on Day -1 even if they were already performed earlier during the screening period.  
 
 


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APPENDIX E. SCHEDULE OF ASSESSMENTS FOR PART E (SAD AND 
MAD IN SUBJECTS WITH GALK-DEFICIENT 
GALACTOSEMIA) 


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Schedule of Assessments for SAD and MAD in Subjects with GALK-deficient Galactosemia (PART E) o 
PROCEDURE 
Screening 
(Days -40 to -1a) 
Day 
1 
Day 
2 
Day 
3b 
Day 
5 
Day 
6a 
Day 
12a 
Day 
13b 
Day 
20a 
Day 
32a 
Day 
33 
Day 
34b 
EOS 
Visitc 
Day 60 
(±2) 
Check-in 
Xa 
(Day -1) 
 
 
 
 
 
Xa 
 
 
Xa 
 
 
 
Discharge 
 
 
 
Xb 
 
 
 
Xb 
 
 
 
Xb 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
I/E criteria 
Xp 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history/updates 
Xp 
 
 
 
 
 
 
 
 
 
 
 
X 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationd 
Xp 
 
 
 
 
X 
X 
 
X 
X 
 
X 
X 
Vital signse 
Xp 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Electrocardiogramf 
Xp 
X 
 
 
 
X 
X 
 
X 
X 
 
 
X 
Clinical laboratory 
testingg 
Xp 
 
 
 
 
X 
X 
 
X 
X 
 
 
X 
GALK activity in red 
blood cells and GALK 
gene analysis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Aldose Reductase activity 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HIV and hepatitis B & C 
testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Urine drug screen 
Xp 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test (female 
subjects)h 
Xp 
 
 
 
 
X 
X 
 
X 
X 
 
 
X 
Drug administrationj 
 
X 
 
 
 
QD for 27 days 
 
 
 
5-day washoutk 
 
X 
 
 
 
 
 
 
 
 
Blood sample collection 
for PK analysisl 
 
X 
X 
X 
 
 
X 
X 
 
X 
X 
X 
 
Blood sample collectionm 
for galactose, galactitol, 
galactose-1-p and other 
galactose metabolites 
Xp 
X 
X 
X 
 
 
X 
X 
 
X 
X 
X 
 


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PROCEDURE 
Screening 
(Days -40 to -1a) 
Day 
1 
Day 
2 
Day 
3b 
Day 
5 
Day 
6a 
Day 
12a 
Day 
13b 
Day 
20a 
Day 
32a 
Day 
33 
Day 
34b 
EOS 
Visitc 
Day 60 
(±2) 
Urine sample collectionn 
for galactitol 
Xp 
X 
X 
 
 
 
X 
X 
 
X 
X 
 
 
Adverse events 
 
Throughout Study 
Prior/Concomitant 
medications 
Xp 
Throughout Study 
CRU = clinical research unit; EOS = end-of-study; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; I/E = inclusion/exclusion; 
MAD = multiple ascending dose; PK = pharmacokinetic; QD = once daily; SAD = single ascending dose. 
a: Subjects will arrive at the CRU in the morning on Day -1 (approximately 24 hours before the planned first dose). For the Days 12, 20, and 32 check-ins/visits, 
the subject should arrive after an overnight fast of at least 10 hours (and before breaking the fast) and before taking study drug. On Days 6 and 60, the subject 
should not have any study drug in his/her possession and should arrive (in a fasted condition) in the morning (before the planned time of study drug dosing to 
be given in the clinic on Day 6 [no study drug dosing on Day 60]). 
b: Discharge from the 1st, 2nd, and 3rd (last) in-clinic periods will occur on Days 3, 13, and 34, respectively, after all procedures for that day are done and the last 
blood sample or urine collection for that in-clinic period is collected.  
c: The EOS visit will be scheduled for 28 (±2) days after the last dose of study drug in the MAD portion. 
d: All physical examinations will include weight; however, height will be measured only at screening.  
e: Vital signs will be measured at Screening, every check-in, every check-out, predose (within 60 min before the dose) and 4 hours (±10 minutes) after the dose 
on Days 1, 6, 12, 20, and 32, once daily on all other in-clinic days, and at the EOS visit. 
f: Electrocardiograms will be performed at Screening, Day -1 check-in, predose (within 60 min before the dose) and 2 hours (±10 minutes) after the dose on 
Days 1, 6, 12, 20, and 32, and at the EOS visit. 
g:  Samples for clinical safety laboratory tests (hematology, chemistry, coagulation, and urinalysis) will be collected under fasting conditions. 
h: Serum pregnancy tests at Screening, Day -1, and EOS visits; urine pregnancy tests at other time points. Also, female subjects claiming postmenopausal status 
will have that status verified with an FSH test at Screening. Once a female subject is verified as postmenopausal or otherwise not of childbearing potential, 
the subject is exempt for further pregnancy tests. On Days 6, 12, 20, and 32, the urine pregnancy test must be done (and the result negative) before study drug 
is administered. 
j: On Days 1, 6, 12, 13, 20, and 32, study drug will be administered at the clinic. All other doses of study drug will be taken at home QD with water in the 
morning (preferably after an overnight fast of ≥10 hours with the fast broken ≥2 hours after the dose). Study drug administration should be at approximately 
the same time of day (preferably 8 am) throughout the multiple dosing periods. See Section 6.7 for when study drug will be dispensed and/or collected. 
k: The 5-day washout between single and multiple dosing will start immediately after the Day 1 dose and end immediately before the Day 6 dose. There is no 
visit on Day 5; it is in the Schedule of Assessments only for depiction of the 5-day washout. 
l: For the Day 1 dose, blood samples for PK will be collected predose (within 60 minutes before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours 
(±5 minutes for all time points) after the dose. On Days 12 and 32, blood samples for PK will be collected predose (within 60 minutes before the dose) and at 
0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours (±5 minutes for all time points) after the dose. On Day 13, a blood sample for PK will be collected predose (i.e., at 24 hours 
±5 minutes after the Day 12 dose). On Day 33, blood samples for PK will be collected at 24 and 36 hours (±5 minutes for both time points) after the Day 32 
dose. On Day 34, a blood sample for PK will be collected at 48 hours (±5 minutes) after the Day 32 dose. 


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m: With the exception of the blood samples for biomarkers taken at Screening and Day -1, the time points and allowable windows for the blood samples for 
biomarkers will match those for the blood samples for PK. 
n: Urine for galactitol measurement will be collected over the 24 hours immediately before and the 24 hours immediately after the dose on Day 1. Urine for 
galactitol measurement will be collected over the 24 hours immediately after the dose on Days 12 and 32. For each collection of urine for galactitol 
measurement, an aliquot of the total urine collected will be analyzed for creatinine. Also, a spot collection for urine galactitol measurement will be taken at 
screening. 
o: Visit window +/- 1 day of scheduled visit for all visits except the EOS visit which has a window of +/- 2 days. 
p: These assessments must be performed on Day -1 even if they were already performed earlier during the screening period. 
 
 
 


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APPENDIX F. SCHEDULE OF ASSESSMENTS FOR PART D 
EXTENSION 


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Schedule of Assessments for the 90-day Extension in Subjects with Classic Galactosemia (Part D Extension)a 
PROCEDURE 
Prescreening 
Screening 
(Day -60 to -1)b 
Day -1c 
Day 1 
Day 2d 
Day 30c 
Day 60c 
Day 90c 
Day 91 
EOE Visite 
Day 118 
Check-in 
 
 
X 
 
 
 
 
X 
 
 
Discharge 
 
 
 
 
X 
 
 
 
X 
 
Informed consent 
 
Xf 
Xf 
 
 
 
 
 
 
 
I/E criteria 
 
X 
X 
 
 
 
 
 
 
 
Medical history/updates 
X 
(only CG 
diagnosis) 
X 
X 
 
 
 
 
 
 
X 
Demographic data 
 
Xq 
 
 
 
 
 
 
 
 
Physical examinationg 
X 
X 
X 
 
 
X 
X 
X 
 
X 
Vital signsh 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
Electrocardiogrami 
 
X 
X 
X 
 
X 
X 
X 
 
X 
Clinical laboratory testingj 
Xj 
Xj 
Xj 
 
 
X 
X 
X 
 
X 
GALT activity in red blood cells and 
GALT gene analysis 
Xq 
Xq 
 
 
 
 
 
 
 
 
Aldose Reductase activity 
 
Xq 
 
 
 
 
 
 
 
 
HIV and hepatitis B & C testingj 
X 
X 
 
 
 
 
 
 
 
 
Urine drug screen 
 
X 
X 
 
 
 
 
 
 
 
Pregnancy test (female subjects)k 
 
Xk 
Xk 
 
 
X 
X 
X 
 
X 
Drug administrationm 
 
 
 
X 
 
 
Blood sample collection for PK analysisn 
 
 
 
X 
 
X 
X 
X 
X 
 
Blood sample collectiono for galactose, 
galactitol, galactose-1-p and other 
galactose metabolites 
 
X 
 
X 
 
X 
X 
X 
X 
 
Urine sample for galactitolp 
X 
X 
 
 
 
 
 
 
 
 
Impact-of-disease interview 
 
 
 
X 
Adverse events 
 
 
 
Throughout Extension 
Prior/Concomitant medications 
 
X 
 
Throughout Extension 
CG = Classic Galactosemia; CRU = clinical research unit; EOE = end-of-extension; EOS = end-of-study; I/E = inclusion/exclusion; MAD = multiple ascending 
dose; PK = pharmacokinetic; QD = once daily. 


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a: All visits beyond Day 2 have visit windows of +/- 2 days. However, Day 1 must be the day of the first dose (in the extension); Day -1 must be the day before 
the first dose; Day 90 must be the day of the last dose; Days 88 and 89 must be the 2 days before day of the last dose; and Day 91 must be the day after the 
last dose. 
b: Screening visit for the Part D Extension is needed for subjects who have not previously participated in Part D. For subjects who previously participated in 
Part D, this Screening Visit is only needed if Day 1 of the extension period will be >60 days after the last visit (EOS or otherwise) in Part D. 
c: Check-in will occur around 11 am on Day -1. On Day 90, subjects will arrive at the CRU after an overnight fast of at least 10 hours (and before breaking the 
fast) and before taking study drug. In lieu of overnight stays in the CRU, subjects may stay at a local hotel; subjects will abide by all study guidelines 
including overnight fasting. The Day 30 and Day 60 visits can be either home health or in-clinic visits. 
d: Discharge from the in-clinic stay will occur after all procedures for that day are done and the subject has stayed in the clinic for at least 24 hours after the first 
dose.  
e: The EOE visit will be scheduled for 28 (±2) days after the last dose of study drug. The EOE Visit will not be required if subjects transition to the separate 
Open-Label Extenstion Study, in which case the study completion will be considered the completion of the Treatment Period at Day 91. 
f: The informed consent form needs to be signed at the first visit for the extension which may be either the Screening visit or the Day -1 check-in (see 
footnote b). 
g: All physical examinations will include weight; however, height will be measured only at screening (or prescreening). Prescreening does not include a physical 
examination (only height and weight). 
h: Vital signs will be measured at Screening (if applicable), every check-in, every check-out, predose (within 60 min before the dose) and 4 hours (±10 minutes) 
after the dose on Days 1, 30, 60, and 90, once daily on all other visits, and at the EOE visit. 
i: Electrocardiograms will be performed at Screening (if applicable), Day -1 check-in, predose (within 60 min before the dose) and 2 hours (±10 minutes) after 
the dose on Days 1, 30, 60, and 90, and at the EOE visit. 
j:  Samples for clinical safety laboratory tests (hematology, chemistry, coagulation, urinalysis, UACR and UPCR) will be collected under fasting conditions. At 
the Screening visit only (i.e., only applicable to subjects for whom this visit is required and does not need to be repeated at screening if already done at 
prescreening), HIV and hepatitis B & C testing will also be done. Hematology, chemistry, and coagulation at the Screening visit (i.e., only applicable to 
subjects for whom this visit is required) does not need to be repeated if already done at prescreening and prescreening was within 60 days before the first dose 
of Part D Extension study drug. Clinical safety laboratory tests (hematology, chemistry, coagulation, urinalysis, UACR and UPCR) do not need to be repeated 
at Day -1 if already done at prescreening or screening and the prescreening/screening visit was done within 60 days before the first dose of Part D Extension 
study drug. 
k: Serum pregnancy tests will be done at Screening (if applicable), Day -1 (also urine test if serum test cannot be processed immediately), and EOE visits; urine 
pregnancy tests will be done at all other time points. From Days 1 through 90, pregnancy tests must be done (and the result negative) on dosing days before 
study drug is administered. A pregnancy test must be performed on Day -1 even if already performed earlier during the screening period.  
m: On Days 1, 2, and 90, study drug will be administered at the clinic. On Days 30 and 60, study drug will be administered during the visit (home health or in-
clinic), All other doses of study drug will be taken at home QD with water in the morning (preferably after an overnight fast of ≥10 hours with the fast broken 
≥2 hours after the dose). Study drug administration should be at approximately the same time of day (preferably 8 am) throughout the extension. Drug 
accountability (including dispensing and/or collecting) will be assessed at all visits during the 90 days of dosing.  
n: On Day 1, a predose (within 60 minutes before the dose) blood sample for PK will be collected. On Days 30, 60, and 90, blood samples for PK will be 
collected predose (24 hours [±15 minutes] after the dose taken the day before and within 60 minutes before the dose administered on that day) and at 2, 4, 8, 
and 12 hours (±5 minutes for all time points) after the dose. An additional sample will be taken on Day 91 at 24 hour after the Day 90 dose. 
o: With the exception of the blood sample for biomarkers taken Screening (for those subjects requiring a screening visit), the time points and allowable windows 
for the blood samples for biomarkers will match those for the blood samples for PK. 


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p: Urine spot collection for galactitol analysis to check the study entry criterion based on urine galactitol (applicable only to subjects requiring a screening visit 
because it is assumed that urine galactitol for subjects not requiring the screening visit remain in the study eligible range and does not need to be repeated if 
done at prescreening)q: Required only for de novo subjects (i.e., subjects who did not previously participate in Part D SAD and MAD and does not need to be 
repeated at screening if already done at prescreening).  


Protocol AT-007-1001 Version 10.0 
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CONFIDENTIAL 
3 September 2021 
 
Page 116 of 120 
APPENDIX G. GUIDANCE IN CASE OF INCREASE IN ALT OR AST 
1. If ALT or AST > 3x ULN and Total Bilirubin < 2x ULN: 
• The event must be reported to the Sponsor within 24 hours. 
• The following laboratory tests will be performed: alkaline phosphatase, total and 
conjugated bilirubin, prothrombin time, international normalized ratio (INR), 
creatinine phosphokinase (CPK), serum creatinine, complete blood count, hepatitis A 
virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus 
(HDV), and hepatitis E virus (HEV). 
• Recent medical history will be investigated specifically for intercurrent illness, 
malaise with or without loss of consciousness, dizziness, hypotension, episodes of 
arrhythmia, and muscular injury. 
• Concomitant medications, including recreational drugs, nonprescription medications 
and herbal and dietary supplement preparations, will be reviewed and any substance 
potentially responsible for the elevation of liver enzymes will be discontinued, if 
possible 
• Information on potential exposure to environmental chemical agents, alcohol use, and 
special diets, including adherence to a galactose-restricted diet, will be collected and 
any factor potentially responsible for the elevation of liver enzymes will be 
addressed, if possible 
• If the patient is asymptomatic and the ALT/AST elevation is not associated with 
abnormal liver function (e.g. increased bilirubin or abnormal coagulation parameters), 
the STUDY TREATMENT WILL BE CONTINUED UNDER STRICT 
MONITORING as below. 
• Liver function tests (LFTs) will be monitored every two weeks x2 and then monthly 
for six months. If ALT or AST decrease to below 3x ULN, then monthly monitoring 
will continue until resolution. If ALT or AST increase to >5x ULN or if Total 
Bilirubin increases to >2x ULN, implement the below procedures. 
• For ALT or AST >3x ULN lasting six months, perform a hepatic ultrasound and 
consult with a hepatologist  
2. If ALT or AST > 5x ULN OR if ALT or AST >3x ULN and Total Bilirbuin >2x ULN, a retest 
must be performed within 24 hours 
2a. If confirmed ALT or AST > 5x ULN OR if ALT or AST >3x ULN and Total Bilirbuin >2x 
ULN:  
• The event must be reported to the Sponsor within 24 hours. 
• STUDY TREATMENT WILL BE DISCONTINUED. 
• The following laboratory tests will be performed: alkaline phosphatase, total and 
conjugated bilirubin, prothrombin time, international normalized ratio (INR), CPK, 


Protocol AT-007-1001 Version 10.0 
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CONFIDENTIAL 
3 September 2021 
 
Page 117 of 120 
serum creatinine, complete blood count, hepatitis A virus (HAV), hepatitis B virus 
(HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV) 
• A 2 mL serum sample will be collected and stored frozen for future analysis  
• An hepatobiliary ultrasonography will be performed.  
• All necessary investigations will be performed to rule out autoimmune or alcoholic 
hepatitis; non-alcoholic steatohepatitis (NASH); biliary tract disease, and 
hypoxic/ischemic hepatopathy (possibly due to right heart failure or other 
cardiovascular disease)  
• Recent medical history will be investigated specifically for malaise with or without 
loss of consciousness, dizziness, hypotension, episodes of arrhythmia, and muscular 
injury. 
• Concomitant medications, including recreational drugs, nonprescription medications 
and herbal and dietary supplement preparations, will be reviewed  
• Information on potential exposure to environmental chemical agents, alcohol use, and 
special diets, including adherence to a galactose-restricted diet, will be collected 
• A consult with an hepatologist will be requested. 
• Liver Function tests (LFTs) will continue to be monitored every 48 hours until 
stabilization and symptoms remission (if any), then every 2 weeks until 
normalization. 
2b. If ALT or AST > 5x ULN OR if ALT or AST >3x ULN and Total Bilirbuin >2x ULN not 
confirmed and ALT or AST is <5x ULN and > 3x ULN (with Total Bilirbuin <2x ULN) all the 
procedures listed above under section 1 will be implemented. 
 
2c. ALT or AST < 3x ULN but > 1.5x ULN: 
• The event must be reported to the Sponsor within 24 hours. 
• LFTs will continue to be monitored every month until normalization or further 
elevation. If ALT or AST > 3 x ULN, all the procedure above in section 1 will be 
implemented. If ALT/AST > 5x ULN, OR if ALT or AST >3x ULN and Total 
Bilirbuin >2x ULN, all the procedures listed above under section 2 will be 
implemented. 
 


Protocol AT-007-1001 Version 10.0 
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CONFIDENTIAL 
3 September 2021 
 
Page 118 of 120 
APPENDIX H. GUIDANCE IN CASE OF WORSENING RENAL 
FUNCTION 
Renal function must be closely monitored during the study, particularly during administration of 
potentially nephrotoxic drugs, such as acetaminophen, non-steroidal anti-inflammatory drugs 
(NSAIDs), fluoxetine, antihistamines, antimicrobials, benzodiazepines, proton pump inhibitors, 
phenytoin, trimethoprim, fenofibrate, cimetidine, cephalosporins, probenecid, aminoglycoside, 
amphotericin, ketoconazole, and clofibrate 
Urine protein-to-creatinine ratio (UPCR), urine albumin-to- creatinine ratio (UACR) and eGFR 
will be assessed at each visit. In case of increased UPCR (≥  200 mg/g), increased UACR (≥  30 
mg/g), eGFR < 30 mL/min/1.73 m2 , or decreased eGFR > 30% compared to baseline, a retest 
must be performed within 24 hours and if the abnormal laboratory result is confirmed, the 
following actions will be taken: 
• The event must be reported to the Sponsor within 24 hours  
• Concomitant medications will be reviewed and any potentially nephrotoxic drug must be 
discontinued 
• Recent medical history will be investigated specifically for significant increase or 
decrease of blood pressure, plasma volume depletion, flu-like symptoms, urinary tract 
infection, and abdominal pain suggestive of obstructive uropathy. 
• If there is no suspected concomitant medication , or if no improvement of renal function 
is observed after 72 hours of discontinuation of the potentially nephrotoxic drug, and if 
there is nothing in recent medical history that is likely to cause the abnormal renal 
function,  the study drug will be temporarily discontinued. 
• The following urinary  markers of kidney injury must be measured: Clusterin (CLU), 
Cystatin-C (CysC), Kidney Injury Molecule-1 (KIM-1), N-acetyl-beta-D-
glucosaminidase (NAG), Neutrophil gelatinase-associated lipocalin (NGAL), and 
Osteopontin (OPN) 
• A renal ultrasound  will be performed. 
• A nephrologist will be consulted 
• Renal function (eGFR, UPCR and UACR) will continue to be monitored every 48 hours 
until stabilization, then every 2 weeks until normalization.  
• At this time, the Investigator in consultation with the nephrologist will decide if the study 
drug may resume  
 


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CONFIDENTIAL 
3 September 2021 
 
Page 119 of 120 
APPENDIX I. RESULTS OF IN-VITRO DRUG-DRUG-INTERACTION (DDI) STUDIES WITH AT-007 
Recommendations related to the use of co-
medications 
Potential effect 
Rationale/Comments 
Reference 
CYP1A2 substrates - use with caution with sensitive 
substrates 
(Alosetron, caffeine, duloxetine, melatonin, 
ramelteon, tasimelteon, tizanidine) 
Increase in systemic exposure 
of sensitive substrates of 
CYP1A2 
Reversible inhibition was 
not significant (AUCR = 
1.03 for caffeine). TDI 
was observed with an IC50 
of 35.7 µM; however, KI 
and kinact could not be 
determined 
Study No.  
AACM-0014-
DV-TB, 
Study No. 
Applied-03 
 
CYP3A4 substrates - use with caution with sensitive 
substrates 
(Alfentanil, avanafil, buspirone, conivaptan, 
darifenacin, darunavir, ebastine, everolimus, 
ibrutinib, lomitapide, lovastatin, midazolam, 
naloxegol, nisoldipine, saquinavir, simvastatin, 
sirolimus, tacrolimus, tipranavir, triazolam, 
vardenafil, budesonide, dasatinib, dronedarone, 
eletriptan, eplerenone, felodipine, indinavir, 
lurasidone, maraviroc, quetiapine, sildenafil, 
ticagrelor, tolvaptan) 
Reduction in systemic 
exposure of sensitive 
substrates of CYP3A4 
CYP3A4 induction AUCR 
= 0.14, so significant 
using Mechanistic Static 
Model 
Study No. 
AACM-0015-
DV-DA 
 
Increase in systemic exposure 
of sensitive substrates of 
CYP3A4 
There was no TDI effect. 
AUCR was <1.66 (so 
>1.25), based on 
reversible IC50 of >100 
µM. However, IC50 would 
have to be ~800 µM for 
AUCR to be <1.25; 
inhibition at 100 µM was 
36.7% for midazolam and 
52.5% for testosterone, so 
there is negligible 
likelihood that the actual 
IC50 would be near 
800 µM 
Study No.  
AACM-0014-
DV-TB  


Protocol AT-007-1001 Version 10.0 
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CONFIDENTIAL 
3 September 2021 
 
Page 120 of 120 
Recommendations related to the use of co-
medications 
Potential effect 
Rationale/Comments 
Reference 
CYP2B6 substrates - use with caution with sensitive 
substrates 
(bupropion) 
 
 
Increase in systemic exposure 
of sensitive substrates of 
CYP2B6 
 
Reversible inhibition was 
not significant (AUCR = 
1.04 for bupropion). TDI 
was observed; AUCR 
including both reversible 
and TDI was 10.4 for 
bupropion, which is 
highly significant (>1.25). 
Study No.  
AACM-0014-
DV-TB, 
Study No. 
Applied-03 
 
CYP2C19 substrates - use with caution with 
sensitive substrates (omeprazole, S-mephenytoin) 
 
Increase in systemic exposure 
of sensitive substrates of 
CYP2C19 
Reversible inhibition was 
not significant (AUCR = 
1.07 for omeprazole). TDI 
was observed; AUCR 
including both reversible 
and TDI was 5.2 for 
omeprazole, which is 
highly significant (>1.25). 
Study No.  
AACM-0014-
DV-TB, 
Study No. 
Applied-03 
 
BCRP substrates. 
Use with caution with sensitive substrates of BCRP  
(rosuvastatin, sulfasalazine) 
Increase in systemic exposure 
of sensitive substrates of 
BCRP 
Potentially clinically 
relevant inhibition of 
BCRP observed with 
Igut/IC50 of 1200 
Study No.  
Applied-01-
11Jun2019 
BCRP inhibitors. 
Use with caution with potent inhibitors of BCRP  
(cyclosporine A) 
Increase in systemic exposure 
of AT-007 
AT007 observed to be a 
substrate of BCRP 
Study No.  
Applied-01-
11Jun2019 
OAT1, OAT3 substrates - use with caution with 
sensitive substrates 
(adefovir, cefaclor, ceftizoxime, famotidine, 
furosemide, ganciclovir, methotrexate, oseltamivir 
carboxylate, penicillin G)  
Increase in systemic exposure 
of sensitive substrates of 
OAT1 or OAT3 
Potentially clinically 
relevant inhibition of 
OAT1 (minor) and OAT3 
observed with Imax,u/IC50 
of 10.0 for OAT3 
Study No.  
Applied-01-
11Jun2019 
 

SAP_001.pdf: 
 
 
 
Page 1 of 1 
February 14, 2023 
 
To Whom It May Concern: 
This is the statistical analysis plan (SAP) for the below mentioned study. 
Study Title: A Phase 1-2, dose-escalating, 6-part study to evaluate the safety and pharmacokinetics 
and pharmacodynamics of single and multiple doses of AT-007 in healthy adult subjects and adult 
subjects with Classic Galactosemia (CG) or GALK Deficient Galactosemia 
 
NCT: NCT04117711 
 
Document Date of SAP: 20 July 2021 
 
Please contact me with any questions. 
 
Respectfully, 
 
 
Evan Bailey, MD 
Exective Clinical Director 
 
 
 
 
 
 
 
 
 


 
Applied Therapeutics Inc. 
Protocol No. AT-007-1001 
 
 
ICON Project No. 4848/0001 
Statistical Analysis Plan Final v3.0 
20 July 2021 
 
 
 
Page 1 of 71 
Confidential 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
 
 
A PHASE 1-2, DOSE-ESCALATING, 6-PART STUDY TO EVALUATE 
THE SAFETY AND PHARMACOKINETICS OF SINGLE AND 
MULTIPLE DOSES OF AT-007 IN HEALTHY ADULT SUBJECTS AND 
ADULT SUBJECTS WITH CLASSIC GALACTOSEMIA (CG) OR GALK-
DEFICIENT GALACTOSEMIA 
 
 
SAP Version 3.0 
FINAL 
Date: 20 July 2021 
 
for 
 
Protocol No. AT-007-1001 
 
 
Submitted to: 
Applied Therapeutics Inc. 
340 Madison Avenue | 19th Floor  
New York, NY 10173 
USA 
 
 
Prepared by: 
ICON Clinical Research, LLC 
820 West Diamond Avenue, Suite 100 
Gaithersburg, MD 20878 
Telephone: (301) 944-6800 
 
Fax: (215) 699-6288 
 
 
 
 
DocUUID : dee385e5-5ec3-4429-930f-f0e8534878d8


 
Applied Therapeutics Inc. 
Protocol No. AT-007-1001 
ICON Project No. 4848/0001 
Statistical Analysis Plan Final v3.0 
                                                                20 July 2021 
 
 
Page 2 of 71 
Confidential 
 
 
SIGNATURES 
ICON Development Solutions, LLC (ICON) Signature Page 
ICON Authors: 
 
 
 
 
 
 
 
 
Dipayan Maity 
Statistician I, Biostatistics 
 
Date 
ICON Reviewers: 
 
 
 
 
 
 
Geethalakshmi Gunasekaran 
Principal Biostatistician, Biostatistics 
 
 
Date 
 
 
 
 
Ganesh Munusamy 
Principal SAS Programmer , IEP Programming 
 
Date 
 
 
 
 
Laurie Reynolds 
Senior PK Scientist II, IEP Pharmacokinetics 
 
Date 
 
ICON Approvals: 
 
 
 
 
Colm Farrell 
Sr Director, Pharmokinetics, IEP Pharmacokinetics 
 
Date 
 
 
 
DocUUID : dee385e5-5ec3-4429-930f-f0e8534878d8
db176dec-b675-4a8e-8604-b1ce75c558d1
Geethalakshmi Gunasekaran
20 Jul 2021 12:34:009+0000
REASON: I approve this document
6b0f2146-272f-408a-ac3a-d291525950f9
Dipayan Maity
20 Jul 2021 12:36:040+0000
REASON: I approve this document
3ae89d69-8d9e-4922-815b-1809d52f30aa
Ganesh Munuswamy
20 Jul 2021 13:17:031+0000
REASON: I approve this document
d6ad1f2c-7b30-4b99-ad94-1e44ce82e6be
Laurie Reynolds
20 Jul 2021 14:10:054+0000
REASON: I approve this document
b5383b1b-f645-4a48-be75-b3ed19d2aac8
Colm Farrell
21 Jul 2021 15:04:044+0000
REASON: I approve this document


 
Applied Therapeutics Inc. 
Protocol No. AT-007-1001 
ICON Project No. 4848/0001 
Statistical Analysis Plan Final v3.0 
                                                                20 July 2021 
 
 
Page 3 of 71 
Confidential 
 
 
Applied Therapeutics Inc. Signature Page 
 
Applied Therapeutics Inc. Approvals: 
 
 
 
 
 
 
Riccardo Perfetti, MD, PhD 
Chief Medical Officer, Applied Therapeutics Inc. 
 
 
 
Date 
 
 
 
DocUUID : dee385e5-5ec3-4429-930f-f0e8534878d8
7/21/2021


 
Applied Therapeutics Inc. 
Protocol No. AT-007-1001 
ICON Project No. 4848/0001 
Statistical Analysis Plan Final v3.0 
                                                                20 July 2021 
 
 
Page 4 of 71 
Confidential 
 
 
REVISION HISTORY 
Version 
Date 
Author 
Comments 
Final V1.0 
03DEC2019 
Shekar Sunkoju 
Initial document 
Final V2.0 
14JULY2020 
Shekar Sunkoju 
Added Part D Extension and E. 
Final V3.0 
20JUL2021 
Dipayan Maity 
• 
Addressed client comments on 
25May2021: 
o 
Updated Enzyme activity 
categories. 
o 
Added forest plot for 
Subgorup analysis of  
blood Galactitol. 
• 
Update Biomarker section 7.11 and 
LOT for biomarker related tables. 
 
DocUUID : dee385e5-5ec3-4429-930f-f0e8534878d8


 
Applied Therapeutics Inc. 
Protocol No. AT-007-1001 
ICON Project No. 4848/0001 
Statistical Analysis Plan Final v3.0 
                                                                20 July 2021 
 
 
Page 5 of 71 
Confidential 
 
 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation or Specialist 
Term 
Explanation 
AE 
adverse event 
Aet1-t2 
amount of unchanged drug excreted though urine 
ALT 
alanine transaminase 
ALP 
alkaline phosphatase 
ALT 
alanine transaminase 
AST 
aspartate transaminase 
AUC 
area under the concentration-time curve 
AUCinf 
Area under the concentration time curve from time zero 
extrapolated to infinity 
AUClast 
Area under the concentration time curve from time zero to 
the time of the last quantifiable concentration; calculated 
using the linear trapezoidal rule 
AUCtau 
area under the concentration-time curve within the dosing 
interval 
AUCExtrap (%) 
percentage of AUCinf based on extrapolation 
BLQ 
below the quantifiable limit 
BUN 
blood urea nitrogen 
CI 
confidence interval 
CL/F 
Clearance after extravascular administration 
CG 
classic galactosemia 
Clast 
last quantifiable concentration determined directly from 
individual concentration time data 
Cmax 
maximum concentration, determined directly from 
individual concentration time data 
CLR 
renal clearance  
CRA 
clinical research associate 
CRU 
clinical research unit 
CSF 
cerebrospinal fluid 
CSR 
clinical study report 
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Applied Therapeutics Inc. 
Protocol No. AT-007-1001 
ICON Project No. 4848/0001 
Statistical Analysis Plan Final v3.0 
                                                                20 July 2021 
 
 
Page 6 of 71 
Confidential 
 
 
Abbreviation or Specialist 
Term 
Explanation 
Ctrough 
trough or predose concentration 
CV 
coefficient of variation 
DLT 
dose limiting toxicity 
DMP 
Data Management Plan 
ECG 
Electrocardiogram 
eCRF 
electronic case report form(s) 
EOE 
end of extension  
EOS 
end-of-study 
fet1-t2 
fraction of the administered dose excreted in urine over the 
interval from time t1 to time t2 
FSH 
follicle-stimulating hormone 
fu/f 
fraction of orally administered drug excreted into urine 
GALK 
Galactokinase 
GALT 
galactose-1-phosphate uridylyltransferase 
HIV 
human immunodeficiency viruses 
HR 
heart rate 
ICH 
international council for harmonisation 
IEC 
Independent Ethics Committees 
IRB 
institutional review board 
LLQ 
lower limit of quantitation 
MAD 
multiple ascending dose 
MRS 
magnetic resonance spectroscopy 
MTD 
maximum tolerated dose 
OTC 
over the counter  
PK 
pharmacokinetic(s) 
PT 
preferred term 
QD 
once daily 
QT 
ECG interval between the start of the Q wave and the end 
of the T wave 
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Applied Therapeutics Inc. 
Protocol No. AT-007-1001 
ICON Project No. 4848/0001 
Statistical Analysis Plan Final v3.0 
                                                                20 July 2021 
 
 
Page 7 of 71 
Confidential 
 
 
Abbreviation or Specialist 
Term 
Explanation 
QTcF 
ECG interval between the start of the Q wave and the end 
of the T wave corrected for heart rate using Fridericia’s 
formula 
Rac 
accumulation ratio 
RBC 
red blood cell 
SAD 
single ascending dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SOC 
system organ class 
SP 
safety population 
SRC 
safety review committee 
t1/2 
terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
Tlast 
time of the last quantifiable concentration 
Tmax 
time of the maximum concentration 
Vz/F 
apparent volume of distribution during terminal phase  
Λz 
The observed terminal rate constant; estimated by linear 
regression through at least 3 data points in the terminal 
phase of the log concentration time profile 
 
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Applied Therapeutics Inc. 
Protocol No. AT-007-1001 
ICON Project No. 4848/0001 
Statistical Analysis Plan Final v3.0 
                                                                20 July 2021 
 
 
Page 8 of 71 
Confidential 
 
 
TABLE OF CONTENTS 
 
SIGNATURES................................................................................................................................2 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................................5 
TABLE OF CONTENTS ..............................................................................................................8 
1 
INTRODUCTION .......................................................................................................11 
2 
STUDY OBJECTIVES AND ENDPOINTS .............................................................12 
2.1 
Primary Objective ................................................................................................12 
2.2 
Secondary Objectives...........................................................................................12 
2.3 
Exploratory Objectives ........................................................................................12 
2.4 
Primary Endpoints...............................................................................................12 
2.5 
Secondary Endpoints ...........................................................................................12 
2.6 
Exploratory Endpoints ........................................................................................13 
3 
STUDY DESIGN .........................................................................................................14 
3.1 
General ..................................................................................................................14 
3.1.1 
Study Population ....................................................................................................17 
3.1.2 
Evaluations at Screening and Check-in .................................................................17 
3.1.3 
Randomization and Treatment Assignments .........................................................20 
3.1.4 
Study Drug Administration ....................................................................................21 
3.1.5 
Concomitant Medications ......................................................................................27 
3.1.6 
Treatment Compliance ...........................................................................................29 
3.1.7 
Pharmacokinetic Sampling Schedule .....................................................................29 
3.1.8 
Evaluation of Biomarkers ......................................................................................31 
3.2 
Evaluation of Treatment Safety ..........................................................................31 
3.2.1 
Adverse Events ......................................................................................................31 
3.2.2 
Clinical Laboratory Assessments ...........................................................................31 
3.2.3 
Vital Signs ..............................................................................................................33 
3.2.4 
Electrocardiograms ................................................................................................34 
3.2.5 
Physical Examinations ...........................................................................................34 
3.2.6 
Other Safety Assessments ......................................................................................35 
3.2.7 
Protocol Deviation Reporting ................................................................................35 
4 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED 
ANALYSIS ..................................................................................................................36 
5 
QUALITY CONTROL AND QUALITY ASSURANCE METHODS FOR 
DATA ANALYSIS ......................................................................................................37 
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Statistical Analysis Plan Final v3.0 
                                                                20 July 2021 
 
 
Page 9 of 71 
Confidential 
 
 
6 
PHARMACOKINETIC ASSESSMENTS ................................................................38 
6.1 
Pharmacokinetic Assessments ............................................................................38 
6.1.1 
Pharmacokinetic Analysis ......................................................................................38 
6.1.2 
Treatment of Outliers .............................................................................................41 
6.1.3 
Non-Quantifiable Concentrations ..........................................................................42 
7 
STATISTICAL METHODS ......................................................................................43 
7.1 
General ..................................................................................................................43 
7.2 
Handling of Dropouts or Missing Data ..............................................................44 
7.3 
Multicenter Studies ..............................................................................................44 
7.4 
Examination of Subgroups ..................................................................................44 
7.5 
Analysis Populations ............................................................................................44 
7.6 
Subject Accountability.........................................................................................45 
7.7 
Drug Exposure and Compliance.........................................................................45 
7.8 
Protocol Deviation Reporting .............................................................................46 
7.9 
Subject Demographics and Baseline Characteristics .......................................46 
7.10 
Analysis of Pharmacokinetic Data .....................................................................46 
7.11 
Analysis of Biomarker Data ................................................................................47 
7.12 
Analysis of Safety Data ........................................................................................48 
7.12.1 
General ...................................................................................................................48 
7.12.2 
Adverse Events ......................................................................................................48 
7.12.3 
Clinical Laboratory Assessments ...........................................................................49 
7.12.4 
Vital Signs ..............................................................................................................50 
7.12.5 
Electrocardiograms ................................................................................................50 
7.12.6 
Physical Examinations ...........................................................................................50 
7.12.7 
Prior and Concomitant Medications ......................................................................50 
7.13 
Sample Size ...........................................................................................................50 
7.14 
Interim Analysis ...................................................................................................51 
7.15 
General Conventions for Tables, Listings and Figures ....................................52 
8 
TABLES, FIGURES, AND LISTINGS.....................................................................53 
 
 
 
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Applied Therapeutics Inc. 
Protocol No. AT-007-1001 
ICON Project No. 4848/0001 
Statistical Analysis Plan Final v3.0 
                                                                20 July 2021 
 
 
Page 10 of 71 
Confidential 
 
 
Table of Tables 
 
Table 3-1:  
Study Design .........................................................................................................14 
Table 3-2: 
SAD Dose Cohorts in Healthy Subjects (Part A) ..............................................22 
Table 3-3: 
MAD Dose Cohorts in Healthy Subjects (Part B) .............................................23 
Table 3-4: 
MAD Dose Cohorts in Healthy Subjects with CSF Collection 
(Part C) .................................................................................................................23 
Table 3-5: 
SAD and MAD Dose Cohorts in Subjects with Classic 
Galactosemia (Part D) .........................................................................................24 
Table 3-6: 
Dose Cohort in Subjects with GALK-deficient Galactosemia 
(Part E) ..................................................................................................................25 
Table 3-7:  
90-Day Dose Cohort in Subjects with Classic Galactosemia 
(Part D Extension)................................................................................................26 
Table 6-1: 
Pharmacokinetic Parameters of AT-007 After a Single Dose in 
Healthy Subjects (Part A) and Subjects with Classic 
Galactosemia (Single Ascending Dose Period of Part D and E) ......................39 
Table 6-2: 
Pharmacokinetic Parameters of AT-007 During Multiple 
Dosing in Healthy Subjects (Parts B and C) and Subjects with 
Galactosemia (Multiple Ascending Dose Period of Parts D and 
E and Part D Extension) ......................................................................................40 
Table of Figures 
Figure 1: 
Study Schematic.....................................................................................................15 
 
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Applied Therapeutics Inc. 
Protocol No. AT-007-1001 
ICON Project No. 4848/0001 
Statistical Analysis Plan Final v3.0 
                                                                20 July 2021 
 
 
Page 11 of 71 
Confidential 
 
 
1 
INTRODUCTION 
This statistical analysis plan (SAP) is consistent with the statistical methods section of the final 
study protocol (Version 6.0, dated 05 May 2020) and includes additional detail of 
pharmacokinetic (PK) and safety summaries to be included in the clinical study report (CSR). 
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2 
STUDY OBJECTIVES AND ENDPOINTS 
2.1 
Primary Objective 
• To evaluate the safety of single and multiple ascending doses of orally administered 
AT-007 in healthy adult subjects and adult subjects with CG or GALK-deficient 
Galactosemia 
2.2 
Secondary Objectives 
• To evaluate the pharmacokinetic (PK) parameters of single and multiple doses of orally 
administered AT-007 in healthy adult subjects and adult subjects with CG or GALK-
deficient Galactosemia 
• To evaluate the effect of single and multiple doses of orally administered AT-007 on the 
level of galactitol, a biomarker of aldose reductase (AR) activity, in adult subjects with 
CG or GALK-deficient Galactosemia 
• To evaluate the effect of single and multiple doses of orally administered AT-007 on the 
levels of galactose and its other metabolites in adult subjects with CG or GALK-deficient 
Galactosemia 
 
2.3 
Exploratory Objectives 
• To measure the levels of AT-007 in the cerebrospinal fluid (CSF) of healthy adult 
subjects  
2.4 
Primary Endpoints 
The primary endpoints of this study are overall safety and adverse events (AEs). Safety will be 
assessed by the following endpoints: 
• AEs 
• Clinical safety laboratory tests (hematology, chemistry, urinalysis) 
• Physical examinations 
• Vital signs 
• Electrocardiograms (ECGs) 
2.5 
Secondary Endpoints 
The secondary endpoints are the following: 
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• PK parameters in healthy subjects, subjects with CG, and subjects with GALK-deficient 
Galactosemia 
• Galactitol galactose and its other metabolites   in the blood of subjects with CG and 
subjects with GALK-deficient Galactosemia 
• Urine galactitol for subjects with CG and subjects with GALK-deficient Galactosemia 
2.6 
Exploratory Endpoints 
The exploratory endpoints are the following: 
• AT-007 level in the CSF of healthy subjects (Part C only) 
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3 
STUDY DESIGN 
3.1 
General 
This study is a first-in-human, randomized, placebo-controlled, 6-Part, single ascending dose 
(SAD) and multiple ascending dose (MAD) study in healthy adult subjects, adult subjects with 
CG, and adult subjects with GALK-deficient Galactosemia. The study is designed to assess the 
safety and PK (including metabolites) of AT-007 in these subjects as well as the effect of AT-
007 on biomarkers of galactose metabolism (galactose, and galactose metabolites) in subjects 
with galactosemia. The study is being conducted in multiple centers in the US and Europe. 
This study consists of 6 parts with the timing of the parts (shown in Table 3-1 and Figure 1): 
Table 3-1:  
Study Design  
Study 
Part 
 
Study Population 
 
Design 
Planned 
Number 
of 
Cohorts 
Subjects Per 
Cohort 
Total # 
of 
Subjects 
Part A 
Healthy Adult Subjects 
SAD 
5 
8 
40 
Part B 
Healthy Adult Subjects 
MAD (QD for 7 days) 
4 
6 in 2 cohorts & 8 
in 2 cohorts 
28 
Part C 
Healthy Adult Subjects 
MAD (QD for 7 days) 
3 
4 
12 
Part D 
Adult Subjects with CG 
SAD, 5-day washout, 
MAD (QD for 27 days) 
3 
6 
18 
Part E 
Adult Subjects with 
GALK-deficient 
Galactosemia 
SAD, 5-day washout, 
MAD (QD for 27 days) 
1 to 3 
6 
18 
Part D 
Extension 
Adult Subjects with CG 
MAD (QD for 90 Days) 
1 to 2 
8 to 16 
16 
CG = Classic Galactosemia; MAD = multiple ascending dose; QD = once daily (dosing); SAD = single 
ascending dose. 
 
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Figure 1: 
Study Schematic 
 
 
Within each Part, the Cohorts are sequential. Solid lines with arrows indicate that data from the part or cohort at the 
non-arrow end are required before the part or cohort at the arrow end can start. Dotted lines indicate cohorts (C1 and 
B3; C3 and B4) that will be conducted simultaneously. Parts D, E, and D Extension are not dependent on Part C 
results, and no temporal relationship between Parts D, E, and D Extension and Part C is implied. Also, with the 
exception of Cohorts B4, C3, D3, E2, E3, and DE2 being directly or indirectly dependent on Cohort A5 results, no 
temporal relationship between Cohort A5 and any other part/cohort is implied. Cohort DE2 (start and dose level) are 
not dependent on results from Cohort DE1. 
For all cohorts in all parts (A, B, C, D, E, and D Extension), the study consists of a Screening 
Period (28 days [Day -28 to Day -1] in Parts A, B, and C and 40 days [Day -40 to Day -1] in Part 
D and E [and D Extension for de novo subjects who did not participate in Part D and subjects 
whose last visit in Part D was >40 days before Day 1 in the Part D Extension]), a period of study 
treatment and associated assessments, and an End-of-Study (EOS) Visit (28 days after the last 
dose of study drug) (for Part D Extension, the visit at 28 days after the last dose is called the end 
of extension [EOE] Visit). Subjects will be randomized and receive the first dose of study drug 
on Day 1. At a minimum, subjects will remain at the clinical research unit (CRU) through 24 
hours after the first dose. Subjects in Part A have one in-clinic stay during the Treatment Period 
and will receive the single dose in the CRU. Subjects in Parts B and C have 1 in-clinic stay with 
all 7 doses taken in the CRU. Subjects in Part D and E have 3 in-clinic stays with most doses 
taken at home. Subjects in Part D Extension will have 2 in-clinic stays and monthly out-patient 
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visits with most doses taken at home. Subjects who withdraw or are withdrawn from the study 
after taking study drug will not be replaced.  
Safety will be monitored and blood samples will be collected for PK in all parts of the study. 
Also, subjects in the selected dose cohorts of Parts A (SAD) and D (SAD portion only) will have 
urine collected for PK. In addition, subjects in Part C will have 1 lumbar puncture for CSF 
collection. Also, subjects in Part D and E will have blood samples and urine collected for 
biomarkers of galactose metabolism.  
The starting dose in Part A was 0.5 mg/kg as a single dose. Subsequent doses in Part A and all 
doses in Parts B, C, D, and E are based on the results of previous cohorts and/or previous parts of 
the study. Part A of the study started first. Part A Cohort 5 (40 mg/kg single dose) was recently 
added to the protocol (version 4.0) and results showed the dose was safe and well tolerated. Part 
B started after all subjects in Cohorts A1 through A4 completed the study (minus the EOS Visit). 
Given that the results for 40 mg/kg in Cohort A5 were acceptable, Part B Cohort 4 (40 mg/kg) 
will start with this version of the protocol (version 5.0). The first cohort in Part C (C1) started 
after both safety and PK data from Cohorts B1 and B2 were reviewed. Cohort C1 was conducted 
simultaneously with Cohort B3 and used the same dose as Cohort B2 (10 mg/kg). The second 
cohort in Part C (C2) started after safety and PK data from Cohort B3 were reviewed and used 
the same dose as Cohort B3 (20 mg/kg); safety and PK results for Cohort C1 were also 
considered before starting Cohort C2. The third cohort in Part C (C3) will start with this version 
of the protocol (version 5.0) and use the same dose as Cohort B4 (given the results from Cohort 
A5); safety and PK results for Cohort C2 were also considered before starting Cohort C3. The 
first cohort in Part D (D1) started after all subjects in Cohorts A1 through A4 completed the 
study including the EOS Visit and all subjects in Cohorts B1 and B2 completed the study (minus 
the EOS Visit). The dose for Cohort D1 (5 mg/kg) was not higher than the dose for Cohort B2 
(10 mg/kg). The second cohort in Part D (D2) started after all subjects in Cohort B3 completed 
the study (minus the EOS Visit) and the dose level (20 mg/kg) was the same as that for Cohort 
B3. The third cohort in Part D (D3) will start after all subjects in Cohort B4 complete the study 
(minus the EOS Visit) and the dose level will not be higher than the 40 mg/kg dose used for 
Cohort B4. The starting dose for Part E (Cohort E1) will be the most clinically appropriate dose 
as determined by the evaluation of available safety, tolerability, and PD (reduction in galactitol 
level) in Part D and the dose will not be higher than the highest acceptable dose in Part D at the 
time of starting Part E (after all subjects complete Cohorts D1 and D2 but may be before, during, 
or after Cohort D3). The Safety Review Committee (SRC) reviewed/will review safety data 
before each dose escalation and before the start of Parts B, C, D, and E. Also, the Sponsor 
reviewed/will review all PK and galactitol data as they become available. 
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The dose for the first cohort of the Part D Extension (DE1) will be 20 mg/kg/day based on 
acceptable SAD and MAD safety and PK data from Cohort D2. After SRC review of all SAD 
and MAD data and Sponsor review of PK and galactitol data for Cohorts D1 through D3, a 
second cohort of the Part D Extension (DE2) may be initiated to evaluate a dose higher than 20 
mg/kg/day if this dose was well tolerated in the SAD and MAD portions of the study in both 
healthy volunteers and subjects with CG.  
The review of the PK data from Cohorts A1 through A4 and the first 2 cohorts of Part B 
confirmed that once daily (QD) dosing is adequate.  
3.1.1 
Study Population 
For Parts A, B, and C - The study population will include healthy male or non-pregnant, non-
lactating female adult between 18 and 65 years of age, inclusive. 
For Part D and D Extension - Male and non-pregnant, non-lactating female adult between the 
ages of 18 and 65 years, inclusive, with a Classic Galactosemia (CG) diagnosis confirmed by 
evidence of absent or significantly decreased (<1%) galactose-1-phosphate uridylyltransferase 
(GALT) activity in red blood cells and by historical record of diagnosis of GALT deficiency 
(medical record or gene analysis report or written communication by health care professional), 
and who have no other significant health problems unrelated to CG. 
For the Part D Extension, subjects who previously participated in but did not complete Part D 
must not have discontinued Part D because of study drug related TEAE(s). 
3.1.2 
Evaluations at Screening and Check-in 
3.1.2.1 
Screening Evaluations 
The screening visit must occur within 28 days before the first dose of study drug for Parts A, B, 
and C and within 40 days before the first dose of study drug for Part D, E and D Extension.   
The Part D Extension screening visit is only applicable to the following subjects: 
• De novo subjects  
• Subjects whose last visit in Part D was >40 days before Day 1 in Part D Extension 
Part D Extension subjects who previously participated in Part D and had a last Part D visit within 
40 days before Day 1 of the extension do not need a screening visit for the extension. 
Subjects will be evaluated at the screening visit to determine their eligibility to enroll in the 
study. The following procedures will be done at screening: 
• Obtain signed informed consent from the subject and from the subject’s caregiver/LAR 
(if applicable) 
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The informed consent documents will be discussed with each potential subject and 
caregiver/LAR (if applicable), and each potential subject (and caregiver/LAR if 
applicable) will sign the informed consent form(s), as appropriate, for the study prior to 
any study-specific procedures being performed. 
• Review inclusion/exclusion criteria 
• Obtain medical history (including current medication)  
• Obtain demographic data (not necessary for Part D subjects being re-screened for Part D 
Extension) 
• Perform physical examination including height and weight 
• Measure vital signs  
• Conduct 12-lead ECG 
• Collect fasting blood sample(s) for clinical laboratory testing (hematology, coagulation 
and biochemistry); serology testing (screening for HIV, hepatitis B, and hepatitis C); and, 
for female subjects of childbearing potential only, serum pregnancy test (also follicle-
stimulating hormone (FSH) test for female subjects claiming postmenopausal status) 
• Collect fasting urine sample for urinalysis and drugs of abuse screen (also cotinine screen 
for subjects in Parts A, B, and C only) 
For Part D, E and D Extension only, the following procedures will be done in addition to the 
ones listed above: 
• Collect blood sample for assessment of GALT activity in red blood cells and GALT or 
GALK gene analysis (GALT for Parts D and D Extension and GALK for Part E) 
• Collect blood sample for assessment of aldose reductase activity 
• MRI/MRS of the brain if the subject and caregiver/LAR have consented to the brain 
imaging 
• Collect blood sample for analysis of biomarkers of galactose metabolism including 
galactose, galactitol, and galactose-1-p 
• Collect urine sample (spot collection) for analysis of galactitol 
Note: For Part D Extension subjects who were previously screened for Part D but had the last 
Part D visit >40 days before Day 1 in the extension, GALT and aldose reductase activity 
assessments do not need to repeated. The MRI/MRS of the brain will be done at the Part D 
Extension screening visit for these subjects only if they did not consent for it in Part D (hence, no 
baseline scan during Part D screening) but consented for it in Part D Extension. If they consented 
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for the brain scan in both Part D and Part D Extension, then the screening MRI/MRS was done 
during the Part D screening visit and does not need to be repeated. 
Subjects who are taking any disallowed medication(s) but otherwise eligible for the study may 
washout their disallowed medications (washout of at least 5 half-lives of the disallowed 
medication with the longest half-life). After the washout period, they may be rescreened. 
Eligible subjects will be contacted to inform them of their eligibility and schedule the start of 
study drug dosing for those wishing to continue in the study. Subjects (and caregivers if 
applicable for Part D Extension) in Parts A, B, C and D Extension will be instructed to arrive at 
the CRU at approximately 11 am on the day before the scheduled first dose of study drug. 
Subjects/Caregivers in Part D will be instructed to arrive at the CRU in the morning on the day 
before the scheduled first dose of study drug (ie, approximately 24 hours before the first dose).  
3.1.2.2 
Check-in Evaluations 
Subjects will arrive at the CRU at approximately 11 am (Parts A, B, C, and D Extension) or 
sometime in the morning (Part D and E [approximately 24 hours before the first dose]) on the 
day before the scheduled first dose of study drug. The following procedures will be done: 
• For Part D Extension subjects who did not have a Part D Extension screening visit only, 
obtain signed informed consent from the subject and from the subject’s caregiver/LAR (if 
applicable) 
• Review of inclusion/exclusion criteria 
• Obtain updates, if any, for medical history  
• Perform physical examination including weight 
• Measure vital signs  
• Conduct 12-lead ECG 
• Collect fasting blood sample(s) for clinical laboratory testing (hematology, coagulation 
and biochemistry); and, for female subjects of childbearing potential only, serum 
pregnancy test (pregnancy test must be negative for the subject to receive study drug) 
• Collect fasting urine sample for urinalysis and drugs of abuse screen (also cotinine screen 
for subjects in Parts A, B, and C only) 
• Collect AE and concomitant medication data 
• Feed the subject (2 meals [lunch and dinner]) 
• Fast the subject overnight for at least 10 hours 
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For Part D and E only, the following procedures will be done in addition to the ones listed above: 
• Collect blood sample for analysis of biomarkers of galactose metabolism including 
galactose, galactitol, and galactose-1-p. 
•  Collect urine over 24 hours (morning of Day -1 to immediately before the first dose [Day 
1]) for analysis of galactitol 
• Feed the subject (2 to 3 meals depending on check-in time) 
Subjects who no longer fulfill all inclusion criteria and/or now fulfill one or more exclusion 
criteria will be discontinued from the study and sent home. These subjects will be replaced. 
Subjects who continue to fulfill all inclusion criteria and none of the exclusion criteria will 
continue in the study. 
3.1.3 
Randomization and Treatment Assignments 
Subjects will be randomly assigned to either AT-007 or matching placebo in Parts A, B, D, E and 
D Extension. The number of subjects to be treated with AT-007 and the number of subjects to be 
treated with placebo in each cohort are described in Section 3.1.4. Subjects will be assigned to 
open-label AT-007 in Part C. 
Up to 116 subjects are planned to be dosed in this study: 
• Part A: 5 cohorts of 8 healthy subjects each 
• Part B: 2 cohorts of 6 healthy subjects each and 2 cohorts of 8 healthy subjects each  
• Part C: 3 cohorts of 4 healthy subjects each 
• Part D: 3 cohorts of 6 subjects with CG each 
• Part E: 1 to 3 cohorts of 6 subjects with GALK-deficient Galactosemia each 
• Part D Extension: 1 to 2 cohorts with a combined total of 16 subjects with CG 
The number of cohorts and total number of subjects may increase if doses above 40 mg/kg are 
tested in additional cohorts. 
In Parts A, B, D, E and D Extension, subjects will be randomized to receive either active drug 
(AT-007) or placebo. Each subject will receive an assigned treatment based on the randomization 
schedule prepared by the study statistician.  
Parts A and B will be double-blinded (the Sponsor/ CRO, clinical site staff [except for unblinded 
pharmacist for Parts A and B], and the subjects will not know which subjects are treated with 
AT-007 or placebo). 
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In Part C, all subjects will be assigned to receive active drug (AT-007). Part C will be open-label. 
In Parts D, E and D Extension the clinical site staff [except for the unblinded pharmacist], and 
the subjects will be blinded to study treatment. The Sponsor/CRO will not be blinded to study 
treatment in Part D, as the relationship between exposure in Parts D, E and D Extension (subject 
with galactosemia) vs. exposure in healthy subjects will need to be evaluated on an ongoing basis 
to ensure that AT007 blood level remain within the limits achieved in Part B. This process will 
minimize the number of subjects with galactosemia potentially exposed to plasma concentrations 
of AT-007 not previously tested and shown to be safe in healthy subjects.  
3.1.4 
Study Drug Administration 
Parts A, B, C, and D of the study will start more or less sequentially followed by starting Parts E 
and D Extension more or less concurrently. However, conduct of all study parts will overlap.  
Within each part, the cohorts (dose levels) will be dosed sequentially. The SRC will review 
available safety data through a pre-specified timeframe (Day 3 for Part A, Day 8 for Parts B and 
C, and Day 12 for Part D [and E, if applicable]) and provide recommendations for the next 
cohort. If there is a second cohort in Part D Extension, the dose will be higher than 20 mg/kg and 
depend on the results for that dose in healthy subjects and subjects with CG in Part D. Additional 
cohorts will be enrolled if it is deemed appropriate after safety assessment by the SRC and 
confirmation by the Sponsor. A decision to repeat a dose level or to study another higher or 
lower dose level may be made. The Investigator(s) and Institutional Review Boards (IRBs) / 
Independent Ethics Committees (IECs) will be notified of these decisions.  
The SRC will also review data for the last cohort for each study part except that there will be no 
next cohort within the same part of the study. 
AT-007 dose levels in Part A were between 0.5 and 40 mg/kg. Dose levels in subsequent parts of 
the study are based on the safety and pharmacokinetic results (and galactitol results in Parts D, E 
and D Extension only) of previous cohorts and/or previous parts of the study. Doses higher than 
40 mg/kg may be evaluated if the human Cmax and AUC are substantially lower than the 
corresponding values calculated in nonclinical experiments and no dose limiting toxicity is 
observed up to and including at the 40 mg/kg dose. If dose escalation above 40 mg/kg is feasible 
based on the above criteria, these higher doses may be investigated in additional SAD and MAD 
cohorts in healthy subjects and in subjects with CG or GALK-deficient Galactosemia if no AT-
007 levels are detected in the CSF collected from the healthy subjects enrolled in Cohort C3.  
For Parts A, B, and C, subjects will take the study drug (oral capsules of AT-007 or placebo) in 
the CRU under the supervision of study personnel. Study staff will conduct a hand and mouth 
check immediately after dose to ensure that the medication has been appropriately swallowed. 
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Most study drug doses in Parts D, E and D Extension subjects will be taken on an out-patient 
basis (ie, at home). Each subject will be provided with a diary card to record the dates/times for 
all doses taken at home.  
All doses of study drug should be taken under fasting conditions. Subjects should take all doses 
of study drug in the morning (with water) after overnight fasts of at least 10 hours. Subjects may 
end their fast at any time ≥2 hours after taking the study drug. These conditions are mandatory 
for doses associated with PK sampling and recommended for all other doses regardless of 
whether taken at home or in the clinic.  
3.1.4.1 
Part A: Double-blind SAD, Healthy Subjects 
Four dose levels were initially planned for the SAD group and a fifth dose level was recently 
added and completed (Table 3-2). Subjects were enrolled in 5 sequential cohorts of 8 subjects 
each, for a total of 40 subjects. The first cohort included a sentinel group (first 2 subjects with 1 
per treatment) dosed at the same time. Dose administration for the remainder of the first cohort 
occurred only at least 24 hours after the 2 sentinel subjects received study drug (AT-007 or 
placebo) and were contingent upon acceptable safety results through 24 hours for the sentinel 
subjects per Investigator in consultation with the Sponsor and with explicit agreement from the 
Sponsor. Subjects were housed at the CRU for observation for at least 48 hours after dosing. 
Subjects returned for the EOS Visit at 28 days after the dose. Progression to and the dose level 
for the next cohort were dependent upon safety data through Day 3 from the previous cohort.  
Table 3-2: 
SAD Dose Cohorts in Healthy Subjects (Part A) 
Cohort 
Dose 
A1 (sentinel group) 
Single dose of AT-007 oral capsule, dose 0.5 mg/kg (n = 1) 
placebo (n = 1) 
A1 (remainder of 
cohort) 
Single dose of AT-007 oral capsule, dose 0.5 mg/kg (n = 5) 
placebo (n = 1) 
A2  
Single dose of AT-007 oral capsule, dose 5 mg/kg (n = 6) 
placebo (n = 2) 
A3 
Single dose of AT-007 oral capsule, dose 10 mg/kg (n = 6) 
placebo (n = 2) 
A4 
Single dose of AT-007 oral capsule, dose 20 mg/kg (n = 6) 
placebo (n = 2) 
A5 
Single dose of AT-007 oral capsule, dose 40 mg/kg (n=6) 
placebo (n = 2) 
n = number of subjects; SAD = single ascending dose. 
Note: The number of cohorts and total number of subjects may increase if doses above 40 mg/kg are tested in 
additional cohorts. 
3.1.4.2 
Part B: Double-blind MAD, Healthy Subjects 
Four dose levels are planned for the MAD group in Part B (Table 3-3). Subjects will be enrolled 
in 4 sequential cohorts of 6 or 8 subjects each, for a total of 28 subjects. The initial dose level for 
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Part B (5 mg/kg) was based on the results from Part A (Cohorts A1 through A4). Subjects will 
receive study drug (AT-007 or placebo) QD for 7 consecutive days. Progression to and the dose 
level for the next cohort will be dependent upon safety data through Day 8 from the previous 
cohort as well as results from Part A.  
Table 3-3: 
MAD Dose Cohorts in Healthy Subjects (Part B) 
Cohort 
Dose 
B1 
AT-007 oral capsule QD for 7 consecutive days, dose 5 mg/kg (n = 6) 
placebo (n = 2) 
B2  
AT-007 oral capsule QD for 7 consecutive days, dose 10 mg/kg (n = 4) 
placebo (n = 2) 
B3 
AT-007 oral capsule QD for 7 consecutive days, dose 20 mg/kg (n = 6) 
placebo (n = 2) 
B4 
AT-007 oral capsule QD for 7 consecutive days, dose 40 mg/kg (n = 4) 
placebo (n = 2) 
n = number of subjects; MAD = multiple ascending dose; QD = once daily.  
Note: The number of cohorts and total number of subjects may increase if doses above 40 mg/kg are tested in 
additional cohorts. The numbers of subjects in the cohorts are intended to ensure at least 6 subjects on AT-007 at 
each well-tolerated dose level when Cohort C subjects at the same dose level are considered. 
3.1.4.3 
Part C: Open-label MAD, Healthy Subjects 
The first cohort of Part C (i.e., Cohort C1) was conducted concurrently with Cohort B3 but at 
different locations with the same CRU, and the second cohort of Part C (Cohort C2) was 
conducted after Cohort B3. Cohort C1 used the same dose (10 mg/kg) as Cohort B2; Cohort C2 
used the same dose (20 mg/kg) as Cohort B3; and Cohort C3 will use the same dose as and run 
concurrently with Cohort B4 (40 mg/kg) (Table 3-4). Results for prior Part C cohorts will be 
considered before starting the next Part C cohort. Each of the cohorts in Part C will consist of 
only 4 subjects and all subjects will be assigned to open-label AT-007. 
Table 3-4: 
MAD Dose Cohorts in Healthy Subjects with CSF Collection (Part C) 
Cohort 
Dose 
C1 
AT-007 oral capsule QD for 7 consecutive days, dose 10 mg/kg (n = 4) 
C2  
AT-007 oral capsule QD for 7 consecutive days, dose 20 mg/kg (n = 4) 
C3  
AT-007 oral capsule QD for 7 consecutive days, dose 40 mg/kg (n=4) 
n = number of subjects; MAD = multiple ascending dose; QD = once daily.  
 
3.1.4.4 
Part D: SAD and MAD in Subjects with CG 
Three dose levels are planned for the subjects with CG (Table 3-5). Subjects will be enrolled in 3 
sequential cohorts of 6 subjects each for a total of 18 subjects. The initial dose level for Part D 
will be based on the results from Parts A (Cohorts A1 through A4) and Cohorts B1 and B2. 
Subjects will receive study drug (AT-007 or placebo) on Day 1 and remain at the CRU for at 
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least 48 hours after the first dose. Subjects will then have a 5-day washout period (Day 1 
postdose through Day 6 predose). Then, subjects who tolerated the single dose will take the same 
study drug QD for 27 consecutive days (Day 6 through Day 32, inclusive) for the multiple 
dosing portion of Part D. For each individual subject, the Investigator and the Sponsor will 
decide whether the subject can start the multiple dosing portion of Part D. The Investigator must 
consult the Sponsor. Starting the multiple dosing portion requires explicit agreement from the 
Sponsor. In the 27-day multiple dosing portion, subjects will take most of their doses at home 
(fasting conditions recommended). Progression to and the dose level for the next cohort will be 
dependent upon safety data through Day 12 and at least single dose PK and galactitol results 
from the previous cohort as well as additional Part B (and possibly Part C) results.  
Table 3-5: 
SAD and MAD Dose Cohorts in Subjects with Classic Galactosemia (Part D) 
Cohort 
Dose 
D1 
AT-007 oral capsule on Day 1, dose 5 mg/kg (SAD portion), followed by a 5-day-
washout, and AT-007 oral capsule QD for 27 days (MAD portion), dose TBD 
mg/kg (n = 4) 
placebo 
 (n = 2) 
D2  
AT-007 oral capsule on Day 1, dose 20 mg/kg (SAD portion), followed by a 5-day-
washout, and AT-007 oral capsule QD for 27 days (MAD portion), dose TBD 
mg/kg (n = 4) 
placebo  
(n = 2) 
D3 
AT-007 oral capsule on Day 1, dose TBD mg/kg (SAD portion), followed by a 5-
day-washout, and AT-007 oral capsule QD for 27 days (MAD portion), dose TBD 
mg/kg (n = 4) 
placebo  
(n = 2) 
n = number of subjects; MAD = multiple ascending dose; QD = once daily; SAD = single ascending dose; TBD = to 
be determined.  
Note: The number of cohorts and total number of subjects may increase if doses above 40 mg/kg are tested in 
additional cohorts. The overall number of subjects per cohort may be increased up to 8 subjects to address any 
potential lost-to-follow-up among subjects treated with either placebo or AT-007. Subjects treated with study drug 
(placebo or AT-007) in a cohort may be randomized to treatment in another cohort (separate consent required) 
within the same Part (assuming no safety or tolerability issues in the prior cohort) as long as there is a washout 
period ≥5 days between the last dose in a cohort and the first dose in the next cohort. 
3.1.4.5 
Part E: SAD and MAD in Subjects with GALK-deficient Galactosemia 
The starting dose level for subjects with GALK-deficient Galactosemia will be the most 
clinically appropriate dose as determined by the evaluation of safety, tolerability, and PD 
(reduction in galactitol level) in Part D cohorts completed at the time of starting Part E (Table 
3-6). If needed, additional dose levels may be tested in additional cohorts. If applicable, dose 
levels for subsequent cohorts in Part E will be based on safety data through Day 12 and at least 
single dose PK and galactitol results from the previous cohort(s) in Part E and possibly 
additional cohorts in Part D. 
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Subjects will receive study drug (AT-007 or placebo) on Day 1 and remain at the CRU for at 
least 48 hours after the first dose. Subjects will then have a 5-day washout period (Day 1 
postdose through Day 6 predose). Then, subjects who tolerated the single dose will take the same 
study drug QD for 27 consecutive days (Day 6 through Day 32, inclusive) for the multiple 
dosing portion of Part E. For each individual subject, the Investigator and the Sponsor will 
decide whether the subject can start the multiple dosing portion of Part E. The Investigator must 
consult the Sponsor. Starting the multiple dosing portion requires explicit agreement from the 
Sponsor. In the multiple dosing portion, subjects will take most of their doses at home. Subjects 
will return to the site for brief in-clinic stays after the first week of multiple dosing and at the end 
of multiple dosing. Subjects will return for the EOS Visit at 28 days after the last dose. 
Table 3-6: 
Dose Cohort in Subjects with GALK-deficient Galactosemia (Part E) 
Cohort 
Dose 
E1 
AT-007 oral capsule on Day 1, dose TBD mg/kg (SAD portion), followed by a 
5-day-washout, and AT-007 oral capsule QD for 27 days (MAD portion), dose 
TBD mg/kg (n=4) 
placebo (n=2) 
n = number of subjects; MAD = multiple ascending dose; QD = once daily; SAD = single ascending dose; TBD = to 
be determined.  
Note: There may be up to 2 additional cohorts if the decision is made to test more than 1 dose level. Also, the 
number of cohorts and total number of subjects may increase if doses above 40 mg/kg are tested in additional 
cohorts. The overall number of subjects per cohort may be increased up to 8 subjects to address any potential lost-
to-follow-up among subjects treated with either placebo or AT-007. Subjects treated with study drug (placebo or 
AT-007) in a cohort may be randomized to treatment in another cohort (separate consent required) within the same 
Part (assuming no safety or tolerability issues in the prior cohort) as long as there is a washout period ≥5 days 
between the last dose in a cohort and the first dose in the next cohort 
3.1.4.6 
Part D Extension: 90-Day Dosing in Subjects with Classic Galactosemia 
The Part D Extension is open to the following subjects: 
• Subjects who completed Part D may start in the extension at any time after the EOS Visit 
in Part D. 
• Subjects who participated in but discontinued Part D for reasons other than study drug 
related TEAE (and completed an EOS Visit at any time >14 days after the last dose) may 
start in the extension at any time after the EOS Visit in Part D. 
• Subjects who participated in but discontinued Part D for reasons other than study drug 
related TEAE (and who either did not have an EOS Visit or had an EOS Visit before 14 
days after the last dose) may start in the extension at any time beyond 14 days after the 
last dose in Part D. 
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• De novo subjects who did not participate in Part D may participate in the 90-day 
Extension after they undergo all the required screening procedures from Day -40 to Day -
1, including the baseline MRI/MRS (if the necessary consents are obtained for this scan). 
The dose for the first cohort of the Part D Extension (DE1) will be 20 mg/kg/day based on 
acceptable SAD and MAD safety and PK data from Cohort D2 (Table 3-7). After SRC review of 
all SAD and MAD data and Sponsor review of PK and galactitol data for Cohorts D1 through 
D3, a second cohort of the Part D Extension (DE2) may be initiated to evaluate a dose >20 
mg/kg/day if this dose was well tolerated in the SAD and MAD portions of the study in both 
healthy volunteers and subjects with CG.  
A screening visit is required for de novo subjects and subjects whose last visit in Part D was 
>40 days before Day 1 in the Part D Extension. 
Within each cohort of up to 16 subjects, subjects will be randomly assigned in a 3:1 to AT-007 
and placebo. Subjects will receive study drug (AT-007 or placebo) on Day 1 and remain at the 
CRU for at least 24 hours after the first dose. Subjects will receive 1 daily dose of the same study 
drug (AT-007 or placebo) for a total of 90 consecutive days. In the extension, subjects will take 
most of their doses at home. Subjects will have 1 in-clinic stay associated with the first dose, a 
second in-clinic stay with the last dose, and out-patient visits at Months 1 and 2. Subjects will 
return for the EOE Visit at 28 days after the last dose.  
Maximum duration of study participation (Screening through EOE Visit) for an individual 
subject will be approximately 158 days for a de novo subject and approximately 218 days for a 
subject who was screened for Part D, completed Part D, and completed Part D Extension without 
requiring a screening visit for the Part D Extension and without counting any washout period 
between Part D and Part D Extension. 
Table 3-7:  
90-Day Dose Cohort in Subjects with Classic Galactosemia (Part D 
Extension) 
Cohort 
Dose 
DE1 
AT-007 oral capsule on Day 1, dose 20 mg/kg (SAD portion), followed by AT-007 
oral capsule QD for a total of 90 days, dose 20 mg/kg (n=up to 12) 
placebo 
(n=up to 4) 
n = number of subjects; MAD = multiple ascending dose; QD = once daily; SAD = single ascending dose.  
Note: There may be up to 1 additional cohort if the decision is made to test more than 1 dose level. Regardless of 
whether there is 1 or 2 cohorts, the maximum number of subjects is 16. However, the number of cohorts and total 
number of subjects may increase if doses above 40 mg/kg are tested in additional cohorts. The overall number of 
subjects per cohort may be increased to address any potential lost-to-follow-up among subjects treated with either 
placebo or AT-007. 
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3.1.4.7 
Dose Escalation and Dose De-escalation 
The SRC will make recommendations to the Sponsor regarding dose escalation or de-escalation 
for each cohort based on the results from the previous cohort. The Sponsor will act upon this 
recommendation and inform the Investigator(s) and the IRB(s)/IEC(s).  
The SRC will pay particular attention to dose limiting toxicities (DLTs) defined as any AT-007-
related AE or clinically relevant finding on laboratory tests, ECGs, vital signs, or physical 
examinations that, in the opinion of the Investigator and/or the SRC, precludes administering the 
dose to any subject and/or continuing to administer daily doses to the subject who experienced 
the event. For DLTs, as well as fatal serious adverse events (SAEs) and life-threatening SAEs, 
breaking the blind will be considered and initiated (as needed) per SRC discussion and 
agreement.  
Dose-escalation will be stopped and de-escalation initiated if 
• ≥ 2 subjects on AT-007 (B and C cohorts of the same dose level considered together) 
experience a DLT at any time through 24 hours after the last dose of study treatment 
• Any subject on AT-007 has a fatal SAE or life-threatening SAE requiring urgent 
intervention at any time through 24 hours of the last dose of study treatment 
Dose escalation within each part of the study will be continued until the MTD is identified per 
the rules above or the SRC and/or Sponsor decide to stop dose escalation. Dose de-escalation, if 
initiated within any part of the study, will continue until the MTD is identified or the SRC and/or 
Sponsor decide to stop. 
If the events outlined in the above MTD definition do not occur at any dose level in a study part, 
then the MTD will be the highest dose level in that study part.  
If the events outlined in the above MTD definition occur at any given dose level, the Sponsor 
may decide to investigate a dose higher that the previously well-tolerated dose but lower than the 
dose at which one of the events outlined in the above MTD definition occurred. 
3.1.5 
Concomitant Medications 
Subjects must not take any over the counter (OTC) medication (including nutritional or dietary 
supplements, herbal preparations, or vitamins) ≤ 7 days prior to the first dose of study drug until 
the EOS (or end of extension (EOE)) Visit without evaluation and approval by the Investigator. 
For subjects with CG or GALK-deficient Galactosemia, use of medications to treat Galactosemia 
complications will be permitted by approval of the Investigator. 
Subjects must not take any prescription medication, except that allowed per protocol in this 
section, from 14 days prior to the first dose of study drug until the EOS (or EOE) Visit without 
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evaluation and approval by the Investigator. For subjects with CG or GALK-deficient 
Galactosemia, use of medications to treat galactosemia complications will be permitted by 
approval of the Investigator. 
In addition, use or consumption of the following are not permitted: 
• Tobacco- or nicotine-containing products within 6 months prior to the first dose of study 
drug (including negative cotinine test at screening) through the EOS Visit (subjects in 
Parts A, B, and C only) 
• Drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, 
opiates) from a negative drug test at screening through the EOS (or EOE) Visit 
(Exception: Subjects with CG or GALK-deficient Galactosemia may take such drugs or 
drugs that produce positive drug screening results if clinically indicated and on a stable 
dose for ≥ 1 month prior to screening and throughout the study.) 
• Any strong inhibitor/inducer of CYP2C19 and/or CYP3A4 (eg, barbiturates, 
phenothiazines, cimetidine, carbamazepine) within 30 days prior to the first dose of study 
drug through the visit before the EOS (or EOE) Visit 
• Beverages or foods that contain alcohol, high levels of sorbitol, grapefruit, poppy seeds, 
broccoli, Brussels sprouts, pomegranate, star fruit, char-grilled meat, or caffeine/xanthine 
from 48 hours prior to the first dose of study drug through the visit before the EOS (or EOE) 
Visit (allowance for an isolated single incidental consumption may be evaluated and 
approved by the Investigator based on the potential for interaction with the study drug) 
Permitted concomitant medications in this study are the following: 
• Female hormonal contraceptives or hormone replacement therapy (Parts A, B, C, D, E 
and D Extension)  
• Concomitant medications and dietary supplements with stable doses maintained for 
≥ 1 month prior to screening and through the EOS (or EOE) Visit (Part D, E and D 
Extension) 
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3.1.6 
Treatment Compliance 
Treatment compliance is assured during Parts A, B, and C and for in-clinic doses during Part D, 
E and D Extension because subjects will take the study drug in the CRU under supervision by 
the study center staff.  
During Part D, E and D Extension, study drug will be dispensed and collected periodically 
because subjects will be taking most doses at home. Treatment compliance will be determined by 
counting the capsules dispensed and collected at each of these visits and by reviewing subjects’ 
study drug diary cards. 
For Part D, E and D Extension, treatment compliance is defined by the percentage of planned 
dose administered and is calculated as: 
(Actual Number of Dose Taken / Planned Number of Doses) x 100 
3.1.7 
Pharmacokinetic Sampling Schedule 
In Part A, blood samples for plasma AT-007 PK will be collected predose (within 60 min before 
the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours (±5 minutes for all time points) 
after the dose.  
For Part A, Cohort A4 and A5, urine samples for AT-007 PK will be collected predose (spot 
collection within 60 min before the dose) and in 4-hour intervals (0 to 4, > 4 to 8, > 8 to 12, > 12 
to 16, > 16 to 20, and > 20 to 24) through the first 24 hours after the dose followed by 12-hour 
intervals (> 24 to 36, > 36 to 48, > 48 to 60, and > 60 to 72) from 24 hours postdose to 72 hours 
postdose. Allowable windows for urine collection container changes will be ± 30 minutes 
through the first 24 hours and ± 1 hour thereafter. 
In Part B, on Day 1, blood samples for plasma AT-007 PK will be collected predose (within 60 
minutes before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours (± 5 minutes for all time 
points) after the dose. On Day 2, blood samples for plasma AT-007 PK will be collected predose 
(ie, at 24 hours ± 5 minutes after the Day 1 dose and before the Day 2 dose). On Day 7, blood 
samples for plasma AT-007 PK will be collected predose (within 60 minutes before the dose) 
and at 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours (± 5 minutes for all time points) after the dose. Also, 
blood samples for plasma AT-007 PK will be collected at 24, 36, and 48 hours (± 5 minutes for 
all time points) after the Day 7 dose; these collections will be taken on Day 8 and Day 9. 
In Part C, on Day 1, blood samples for plasma AT-007 PK will be collected predose (within 60 
minutes before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours (± 5 minutes for all time 
points) after the dose. On Day 2, blood samples for plasma AT-007 PK will be collected predose 
(ie, at 24 hours ± 5 minutes after the Day 1 dose and before the Day 2 dose). On Day 7, blood 
samples for PK will be collected predose (within 60 minutes before the dose) and at 0.5, 1, 1.5, 
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2, 4, 6, 8, and 12 hours (± 5 minutes for all time points) after the dose. Also, blood samples for 
plasma AT-007 PK will be collected at 24, 36, and 48 hours (± 5 minutes for all time points) 
after the Day 7 dose; these collections will be taken on Day 8 and Day 9. A lumbar puncture will 
be done after the Day 7 dose to collect CSF for analysis of AT-007. For Cohort C1, the timing 
(hours after the dose) of the lumbar puncture will be based on plasma AT-007 PK results from 
Cohorts B1 and B2. For Cohort C2, the timing of the lumbar puncture was based on PK results 
from Cohorts B1, B2, and B3. For Cohort C3, the timing of the lumbar puncture will be based on 
PK results from Cohorts B1, B2, B3, and B4. The intent is to perform the lumbar puncture at the 
time of maximum observed concentration (Tmax) after the Day 7 dose. 
In Part D, for the Day 1 dose, blood samples for plasma AT-007 PK will be collected predose 
(within 60 minutes before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours (± 5 
minutes for all time points) after the dose. On Days 12 and 32, blood samples for plasma AT-007 
PK will be collected predose (within 60 minutes before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, and 
12 hours (± 5 minutes for all time points) after the dose. On Day 13, a blood sample for plasma 
AT-007 PK will be collected predose (ie, at 24 hours ± 5 minutes after the Day 12 dose). On Day 
33, blood samples for plasma AT-007 PK will be collected at 24 and 36 hours (± 5 minutes for 
both time points) after the Day 32 dose. On Day 34, a blood sample for plasma AT-007 PK will 
be collected at 48 hours (± 5 minutes) after the Day 32 dose.  
For Cohort D3 only, urine for PK will be collected predose (spot collection within 60 minutes 
before the Day 1 dose) and in 4-hour intervals (0 to 4, > 4 to 8, > 8 to 12, > 12 to 16, > 16 to 20, 
and > 20 to 24) through the first 24 hours after the Day 1 dose followed by 12-hour intervals (> 
24 to 36, > 36 to 48, > 48 to 60, and > 60 to 72) from 24 to 72 hours after the Day 1 dose. 
Allowable windows for urine collection container changes will be ± 30 minutes through the first 
24 hours and ± 1 hour thereafter. 
In Part E, on Day 1 dose, blood samples for PK will be collected predose (within 60 minutes 
before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours (±5 minutes for all time 
points) after the dose. On Days 12 and 32, blood samples for PK will be collected predose 
(within 60 minutes before the dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours (±5 minutes for all 
time points) after the dose. On Day 13, a blood sample for PK will be collected predose (i.e., at 
24 hours ±5 minutes after the Day 12 dose). On Day 33, blood samples for PK will be collected 
at 24 and 36 hours (±5 minutes for both time points) after the Day 32 dose. On Day 34, a blood 
sample for PK will be collected at 48 hours (±5 minutes) after the Day 32 dose. 
For Part E, Urine for galactitol measurement will be collected over the 24 hours immediately 
before and the 24 hours immediately after the dose on Day 1. Urine for galactitol measurement 
will be collected over the 24 hours immediately after the dose on Days 12 and 32. For each 
collection of urine for galactitol measurement, an aliquot of the total urine collected will be 
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analyzed for creatinine. Also, a spot collection for urine galactitol measurement will be taken at 
screening. 
For Part D Extension, blood samples for PK will be collected on Day 1, a predose (within 60 
minutes before the dose) blood sample for PK will be collected. On Days 30, 60, and 90, blood 
samples for PK will be collected predose (24 hours [± 15 minutes] after the dose taken the day 
before and within 60 minutes before the dose administered on that day) and at 2, 4, 8, and 12 
hours (±5 minutes for all time points) after the dose. 
For Part D Extension, Urine spot collection for galactitol analysis to check the study entry 
criterion based on urine galactitol (applicable only to subjects requiring a screening visit because 
it is assumed that urine galactitol for subjects not requiring the screening visit remain in the study 
eligible range). 
3.1.8 
Evaluation of Biomarkers 
In Part D, E and D Extension, blood samples for the analysis of galactose, galactitol, and 
galactose-1-phosphate and urine samples for the analysis of galactitol will be collected. With the 
exception of the blood samples for biomarkers taken at Screening and Day -1, the time points 
and allowable windows for the blood samples for biomarkers will match those for the blood 
samples for PK. 
3.2 
Evaluation of Treatment Safety 
3.2.1 
Adverse Events 
Adverse events will be monitored from the time the subject signs the informed consent 
throughout the study. AEs will be collected for each subject from the time of informed consent 
through the EOS (or EOE) Visit. The following details will be collected: description of the AE, 
start date and time, stop date and time, action taken with study treatment (dose not changed, dose 
reduced, drug interrupted, drug withdrawn, dose increased, not applicable), outcome 
(recovered/resolved, not recovered/not resolved, recovered/resolved with sequelae, 
recovering/resolving, fatal, unknown), severity (mild, moderate, severe), seriousness (yes, no), 
relationship to study drug (not related, unlikely related, possibly related, probably related). An 
AE is considered “unexpected” if the AE is not listed in the Investigator Brochure or is not listed 
with the observed specificity or severity. 
3.2.2 
Clinical Laboratory Assessments 
A Clinical Laboratory Improvement Amendments certified laboratory will perform the following 
clinical laboratory tests: 
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• Hematology: hemoglobin, hematocrit, total and differential leukocyte count, RBC, and 
platelet count 
• Serum chemistry: albumin, blood urea nitrogen (BUN), creatinine, total bilirubin, 
alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), 
sodium (Na+), potassium (K+), chloride (Cl-), lactate dehydrogenase (LDH), calcium 
(Ca), uric acid, glucose, direct bilirubin (DB), and gamma-glutamyl transferase (GGT) 
• Coagulation: prothrombin time (PT) and international normalized ratio (INR) 
• Serology: blood tests for hepatitis B surface antigen, hepatitis C antibody, and HIV. 
• Urinalysis by an automated or manual urine “dipstick” method: pH, specific gravity, 
protein, glucose, ketones, bilirubin, blood, nitrite, leukocyte esterase, and urobilinogen. If 
protein, occult blood, nitrite, or leukocyte esterase values are out of range, a microscopic 
examination will be performed. 
• Urine drug screen: drugs of abuse (amphetamines, benzodiazepines, barbiturates, 
cannabinoids, cocaine, opiates) 
• Urine cotinine screen (subjects in Parts A, B, and C only) 
• Pregnancy test (all female subjects of childbearing potential) 
• FSH (for female subjects claiming postmenopausal status) 
For Parts D, E and D Extension only, the following tests will be done in addition to the ones 
listed above: 
• GALT (Part D and Part D Extension but only done once for subjects participating in both 
Parts) or GALK (Part E) activity in red blood cells 
• GALT (Part D and Part D Extension but only done once for subjects participating in both 
Parts) or GALK (Part E) gene analysis 
• Aldose Reductase activity  (only done once for subjects participating in both Parts D and 
D Extension) 
Fasted samples for hematology, coagulation, chemistry, and urinalysis assessments will be 
collected at the following time points: 
• Part A: Screening, Day -1, Day 3, EOS  
• Part B: Screening, Day -1, Day 6, EOS 
• Part C: Screening, Day -1, Day 6, EOS 
• Part D: Screening, Days -1, 6, 12, 20, 32, EOS 
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• Part E: Screening, Days -1, 6, 12, 20, 32, EOS 
• Part D Extension: Screening, Days -1, 30, 60, 90, EOE 
3.2.3 
Vital Signs 
Vital signs (blood pressure, pulse rate, respiration rate, and temperature) will be measured as 
follows: 
• Part A: Screening, Day -1 check-in, predose (within 60 min before the dose) on Day 1, at 
4 hours (±10 minutes) after the dose on Day 1, once daily on Days 2 and 3, and EOS  
• Part B: Screening, check-in on Days -1 and 6, predose (within 60 min before the dose) on 
Days 1 and 7, at 4 hours (±10 minutes) after the dose on Days 1 and 7, once daily on 
Days 2, 8, and 9, and EOS  
• Part C: Screening, check-in on Days -1 and 6, predose (within 60 min before the dose) on 
Days 1 and 7, at 4 hours (±10 minutes) after the dose on Days 1 and 7, once daily on 
Days 2, 8, and 9, and EOS 
• Part D: Screening, every check-in, every check-out, predose (within 60 min before the 
dose) and 4 hours (±10 minutes) after the dose on Days 1, 6, 12, 20, and 32, once daily on 
all other in-clinic days, and EOS 
• Part E: Screening, every check-in, every check-out, predose (within 60 min before the 
dose) and 4 hours (±10 minutes) after the dose on Days 1, 6, 12, 20, and 32, once daily on 
all other in-clinic days, and EOS 
• Part D Extension: Screening (if applicable), every check-in, every check-out, predose 
(within 60 min before the dose) and 4 hours (±10 minutes) after the dose on Days 1, 30, 
60, and 90, once daily on all other visits, and at the EOE visit.  
Additional vital signs measurements may be taken as deemed medically necessary by the 
Investigator/designee. For purposes of qualifying any given subject for study participation, out of 
range vital signs may be repeated once. 
All vital signs measurements will be taken with the subject in a seated position and after the 
subject has been resting in that seated position for at least 5 minutes. Any time during the study 
after the first dose of study drug, abnormal vital sign measurements considered to be clinically 
significant by the Investigator/designee will be reported as AEs. 
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3.2.4 
Electrocardiograms 
The ECGs will be performed as follows: 
• Part A: Screening, Day -1 check-in, predose (within 60 min before the dose) on Day 1, at 
2 hours (±10 minutes) after the dose on Day 1, on Day 3, and EOS  
• Part B: Screening, Day -1 check-in, predose (within 60 min before the dose) on Days 1 
and 7, at 2 hours (±10 minutes) after the dose on Days 1 and 7, and EOS  
• Part C: Screening, Day -1 check-in, predose (within 60 min before the dose) on Days 1 
and 7, at 2 hours (±10 minutes) after the dose on Days 1 and 7, and EOS 
• Part D: Screening, Day -1 check-in, predose (within 60 min before the dose) and 2 hours 
(±10 minutes) after the dose on Days 1, 6, 12, 20, and 32, and EOS 
• Part E: Screening, Day -1 check-in, predose (within 60 min before the dose) and 2 hours 
(±10 minutes) after the dose on Days 1, 6, 12, 20, and 32, and EOS 
• Part D Extension: Screening, Day -1 check-in, predose (within 60 min before the dose) 
and 2 hours (±10 minutes) after the dose on Days 1, 30, 60, and 90, and EOE 
All ECGs will be done with the subject in a supine position and after the subject has been resting 
in that supine position for at least 5 minutes. 
3.2.5 
Physical Examinations 
Physical examinations will be performed as follows: 
• Part A: Screening; Days -1 and 3; and EOS  
• Part B: Screening; Days -1, 6, and 9; and EOS  
• Part C: Screening; Days -1, 6, and 9; and EOS 
• Part D: Screening; Days -1, 6, 12, 20, 32, and 34; and EOS 
• Part E: Screening; Days -1, 6, 12, 20, 32, and 34; and EOS 
• Part D Extension: Screening; Days -1, 30, 60 and 90; and EOE 
Height will be measured at screening. Weight will be measured as part of all physical 
examinations. Any time during the study after the first dose of study drug, abnormal findings 
considered to be clinically significant by the Investigator/designee will be reported as AEs.  
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3.2.6 
Other Safety Assessments 
In Parts D and E, brain MRI/MRS will be performed during the Screening Period and toward the 
end of the MAD treatment (i.e., either on Day 30, Day 31, or Day 32). MRI/MRS will only be 
performed in a subset of subjects who specifically consent to the brain imaging.  
In Part D Extension, brain MRI/MRS will be performed during the Screening Period (unless the 
subject previously participated in Part D and had a brain MRI/MRS performed during the 
Screening Period for Part D) and toward the end of the treatment period (i.e., either on Day 88, 
Day 89, or Day 90).  MRI/MRS will only be performed in subjects who specifically consent to 
the brain imaging. 
3.2.7 
Protocol Deviation Reporting 
Procedural deviations found by the clinical research associate (CRA) during monitoring visits 
and data deviations captured on the electronic case report form (eCRF) and found through 
programming and examining the database will be listed by subject. 
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4 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSIS 
There are a few changes in the study conduct or analysis plans relative to the study protocol: 
• The objective “To evaluate the effect of single and multiple doses of orally administered 
AT-007 on the levels of galactose and its other metabolites in adult subjects with CG or 
GALK-deficient Galactosemia“ is a secondary objective according to the study protocol, 
but it should be an exploratory objective only.   
• The secondary endpoint “Galactose, galactitol, and other galactose metabolites in the 
blood of subjects with CG and subjects with GALK-deficient Galactosemia” was 
replaced by “Galactitol in the blood of subjects with CG and subjects with GALK-
deficient Galactosemia” and the exploratory endpoint “Galactose and galactose 
metabolites in the blood of subjects with CG and subjects with GALK-deficient 
Galactosemia” was added.  
• Additional subgroup analysis performed for Part D blood and urine Galactitol will be 
performed if data permit. 
• Urine galactitol concentrations for each collection interval will also be presented 
normalized to urine creatinine. 
• The DBL will be carried out after the completion of Part D and CSR will be written for 
Part A to D. This will lead to unblinding of Part A and Part B subjects to the study team. 
Part D- Extension will be carried out as CSR addendum. 
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5 
QUALITY CONTROL AND QUALITY ASSURANCE METHODS FOR DATA 
ANALYSIS 
Case report forms will be monitored and collected by ICON. All monitored eCRFs will be sent 
to the Data Management group at ICON and processed according to the ICON Study Specific 
Procedure SSP DM-48480001.01 Data Management Plan (DMP). The DMP describes eCRF 
data processing, edit checks, data query management, medical dictionary coding, SAE 
reconciliation, data transfers, and data quality review through database lock or any necessary 
reopening of the database. After database lock, the data will be retrieved from the database using 
SAS® version 9.4 or higher. 
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6 
PHARMACOKINETIC ASSESSMENTS 
6.1 
Pharmacokinetic Assessments 
6.1.1 
Pharmacokinetic Analysis 
Pharmacokinetic parameters will be calculated from the plasma concentration-time data using 
noncompartmental techniques (Phoenix WinNonlin, Build 8.0.0.3176 or higher, Certara L.P. 
(Pharsight), St. Louis, MO) and actual sampling times. PK parameters will also be determined 
using the urine concentration data collected over 48 hours after dosing (Cohort A4 and A5). 
For subjects in Part C, a Day 7 lumbar puncture will be done to collect CSF for AT-007 
measurement using a qualified assay. 
The PK parameters in Table 6-1will be determined for the SAD parts of the study (i.e. Part A the 
single dose period of Part D and E). 
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Table 6-1: 
Pharmacokinetic Parameters of AT-007 After a Single Dose in Healthy Subjects 
(Part A) and Subjects with Classic Galactosemia (Single Ascending Dose Period 
of Part D and E) 
Parameter 
Definition 
Cmax 
Maximum concentration, determined directly from individual concentration time data 
Tmax 
Time of the maximum concentration 
λz 
The observed terminal rate constant; estimated by linear regression through at least 3 data 
points in the terminal phase of the log concentration-time profile 
T1/2 
The observed terminal half-life, calculated as: 
z
T

)
2
ln(
2
/
1
=
 
AUClast 
Area under the concentration-time curve from time-zero to the time of the last quantifiable 
concentration; calculated using the linear trapezoidal rule 
AUCinf 
Area under the concentration-time curve from time-zero extrapolated to infinity; calculated 
as: 
z
last
last
C
AUC
AUC

+
=
inf
 
AUCExtrap (%) 
The percentage of AUCinf based on extrapolation 
Clast 
The last quantifiable concentration determined directly from individual concentration-time 
data 
Tlast 
Time of the last quantifiable concentration 
CL/F 
Clearance after extravascular administration, calculated as: 
CL/F = Dose/AUCinf 
Vz/F 
Volume of distribution in the terminal phase, calculated as: 
Vz/F = (CL/F)/λz 
The PK parameters in Table 6-2will be determined for the MAD parts of the study (ie, Parts B, 
C, and multiple dosing period in Parts D and E, and Part D Extension). 
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Table 6-2: 
Pharmacokinetic Parameters of AT-007 During Multiple Dosing in Healthy 
Subjects (Parts B and C) and Subjects with Galactosemia (Multiple Ascending 
Dose Period of Parts D and E and Part D Extension) 
PK Parameter 
Definition 
Cmax 
Maximum concentration, determined directly from individual concentration time data (Day 1 
and Day of Last Dose) 
Tmax 
Time of the maximum concentration (Day 1 and Day of Last Dose) 
λz 
The observed terminal rate constant; estimated by linear regression through at least 3 data 
points in the terminal phase of the log concentration-time profile (Day of Last Dose only) 
T1/2 
The observed terminal half-life, calculated as: 
z
T

)
2
ln(
2
/
1
=
 (Day of Last Dose only)  
AUCtau 
Area under the concentration-time curve during the 24-hour dosing interval; calculated using 
the linear trapezoidal rule (Day 1 and Day of Last Dose) 
Note: If quantifiable data are not observed through 24 h postdose, AUCtau will be estimated 
using extrapolation (from the time of the last reported concentration to 24 h) and AUClast will 
also be reported. 
AUClast 
Area under the concentration-time curve from time-zero to the time of the last quantifiable 
concentration; calculated using the linear trapezoidal rule (Day of Last Dose; Day 1 if 
quantifiable data are not observed through 24 h postdose) 
AUCinf 
Area under the concentration-time curve from time-zero extrapolated to infinity; calculated 
as: 
z
last
last
C
AUC
AUC

+
=
inf
 (Day of Last Dose only)  
AUCExtrap (%) 
The percentage of AUCinf based on extrapolation (Day of Last Dose only) 
Clast 
The last quantifiable concentration determined directly from individual concentration-time 
data (Day 1 and Day of Last Dose) 
Tlast 
Time of the last quantifiable concentration (Day 1 and Day of Last Dose) 
CL/F 
Clearance after extravascular administration, calculated as: 
CL/F = Dose/AUCtau (Day X),  
where Day X = Day of Last Dose and Dose is the actual dose administered (mg/kg x kg). 
(Day of Last Dose only) 
Note: CL/F/kg may also be reported  
Vz/F 
Volume of distribution in the terminal phase, calculated as: 
Vz/F = (CL/F)/λz (Day of Last Dose only) 
Note: Vz/F/kg may also be reported 
Rac 
The accumulation ratio during multiple dose administration, based on Cmax and AUCtau; 
calculated as:  
Rac (AUCtau) = AUCtau (Day X) / AUCtau (Day 1) 
Rac (Cmax) = Cmax (Day X) / AUCtau (Day 1) 
Note: Rac will be tabulated with the pharmacokinetic parameters on Day X. 
Note: Day X = Day of Last Dose 
Note: Day of Last Dose is Day 7 in Parts B and C, Day 32 in in the MAD portion of Part D and E, and Day 90 in 
Part D Extension  
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Urine concentration data from Part A4, A5 and Part D3 will be used to determine the following 
parameters: 
Ae  
Amount excreted into urine, calculated over 72 hours 
Fe%  
Fraction of drug excreted in urine over 72 hours, calculated as Ae/dose X 
100% 
Only data points that describe the terminal elimination log-linear decline will be used in the 
regression equation for calculation of terminal elimination phase rate constant; Cmax and any data 
point in the distribution phase are not included in the calculation. A minimum of 3 points will be 
used for determination of the terminal elimination phase rate constant. A general rule of adjusted 
R2 >0.80 will be considered as acceptable for calculation of the terminal elimination phase rate 
constant. If the adjusted R2 falls below 0.80, then the terminal elimination phase rate constant 
will be reported as not determined (ND) and that subject’s z, t1/2, AUCinf, CL/F, and Vz/F will 
be reported as ND in the appropriate listings. If the extrapolated AUCinf is more than 20%, then 
AUCinf, CL/F and Vz/F will be listed but excluded from descriptive summaries and statistical 
analysis. 
6.1.2 
Treatment of Outliers 
Individual concentration-time points, if considered anomalous, may be excluded from the 
analysis at the discretion of the pharmacokineticist following a review of the available 
documentation. Any such exclusion will be discussed with the sponsor and clearly outlined in the 
study report. 
Entire individual treatment profiles for a subject may be excluded following review of the 
available documentation and discussion with the sponsor. However, results of analysis with and 
without the excluded profiles may be presented in the study report. Any such exclusion will be 
clearly listed in the study report along with justification for exclusion. 
Any anomalous concentration values observed at predose will be identified and discussed in the 
CSR. Pharmacokinetic parameters will be computed if the predose concentration value is not 
greater than 5% of Cmax for a given subject. If the predose concentration value is greater than 5% 
of Cmax concentration on Day 1, then the PK parameter data for the given subject will be listed 
but excluded from the PK summaries and statistical analysis. Subjects who experience emesis 
during the course of the study will be excluded from the PK summaries and statistical analysis if 
vomiting occurs at or before 2 times median Tmax. 
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6.1.3 
Non-Quantifiable Concentrations 
All concentration values reported as no results (not collected or not determined) values will be 
treated as missing. For the calculation of concentration summaries, all concentrations below the 
quantifiable limit (BLQ) will be treated as 0. For the purpose of calculating PK parameters and 
plotting mean and individual concentration-time profiles, concentrations below the lower limit of 
quantitation (BLQ) will be treated as zero prior to the the first quantifiable concentration; 
subsequent values BLQ concentrations will be treated as “missing.”  
 
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7 
STATISTICAL METHODS 
7.1 
General 
The statistical analysis will be conducted following the principles specified in the International 
Council for Harmonization (ICH), formerly the International Conference of Harmonization, 
Topic E9 Statistical Principles for Clinical Trials (CPMP/ICH/363/96). 
All statistical tabulations and analyses will be done using SAS®, Version 9.4 or higher. 
Unless otherwise noted, for continuous outcomes, descriptive statistics will include the number 
of subjects, mean, 95% confidence interval (CI) for the mean, standard deviation (SD), median, 
minimum (Min), maximum (Max), 25th percentile, and 75th percentile. For categorical outcomes, 
the number and percentage of subjects will be presented. Descriptive statistics will generally be 
presented by AT-007 group. For summaries of continuous AT-007 PK concentration and 
parameter data, the coefficient of variation will also be presented.  
In the data listings, study day relative to first dose of study drug may be presented. Study day 
relative to first dose will be calculated as: event date - first dose date (+ 1 if event day ≥ first 
dose date). 
For analyses of change from baseline, baseline will generally be defined as the predose 
assessment on Day 1 or Day -1, as scheduled. If this value is unavailable, the last non-missing 
value prior to dosing will be used.  
All data from the CRFs, as well as any derived variables, will be presented in data listings.  
For safety summaries, the unscheduled and repeat assessments will not be summarized; however, 
all results will be included in the data listing. 
Unless otherwise noted, the analyses will be done by Parts and actual treatment/dose received.  
Three sets of outputs will be created: One set for Part A, B, C, and D, one set for Part D 
Extension and one set for Part E(as detailed below). In creating tables in 3 sets, parts already 
completed can be analyzed earlier than the whole study has been completed.  
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Study Part 
Study Population 
Design 
Table 
Part A 
Healthy Adult Subjects 
SAD 
Parts A, B, C, and D  will be 
summarized under 1st  set 
Part B 
Healthy Adult Subjects 
MAD (QD for 7 days) 
Part C 
Healthy Adult Subjects 
MAD (QD for 7 days) 
Part D 
Adult Subjects with CG 
SAD, 5-day washout, MAD 
(QD for 27 days) 
Part D 
Extension 
Adult Subjects with CG 
MAD (QD for 90 Days) 
Part D Extension will be 
summarized under 2nd set 
Part E 
Adult Subjects with GALK-
deficient Galactosemia 
SAD, 5-day washout, MAD 
(QD for 27 days) 
Part E will be summarized 
under 3rd set 
 
7.2 
Handling of Dropouts or Missing Data  
Missing observations will be treated as missing at random, and Missing data will not be imputed. 
7.3 
Multicenter Studies 
For Part A, B and C, this is a monocenter study. For Part D, E and D Extension, this is a 
multicenter study. For the purpose of PK and safety analysis data across sites will be pooled 
together and presented per dose group.  
7.4 
Examination of Subgroups 
For Parts D, E and D Extension, blood galactitol changes will be analyzed based on below 
subgroup categories if data permit: 
• Gender:  Male / Female 
• Age: < 21 years / >= 21 years and < 30 years / >= 30 years 
• BMI: <22 kg/m^2 / 22-25 kg/m^2 / >25 kg/m^2 
• Enzyme activity: <0.1%, 0.1-0.4%, >0.4% 
Additionally forest plot will be displayed for Part D and E at Day 32 and for Part D extension at 
Day 90/EOT for blood galactitol results. 
7.5 
Analysis Populations 
Two analysis populations will be defined: 
• Screened Population (SP): The screened population will consist of all subjects who are 
screened independent if they were eligible or not. 
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• Randomized Population: The randomized population will consist of all subjects who are 
randomized to any cohort. 
• Safety Population: The safety population will consist of all subjects who are randomized 
and receive at least 1 dose of study drug. All analyses will be performed according to 
treatment received. This population will be used for all analyses of safety data and 
biomarker data. 
• Pharmacokinetic Population: The PK population will consist of all subjects who receive 
at least 1 dose of AT-007 and have sufficient concentration-time data to estimate at least 
one of the planned PK parameters, as determined by the study Pharmacokineticist. This 
population will be used for all analyses of PK. 
For Parts D and E, the safety and PK population may be defined separately for the SAD and 
MAD periods. 
7.6 
Subject Accountability 
Summaries of analysis populations and subject disposition will be presented by parts and will 
contain the following information: 
• Number and percentage of subjects screened and screened failure  
• Number and percentage of subjects enrolled  
• Number and percentage of subjects randomized 
• Number and percent of subjects who are dosed  
• Number and percent of subjects who completed the study 
• Number and percent of subjects who discontinued from study early and reason for early 
discontinuation 
• Number and percent of subjects in each population 
Subject disposition will be presented in listings using screened population. 
7.7 
Drug Exposure and Compliance 
A data listing, by subject, containing study drug dosing and dosing errors, if any, will be 
provided.  
For Parts D, E and D Extension, summary of compliance, including compliance categories of 
less than 80%, between 80% and 120%, and greater than 120%, will be reported by treatment 
group and study parts based on Safety Population. Compliance data will also be listed by study 
participants for each Part and Cohort. 
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7.8 
Protocol Deviation Reporting 
Important protocol deviations (IPD) will be identified and classified by the deviation types in the 
IPD document. 
A listing of all IPDs identified will be presented for all subjects based on the safety population 
(SP) and will include the deviation type and description.  
7.9 
Subject Demographics and Baseline Characteristics 
Demographic and baseline characteristics (including age, sex, race, ethnicity, weight, height, and 
body mass index) will be summarized using descriptive statistics by parts and cohorts based on 
safety population.  Also disease characteristics will be summarized i.e. Blood Galactitol, Urine 
Galactitol, Blood Galactose, Blood GAL-1P, Blood Galactonate and Brain galactitol (MRS) for 
Part D, D extension and Part E.  No formal statistical analyses will be performed. 
The medical history of all subjects as well as the neurological history of subjects with CG and 
subjects with GALK-deficient Galactosemia will be coded by system organ class (SOC) and 
preferred term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) version 
22.0 or higher. The number and percentage of subjects with abnormal findings in each SOC and 
each PT will be summarized by parts and cohorts based on safety population. 
7.10 
Analysis of Pharmacokinetic Data 
Plasma and urine PK parameters of AT-007 (including metabolites if determined) will be 
summarized by dose level and part using descriptive statistics. CSF concentration of AT-007 for 
cohort C1, C2 and C3 will be summarized by Cohort.  
The PK Population will be used for all listings, concentration summaries, PK summaries and 
statistical analysis. The individual sampling and subject concentration-time for plasma and CSF 
concentrations will be listed and displayed graphically (plasma only) on linear and semi-log 
scales. The plasma and CSF drug concentrations will be summarized descriptively by nominal 
time point, Part and Cohort in tabular and graphical (plasma only) formats (linear and semi-log 
scales). The amount of AT-007 in urine will be listed by subject and summarized by nominal 
collection interval, Part and Cohort. Summary statistics will include: n, arithmetic mean, 
standard deviation (SD), coefficient of variation (CV%), median, minimum, maximum, and 
geometric mean (GM).  
Pharmacokinetic parameters for AT-007 will be listed and summarized descriptively by Part, 
Cohort and Day, including n, arithmetic mean, SD, minimum, median, maximum, CV(%),GM, 
geometric SD, geometric CV%; geometric CV% calculated as the square root of the 
exponentiated SD of the natural log transformed data (SQRT(exp(sln2)-1)), where appropriate. 
For tmax, only n, minimum, median, and maximum will be reported.  
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The dose proportionality of the primary PK parameters, AUClast, AUCinf and Cmax after single 
dose (Part A, Part D and E, single dose portion) and  AUCtau, and Cmax for single and multiple 
doses, over the administered dose range will be investigated using the following power model,  
log(PK parameter) = a + b * log(dose), where a is the intercept and b is the slope. 
Dose proportionality will be assessed for each part of the study separately. Furthermore, pooling 
of data across all parts at same dose level may be used to access overall dose proportionality for 
the entire range of the administered doses. However, pooling will be based on either the Day 1 
dose or following multiple doses. 
Each log-transformed PK parameter will be fit with a power model with a fixed effect term for 
log-transformed dose.  For each PK parameter, the slope and associated 90% CI will be 
presented.  A minimum of 3 values per dose cohort must be available for a given parameter to 
estimate dose proportionality with the power model. 
The following is the example SAS code can be implemented: 
PROC MIXED DATA=PKPARM; 
 
BY PARAMCD; 
 
MODEL LOGPK= LOGDOSE / SOLUTION CL DDFM=KR; 
     ESTIMATE "SLOPE" LOGDOSE 1 / ALPHA = 0.1 CL; 
 
ESTIMATE "INTERCEPT" INTERCEPT 1 / ALPHA = 0.1 CL; 
 
ODS OUTPUT SOLUTIONF =SOLNF; 
 
ODS OUTPUT ESTIMATES =ESTIMATE; 
RUN;  
7.11 
Analysis of Biomarker Data 
For Part D and E: 
• Plasma Galactitol, the analysis should evaluate maximum galactitol reduction (absolute 
change and percent change) defined as the lowest galactitol value on any of the following 
days of treatment (Day 1, Day 12,  Day 32) vs. Galactitol level at baseline (calculated as 
a mean of 2 pre-dose measurements, such as Day -1 and Time-0 on Day 1 of dosing) 
• Plasma Galactose, the analysis should evaluate the pre-dose galactose level on Day 12 
and Day 32 vs. Galactose level at baseline (evaluated as a mean 2 pre-dose measurement, 
such as Day -1 and Time-0 on Day 1 of dosing) 
• Whole blood Gal-1P the analysis should evaluate the pre-dose Gal-1P on Day 12 and Day 
32 vs. Gal-1P level at baseline (evaluated as a mean 2 pre-dose measurement, such as 
Day -1 and Time-0 on Day 1 of dosing) 
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In addition, plasma galactitol changes will be analyzed based on below subgroup categories if 
data permit: 
• Gender:  Male / Female 
• Age: < 21 years / >= 21 years and < 30 years / >= 30 years 
• BMI: <22 kg/m^2 / 22-25 kg/m^2 / >25 kg/m^2 
• Enzyme activity: <0.1%, 0.1-0.4%, >0.4% 
Urine galactitol levels will be provided as tabulated values and they will not be subjected to a 
formal analysis. 
For genetic analysis, allele specific mutations will be reported as tabulated information   
7.12 
Analysis of Safety Data 
7.12.1 
General 
The evaluation of safety will be based on the occurrence of treatment-emergent adverse events 
(TEAEs); discontinuations from study drug and/or the study because of AEs; clinical laboratory 
test results, physical examination findings, vital sign evaluations, and 12-lead ECGs results. All 
safety endpoints will be summarized descriptively. No statistical inference will be applied to the 
safety endpoints. Descriptive statistics will be calculated for quantitative safety data and 
frequency counts will be compiled for classification of qualitative safety data. 
Safety measures including the baseline data will be summarized descriptively within each part 
(Parts A, B, C, D, E and D Extension) of the study by each cohort (dose level of AT-007 and 
placebo), pooled AT-007 group, and pooled placebo group. 
For analyses of change from baseline, baseline will generally be defined as the predose 
assessment on Day 1 or Day -1, as scheduled. If this value is unavailable, the last nonmissing 
value prior to dosing will be used. Otherwise, missing observations will be treated as missing at 
random, and no data imputation will be performed. All data from the eCRFs, as well as any 
derived variables, will be presented in data listings. 
7.12.2 
Adverse Events 
All AEs will be coded to system organ class (SOC) and preferred term (PT) using MedDRA, 
Version 22.0 or later, and presented by subject data listings. 
A treatment-emergent AE (TEAE) is defined as an AE that is not present prior to cohort with 
investigational product, but appeared following cohort or was present at cohort initiation but 
worsened during cohort. An AE that was present at cohort initiation but resolved and then 
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reappeared while the subject was on cohort is a TEAE (regardless of the intensity of the AE 
when the cohort was initiated). Programmatically, an AE will be classified as a TEAE if the start 
date and time occurs on or after the start date and time of first investigational product dosing. 
The TEAE will be assigned to treatment based on the start date/time of occurrence. 
The overall incidence of TEAEs (number and percentage of subjects) as well as the number of 
events will be summarized by cohort, severity grade, SAEs, causally related TEAE and SAEs, 
TEAEs leading to study or treatment discontinuation, life-threatening SAEs, and SAEs resulting 
in death. 
The TEAEs will be summarized and tabulated at both the subject (number [%] of subjects) and 
event (number of events) level: 
• By cohort, SOC, and PT 
• By cohort, SOC, PT, and maximum reported severity  
• By cohort, SOC, PT, and closest relationship to study drug 
For the incidence at the subject level by SOC and PT, if a subject experiences more than 1 event 
within the same SOC and PT, only 1 occurrence will be included in the incidence. 
For the incidence at the subject level by SOC, PT, and severity, if a subject experiences more 
than 1 event within the same SOC and PT, only the highest severity grade will be included in the 
incidence. 
For the incidence at the subject level by SOC, PT and relationship to study drug; if a subject 
experiences more than 1 event within the same SOC and PT, only the most closely related 
occurrence will be included in the incidence. 
Any SAEs, AEs with outcome of deaths, or AEs resulting in discontinuation of study or cohort 
will be presented. 
7.12.3 
Clinical Laboratory Assessments 
Observed and change from baseline of continuous clinical laboratory values (serum chemistry, 
hematology, coagulation, and urinalysis) for each parameter will be summarized by Part and 
cohort at each scheduled nominal time point. The number and percentage of subjects with shift 
changes from baseline based on the laboratory normal ranges will be tabulated. Laboratory data 
will be listed by subject at each time point. Clinical laboratory values that are out of normal 
ranges will be presented in a separate listing. Urinalysis laboratory tests will be presented in data 
listings only. 
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7.12.4 
Vital Signs 
Vital signs data will be listed by subject at each nominal time point. Observed and change from 
baseline vital signs values will be summarized by part and cohort at each nominal time point for 
SP. 
7.12.5 
Electrocardiograms 
Observed values and change form baseline of 12-lead ECG parameters (HR, RR, PR, QRS, QT, 
and QTcF intervals) will be summarized descriptively by Part and cohort at each scheduled time 
point collected for SP. Individual ECG data will be listed for SP. 
7.12.6 
Physical Examinations 
Physical examination findings will be presented in a subject listing for SP. 
7.12.7 
Prior and Concomitant Medications 
Prior and concomitant medications will be summarized separately by the World Health 
Organization Drug Dictionary (Version March 2016 or later) and classified according to ATC 
codes levels 2 (therapeutic sublevel) and preferred name . Prior and concomitant medication data 
will be listed for each part, each cohort/dose using safety population. 
7.13 
Sample Size 
No formal sample size calculation is required. The approximate sample size (up to 40 healthy 
subjects in Part A, up to 40 healthy subjects in Parts B and C combined, up to 34 subjects with 
CG in Part D and Part D Extension combined if no subject participates in both, and up to 
18 subjects with GALK-deficient Galactosemia in Part E) is not based on statistical 
considerations. The number of subjects is typical for Phase 1 studies of this type and is adequate 
to meet study objectives. 
The number of cohorts and/or total number of subjects may increase if the PK data reveal an 
insufficient exposure at 40 mg/kg. In Parts D and E, the overall number of subjects per cohort 
may be increased up to 8 subjects to address any potential lost-to-follow-up among subjects 
treated with either placebo or AT-007. In Parts D and E, subjects treated with study drug 
(placebo or AT-007) in a cohort may be randomized to treatment in another cohort (separate 
consent required) within the same Part (assuming subject had no safety or tolerability issues in 
the prior cohort) as long as there is a washout period ≥5 days between the last dose in a cohort 
and the first dose in the next cohort. Subject to certain timing considerations, Part D subjects 
may also participate in Part D Extension (separate consent required). 
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7.14 
Interim Analysis 
No interim analysis will be performed.  
But within each part (A, B, C, D, E and D Extension) of the study, the Safety Review Committee 
will review safety (including AE, laboratory, physical examination, vital signs, and ECG data) 
through Day 3 in Part A, Day 8 in Parts B and C, and Day 12 in Parts D and E, respectively for 
each cohort and provide a recommendation to proceed or not to proceed to the next cohort as 
well as the dose level for AT-007. The AT-007 dose level may be increased, decreased, or repeated 
from one cohort to the next. 
 
 
 
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7.15 
General Conventions for Tables, Listings and Figures  
Tables and listings will be presented in landscape mode with minimum of 3/4” bound edge 
margin and 3/8” other margins on 8.5” x 11” paper. 
Times new roman font size of no less than 8 point will be used for tables and listings. 
A source line will be included on the bottom of each page of all tables and listings. It will contain 
the SAS code program name and the run date and time. 
Each variable is recorded to a specific number of decimal places. If the raw data is presented 
with varying precision, then the least precise value will be considered as the data precision. 
For summary tables, unless otherwise specified, the number of decimal places provided in the 
SAS output will be based on the accuracy of the least accurate value in the raw data as follows: 
n 
integer 
Arithmetic mean 
1 decimal place more than the least accurate number in the raw data 
SD 
2 decimal place more than the least accurate number in the raw data 
CV(%) 
2 decimal places 
Geometric mean 
1 decimal place more than the least accurate number in the raw data 
Median 
1 decimal place more than the least accurate number in the raw data 
Percentiles 
1 decimal place more than the least accurate number in the raw data 
Minimum 
same number of decimal places as raw data 
Maximum 
same number of decimal places as raw data 
Confidence interval  
same number of decimals as the associated statistic 
Geometric mean ratio 2 decimal places 
 
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8 
TABLES, FIGURES, AND LISTINGS 
Table/Figure 
Number 
Table/Figure Name 
Section 14.1 
Demographic and Subject Characteristics Data Summaries 
Table 14.1.1a 
Summary of Subject Disposition – Part A (All Screened Population) 
Table 14.1.1b 
Summary of Subject Disposition – Part B and Part C (All Screened 
Population) 
Table 14.1.1c 
Summary of Subject Disposition – Part B and Part C cohorts 
combined (All Screened Population) 
Table 14.1.1d 
Summary of Subject Disposition – Part D (All Screened Population) 
Table 14.1.1de 
Summary of Subject Disposition – Part D Extension (All Screened 
Population) 
Table 14.1.1e 
Summary of Subject Disposition – Part E (All Screened Population) 
Table 14.1.2a 
Summary of Analysis Populations – Part A (Randomized Population) 
Table 14.1.2b 
Summary of Analysis Populations – Part B and Part C (Randomized 
Population) 
Table 14.1.2c 
Summary of Analysis Populations – Part B and Part C cohorts 
combined (Randomized Population) 
Table 14.1.2d 
Summary of Analysis Populations – Part D (Randomized Population) 
Table 14.1.2de 
Summary of Analysis Populations – Part D Extension (Randomized 
Population) 
Table 14.1.2e 
Summary of Analysis Populations – Part E (Randomized Population) 
Table 14.1.3a 
Summary of Demographic and Baseline Characteristics – Part A 
(Safety Population) 
Table 14.1.3b 
Summary of Demographic and Baseline Characteristics – Part B and 
Part C (Safety Population) 
Table 14.1.3c 
Summary of Demographic and Baseline Characteristics – Part B and 
Part C combined (Safety Population) 
Table 14.1.3d 
Summary of Demographic and Baseline Characteristics – Part D 
(Safety Population) 
Table 14.1.3de 
Summary of Demographic and Baseline Characteristics – Part D 
Extension (Safety Population) 
Table 14.1.3e 
Summary of Demographic and Baseline Characteristics – Part E 
(Safety Population) 
Table 14.1.4a 
Medical and Surgical History – Part A (Safety Population) 
Table 14.1.4b 
Medical and Surgical History – Part B and Part C (Safety Population) 
Table 14.1.4c 
Medical and Surgical History – Part B and Part C cohorts combined 
(Safety Population) 
Table 14.1.4d 
Medical and Surgical History – Part D (Safety Population) 
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Table 14.1.4de 
Medical and Surgical History – Part D Extension (Safety Population) 
Table 14.1.4e 
Medical and Surgical History – Part E (Safety Population) 
Table 14.1.5d 
Summary of Treatment Compliance – Part D (Safety Population) 
Table 14.1.5de 
Summary of Treatment Compliance – Part D Extension (Safety 
Population) 
Table 14.1.5e 
Summary of Treatment Compliance – Part E (Safety Population) 
Table 14.1.6a 
Summary of Prior Medication by ATC Classification and preferred 
term – Part A (Safety Population) 
Table 14.1.6b 
Summary of Prior Medication by ATC Classification and preferred 
term – Part B and Part C (Safety Population) 
Table 14.1.6c 
Summary of Prior Medication by ATC Classification and preferred 
term – Part B and Part C cohorts combined (Safety Population) 
Table 14.1.6d 
Summary of Prior Medication by ATC Classification and preferred 
term – Part D (Safety Population) 
Table 14.1.6de 
Summary of Prior Medication by ATC Classification and preferred 
term – Part D Extension (Safety Population) 
Table 14.1.6e 
Summary of Prior Medication by ATC Classification and preferred 
term – Part E (Safety Population) 
Table 14.1.7a 
Summary of Concomitant Medication by ATC Classification and 
preferred term – Part A (Safety Population) 
Table 14.1.7b 
Summary of Concomitant Medication by ATC Classification and 
preferred term – Part B and Part C (Safety Population) 
Table 14.1.7c 
Summary of Concomitant Medication by ATC Classification and 
preferred term – Part B and Part C cohorts combined (Safety 
Population) 
Table 14.1.7d 
Summary of Concomitant Medication by ATC Classification and 
preferred term – Part D (Safety Population) 
Table 14.1.7de 
Summary of Concomitant Medication by ATC Classification and 
preferred term – Part D Extension (Safety Population) 
Table 14.1.7e 
Summary of Concomitant Medication by ATC Classification and 
preferred term – Part E (Safety Population) 
Section 14.2 
Pharmacokinetic Data Summaries 
Table 14.2.1a 
Summary of AT-007 Plasma Concentrations – Part A (PK 
Population) 
Table 14.2.1b 
Summary of AT-007 Plasma Concentrations – Part B (PK 
Population) 
Table 14.2.1c 
Summary of AT-007 Plasma Concentrations – Part C (PK 
Population) 
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Table 14.2.1d 
Summary of AT-007 Plasma Concentrations – Part D (PK 
Population) 
Table 14.2.1de 
Summary of AT-007 Plasma Concentrations – Part D Extension (PK 
Population) 
Table 14.2.1e 
Summary of AT-007 Plasma Concentrations – Part E (PK 
Population) 
Table 14.2.2a 
Summary of AT-007 Plasma Pharmacokinetic Parameters – Part A 
(PK Population) 
Table 14.2.2b 
Summary of AT-007 Plasma Pharmacokinetic Parameters – Part B 
(PK Population) 
Table 14.2.2c 
Summary of AT-007 Plasma Pharmacokinetic Parameters – Part C 
(PK Population) 
Table 14.2.2d 
Summary of AT-007 Plasma Pharmacokinetic Parameters – Part D 
(PK Population) 
Table 14.2.2de 
Summary of AT-007 Plasma Pharmacokinetic Parameters – Part D 
Extension (PK Population) 
Table 14.2.2e 
Summary of AT-007 Plasma Pharmacokinetic Parameters – Part E 
(PK Population) 
Figure 14.2.1a 
Plot of Mean (+/-SD) Plasma Concentrations of AT-007 over Time – 
Part A (PK Population) 
Figure 14.2.1b 
Plot of Mean (+/-SD) Plasma Concentrations of AT-007 over Time – 
Part B and Part C (PK Population) 
Figure 14.2.1c 
Plot of Mean (+/-SD) Plasma Concentrations of AT-007 over Time – 
Part B and Part C cohorts combined (PK Population) 
Figure 14.2.1d 
Plot of Mean (+/-SD) Plasma Concentrations of AT-007 over Time – 
Part D (PK Population) 
Figure 14.2.1de 
Plot of Mean (+/-SD) Plasma Concentrations of AT-007 over Time – 
Part D Extension (PK Population) 
Figure 14.2.1e 
Plot of Mean (+/-SD) Plasma Concentrations of AT-007 over Time – 
Part E (PK Population) 
Figure 14.2.2a 
Spaghetti Plot of Concentrations vs Time with Average Profile 
Overlaid by Day – Part A (PK Population) 
Figure 14.2.2b 
Spaghetti Plot of Concentrations vs Time with Average Profile 
Overlaid by Day – Part B and Part C(PK Population) 
Figure 14.2.2c 
Spaghetti Plot of Concentrations vs Time with Average Profile 
Overlaid by Day – Part B and Part C cohorts combined (PK 
Population) 
Figure 14.2.2d 
Spaghetti Plot of Concentrations vs Time with Average Profile 
Overlaid by Day – Part D (PK Population) 
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Figure 14.2.2de 
Spaghetti Plot of Concentrations vs Time with Average Profile 
Overlaid by Day – Part D Extension (PK Population) 
Figure 14.2.2e 
Spaghetti Plot of Concentrations vs Time with Average Profile 
Overlaid by Day – Part E (PK Population) 
Table 14.2.3a 
Summary of AT-007 Amount Excreted in Urine – Part A (PK 
Population) 
Table 14.2.3d 
Summary of AT-007 Amount Excreted in Urine – Part D (PK 
Population) 
Table 14.2.4a 
Summary of AT-007 Urine Pharmacokinetic Parameters – Part A 
(PK Population) 
Table 14.2.4d 
Summary of AT-007 Urine Pharmacokinetic Parameters – Part D 
(PK Population) 
Table 14.2.5c 
Summary of CSF Concentration of AT-007 - Part C (PK Population) 
Table 14.2.6a 
Statistical Analysis of Dose Proportionality after Single dose - Part A 
(PK Population) 
Table 14.2.6b 
Statistical Analysis of Dose Proportionality after Multiple dose – Part 
B and Part C (PK Population) 
Table 14.2.6d1 
Statistical Analysis of Dose Proportionality after Single dose – Part 
D (PK Population) 
Table 14.2.6d2 
Statistical Analysis of Dose Proportionality after Multiple dose – Part 
D (PK Population) 
Table 14.2.6de 
Statistical Analysis of Dose Proportionality after Multiple dose – Part 
D Extension (PK Population) 
Table 14.2.6e1 
Statistical Analysis of Dose Proportionality after Single dose – Part E 
(PK Population) 
Table 14.2.6e2 
Statistical Analysis of Dose Proportionality after Multiple dose – Part 
E (PK Population) 
Table 14.2.7.1.1d 
Summary of Plasma Galactitol Results – Part D (Safety Population) 
Table 14.2.7.1.2d 
Summary of Plasma Galactose Results – Part D (Safety Population) 
Table 14.2.7.1.3d 
Summary of Whole blood Gal-1P Results – Part D (Safety 
Population) 
Table 14.2.7.1.1e 
Summary of Plasma Galactitol Results – Part E (Safety Population) 
Table 14.2.7.1.2e 
Summary of Plasma Galactose Results – Part E (Safety Population) 
Table 14.2.7.1.3e 
Summary of Whole blood Gal-1P Results – Part E (Safety 
Population) 
Figure 14.2.7.1.1d 
Plot of Mean (+/-SD) Plasma Galactitol Concentrations over Time – 
Part D (PK Population) 
Figure 14.2.7.1.2d 
Plot of Mean (+/-SD) Plasma Galactose Concentrations over Time – 
Part D (PK Population) 
Figure 14.2.7.1.3d 
Plot of Mean (+/-SD) Whole blood Gal-1P Concentrations over Time 
– Part D (PK Population) 
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Figure 14.2.7.1.1e 
Plot of Mean (+/-SD) Plasma Galactitol Concentrations  over Time – 
Part E (PK Population) 
Figure 14.2.7.1.2e 
Plot of Mean (+/-SD) Plasma Galactose Concentrations over Time – 
Part E (PK Population) 
Figure 14.2.7.1.3e 
Plot of Mean (+/-SD) Whole blood Gal-1P Concentrations over Time 
– Part E (PK Population) 
Table 14.2.7.2d 
Summary of Plasma Galactitol Results by Subgroup (Gender) – Part 
D (Safety Population) 
Table 14.2.7.2e 
Summary of Plasma Galactitol Results by Subgroup (Gender) – Part 
E (Safety Population) 
Table 14.2.7.3d 
Summary of Plasma Galactitol Results by Subgroup (Age) – Part D 
(Safety Population) 
Table 14.2.7.3e 
Summary of Plasma Galactitol Results by Subgroup (Age) – Part E 
(Safety Population) 
Table 14.2.7.4d 
Summary of Plasma Galactitol Results by Subgroup (BMI) – Part D 
(Safety Population) 
Table 14.2.7.4e 
Summary of Plasma Galactitol Results by Subgroup (BMI) – Part E 
(Safety Population) 
Table 14.2.7.5d 
Summary of Plasma Galactitol Results by Subgroup (Enzyme 
Activity) – Part D (Safety Population) 
Table 14.2.7.5e 
Summary of Plasma Galactitol Results by Subgroup (Enzyme 
Activity) – Part E (Safety Population) 
Figure 14.2.7.2d 
Forest plot of Plasma Galactitol Results by Subgroup at Day 32– Part 
D (Safety Population) 
Figure 14.2.7.2e 
Forest plot of Plasma Galactitol Results by Subgroup at Day 32 – 
Part E (Safety Population) 
Table 14.2.7.6d 
Summary of Change in Allele due to Gene mutation – Part D (Safety 
Population) 
Table 14.2.7.6e 
Summary of Change in Allele due to Gene mutation – Part E (Safety 
Population) 
Section 14.3 
Safety Data Summaries 
Section 14.3.1 
Displays of Adverse Events 
Table 14.3.1.1a 
Overall Summary of Treatment-Emergent Adverse Events – Part A 
(Safety Population) 
Table 14.3.1.1b 
Overall Summary of Treatment-Emergent Adverse Events – Part B 
and Part C (Safety Population) 
Table 14.3.1.1c 
Overall Summary of Treatment-Emergent Adverse Events – Part B 
and Part C cohorts combined (Safety Population) 
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Table 14.3.1.1d 
Overall Summary of Treatment-Emergent Adverse Events – Part D 
(Safety Population) Part D 
Table 14.3.1.1de 
Overall Summary of Treatment-Emergent Adverse Events – Part D 
Extension (Safety Population) Part D Extension 
Table 14.3.1.1e 
Overall Summary of Treatment-Emergent Adverse Events – Part E 
(Safety Population) Part E 
Table 14.3.1.2a 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term – Part A (Safety Population) 
Table 14.3.1.2b 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term – Part B and Part C (Safety Population) 
Table 14.3.1.2c 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term – Part B and Part C cohorts combined 
(Safety Population) 
Table 14.3.1.2d 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term – Part D (Safety Population) 
Table 14.3.1.2de 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term – Part D Extension (Safety Population) 
Table 14.3.1.2e 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term – Part E (Safety Population) 
Table 14.3.1.3a 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term by Maximum Severity Grade – Part A 
(Safety Population) 
Table 14.3.1.3b 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term by Maximum Severity Grade – Part B and 
Part C (Safety Population) 
Table 14.3.1.3c 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term by Maximum Severity Grade – Part B and 
Part C cohorts combined (Safety Population) 
Table 14.3.1.3d 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term by Maximum Severity Grade – Part D 
(Safety Population) 
Table 14.3.1.3de 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term by Maximum Severity Grade – Part D 
Extension (Safety Population) 
Table 14.3.1.3e 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term by Maximum Severity Grade – Part E 
(Safety Population) 
Table 14.3.1.4a 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class, Preferred Term and Closest Relationship to Study Drug – Part 
A (Safety Population) 
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Table 14.3.1.4b 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class, Preferred Term and Closest Relationship to Study Drug – Part 
B and Part C (Safety Population) 
Table 14.3.1.4c 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class, Preferred Term and Closest Relationship to Study Drug – Part 
B and Part C cohorts combined (Safety Population) 
Table 14.3.1.4d 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class, Preferred Term and Closest Relationship to Study Drug – Part 
D (Safety Population) 
Table 14.3.1.4de 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class, Preferred Term and Closest Relationship to Study Drug – Part 
D Extension (Safety Population) 
Table 14.3.1.4e 
Summary of Treatment-Emergent Adverse Events by System Organ 
Class, Preferred Term and Closest Relationship to Study Drug – Part 
E (Safety Population) 
Section 14.3.2 
Listings of Deaths, Other Serious and Certain Significant 
Adverse Events 
Table 14.3.2.1a 
Listing of Adverse Events Leading to Death – Part A (Safety 
Population) 
Table 14.3.2.1b 
Listing of Adverse Events Leading to Death – Part B (Safety 
Population) 
Table 14.3.2.1c 
Listing of Adverse Events Leading to Death – Part C (Safety 
Population) 
Table 14.3.2.1d 
Listing of Adverse Events Leading to Death – Part D (Safety 
Population) 
Table 14.3.2.1de 
Listing of Adverse Events Leading to Death – Part D Extension 
(Safety Population) 
Table 14.3.2.1e 
Listing of Adverse Events Leading to Death – Part E (Safety 
Population) 
Table 14.3.2.2a 
Listing of Serious Adverse Events – Part A (Safety Population) 
Table 14.3.2.2b 
Listing of Serious Adverse Events – Part B (Safety Population) 
Table 14.3.2.2c 
Listing of Serious Adverse Events – Part C (Safety Population) 
Table 14.3.2.2d 
Listing of Serious Adverse Events – Part D (Safety Population) 
Table 14.3.2.2de 
Listing of Serious Adverse Events – Part D Extension (Safety 
Population) 
Table 14.3.2.2e 
Listing of Serious Adverse Events – Part E (Safety Population) 
Table 14.3.2.3a 
Listing of Adverse Events Resulting in Discontinuation of Study or 
Study Drug – Part A (Safety Population) 
Table 14.3.2.3b 
Listing of Adverse Events Resulting in Discontinuation of Study or 
Study Drug – Part B (Safety Population) 
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Table 14.3.2.3c 
Listing of Adverse Events Resulting in Discontinuation of Study or 
Study Drug – Part C (Safety Population) 
Table 14.3.2.3d 
Listing of Adverse Events Resulting in Discontinuation of Study or 
Study Drug – Part D (Safety Population) 
Table 14.3.2.3de 
Listing of Adverse Events Resulting in Discontinuation of Study or 
Study Drug – Part D Extension (Safety Population) 
Table 14.3.2.3e 
Listing of Adverse Events Resulting in Discontinuation of Study or 
Study Drug – Part E (Safety Population) 
Section 14.3.4 
Abnormal Laboratory Value Listing 
Table 14.3.4.1a 
Listing of Individual Subjects with Abnormal Clinical Laboratory 
Values – Part A (Safety Population) 
Table 14.3.4.1b 
Listing of Individual Subjects with Abnormal Clinical Laboratory 
Values – Part B (Safety Population) 
Table 14.3.4.1c 
Listing of Individual Subjects with Abnormal Clinical Laboratory 
Values – Part C (Safety Population) 
Table 14.3.4.1d 
Listing of Individual Subjects with Abnormal Clinical Laboratory 
Values – Part D (Safety Population) 
Table 14.3.4.1de 
Listing of Individual Subjects with Abnormal Clinical Laboratory 
Values – Part D Extension (Safety Population) 
Table 14.3.4.1e 
Listing of Individual Subjects with Abnormal Clinical Laboratory 
Values – Part E (Safety Population) 
Table 14.3.4.2a 
Summary of Observed Values and Change from Baseline Clinical 
Laboratory Results by Category and Test – Part A (Safety 
Population) 
Table 14.3.4.2b 
Summary of Observed Values and Change from Baseline Clinical 
Laboratory Results by Category and Test – Part B and Part C (Safety 
Population) 
Table 14.3.4.2c 
Summary of Observed Values and Change from Baseline Clinical 
Laboratory Results by Category and Test – Part B and Part C cohorts 
combined (Safety Population) 
Table 14.3.4.2d 
Summary of Observed Values and Change from Baseline Clinical 
Laboratory Results by Category and Test – Part D (Safety 
Population) 
Table 14.3.4.2de 
Summary of Observed Values and Change from Baseline Clinical 
Laboratory Results by Category and Test – Part D Extension (Safety 
Population) 
Table 14.3.4.2e 
Summary of Observed Values and Change from Baseline Clinical 
Laboratory Results by Category and Test – Part E (Safety 
Population) 
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Table 14.3.4.3a 
Shift from Baseline in Clinical Laboratory Results – Part A (Safety 
Population) 
Table 14.3.4.3b 
Shift from Baseline in Clinical Laboratory Results – Part B and Part 
C (Safety Population) 
Table 14.3.4.3c 
Shift from Baseline in Clinical Laboratory Results – Part B and Part 
C cohorts combined (Safety Population) 
Table 14.3.4.3d 
Shift from Baseline in Clinical Laboratory Results – Part D (Safety 
Population) 
Table 14.3.4.3de 
Shift from Baseline in Clinical Laboratory Results – Part D 
Extension (Safety Population) 
Table 14.3.4.3e 
Shift from Baseline in Clinical Laboratory Results – Part E (Safety 
Population) 
Section 14.3.5 
Additional Safety Data Summaries 
Table 14.3.5.1a 
Absolute and Change from Baseline Vital Signs by Visits – Part A 
(Safety Population) 
Table 14.3.5.1b 
Absolute and Change from Baseline Vital Signs by Visits – Part B 
and Part C (Safety Population) 
Table 14.3.5.1c 
Absolute and Change from Baseline Vital Signs by Visits – Part B 
and Part C cohorts combined (Safety Population) 
Table 14.3.5.1d 
Absolute and Change from Baseline Vital Signs by Visits – Part D 
(Safety Population) 
Table 14.3.5.1de 
Absolute and Change from Baseline Vital Signs by Visits – Part D 
Extension (Safety Population) 
Table 14.3.5.1e 
Absolute and Change from Baseline Vital Signs by Visits – Part E 
(Safety Population) 
Table 14.3.5.2a 
Summary of Observed Values and Change from Baseline for 
Continuous ECG Data – Part A (Safety Population) 
Table 14.3.5.2b 
Summary of Observed Values and Change from Baseline for 
Continuous ECG Data – Part B and Part C (Safety Population) 
Table 14.3.5.2c 
Summary of Observed Values and Change from Baseline for 
Continuous ECG Data – Part B and Part C cohorts combined (Safety 
Population) 
Table 14.3.5.2d 
Summary of Observed Values and Change from Baseline for 
Continuous ECG Data – Part D (Safety Population) 
Table 14.3.5.2de 
Summary of Observed Values and Change from Baseline for 
Continuous ECG Data – Part D Extension (Safety Population) 
Table 14.3.5.2e 
Summary of Observed Values and Change from Baseline for 
Continuous ECG Data – Part E (Safety Population) 
 
 
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Listing/Figure 
Number 
Listing/Figure Name 
Section 16.1.7 
Randomization 
Listing 16.1.7.1a 
Randomization Allocation – Part A (Safety Population) 
Listing 16.1.7.1b 
Randomization Allocation – Part B (Safety Population) 
Listing 16.1.7.1c 
Randomization Allocation – Part C (Safety Population) 
Listing 16.1.7.1d 
Randomization Allocation – Part D (Safety Population) 
Listing 16.1.7.1de 
Randomization Allocation – Part D Extension (Safety Population) 
Listing 16.1.7.1e 
Randomization Allocation – Part E (Safety Population) 
Section 16.2.1 
Discontinued Subjects 
Listing 16.2.1a 
Subject Disposition – Part A (All Screened Population) 
Listing 16.2.1b 
Subject Disposition – Part B (All Screened Population) 
Listing 16.2.1c 
Subject Disposition – Part C (All Screened Population) 
Listing 16.2.1d 
Subject Disposition – Part D (All Screened Population) 
Listing 16.2.1de 
Subject Disposition – Part D Extension (All Screened Population) 
Listing 16.2.1e 
Subject Disposition – Part E (All Screened Population) 
Section 16.2.2 
Protocol Deviations 
Listing 16.2.2a 
Protocol Deviations – Part A (Safety Population) 
Listing 16.2.2b 
Protocol Deviations – Part B (Safety Population) 
Listing 16.2.2c 
Protocol Deviations – Part C (Safety Population) 
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Listing 16.2.2d 
Protocol Deviations – Part D (Safety Population) 
Listing 16.2.2de 
Protocol Deviations – Part D Extension (Safety Population) 
Listing 16.2.2e 
Protocol Deviations – Part E (Safety Population) 
Section 16.2.3 
Subjects Excluded from Analysis 
Listing 16.2.3a 
Analysis Sets – Part A (Safety Population) 
Listing 16.2.3b 
Analysis Sets – Part B (Safety Population) 
Listing 16.2.3c 
Analysis Sets – Part C (Safety Population) 
Listing 16.2.3d 
Analysis Sets – Part D (Safety Population) 
Listing 16.2.3de 
Analysis Sets – Part D Extension (Safety Population) 
Listing 16.2.3e 
Analysis Sets – Part E (Safety Population) 
Section 16.2.4 
Demographic Data 
Listing 16.2.4.1a 
Demographics Including Childbearing Potential and Screening 
Height and Weight – Part A (Safety Population) 
Listing 16.2.4.1b 
Demographics Including Childbearing Potential and Screening 
Height and Weight – Part B (Safety Population) 
Listing 16.2.4.1c 
Demographics Including Childbearing Potential and Screening 
Height and Weight – Part C (Safety Population) 
Listing 16.2.4.1d 
Demographics Including Childbearing Potential and Screening 
Height and Weight – Part D (Safety Population) 
Listing 16.2.4.1de 
Demographics Including Childbearing Potential and Screening 
Height and Weight – Part D Extension (Safety Population) 
Listing 16.2.4.1e 
Demographics Including Childbearing Potential and Screening 
Height and Weight – Part E (Safety Population) 
Listing 16.2.4.2a 
Eligibility Criteria Satisfaction – Part A (All Screened Population) 
Listing 16.2.4.2b 
Eligibility Criteria Satisfaction – Part B (All Screened Population) 
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Listing 16.2.4.2c 
Eligibility Criteria Satisfaction – Part C (All Screened Population) 
Listing 16.2.4.2d 
Eligibility Criteria Satisfaction – Part D (All Screened Population) 
Listing 16.2.4.2de 
Eligibility Criteria Satisfaction – Part D Extension (All Screened 
Population) 
Listing 16.2.4.2e 
Eligibility Criteria Satisfaction – Part E (All Screened Population) 
Listing 16.2.4.3a 
Medical and Surgical History – Part A (Safety Population) 
Listing 16.2.4.3b 
Medical and Surgical History – Part B (Safety Population) 
Listing 16.2.4.3c 
Medical and Surgical History – Part C (Safety Population) 
Listing 16.2.4.3d 
Medical and Surgical History – Part D (Safety Population) 
Listing 16.2.4.3de 
Medical and Surgical History – Part D Extension (Safety Population) 
Listing 16.2.4.3e 
Medical and Surgical History – Part E (Safety Population) 
Listing 16.2.4.4a 
Prior and Concomitant Medications – Part A (Safety Population) 
Listing 16.2.4.4b 
Prior and Concomitant Medications – Part B (Safety Population) 
Listing 16.2.4.4c 
Prior and Concomitant Medications – Part C (Safety Population) 
Listing 16.2.4.4d 
Prior and Concomitant Medications – Part D (Safety Population) 
Listing 16.2.4.4de 
Prior and Concomitant Medications – Part D Extension (Safety 
Population) 
Listing 16.2.4.4e 
Prior and Concomitant Medications – Part E (Safety Population) 
Listing 16.2.4.5a 
Concomitant Procedures – Part A (Safety Population) 
Listing 16.2.4.5b 
Concomitant Procedures – Part B (Safety Population) 
Listing 16.2.4.5c 
Concomitant Procedures – Part C (Safety Population) 
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Listing 16.2.4.5d 
Concomitant Procedures – Part D (Safety Population) 
Listing 16.2.4.5de 
Concomitant Procedures – Part D Extension (Safety Population) 
Listing 16.2.4.5e 
Concomitant Procedures – Part E (Safety Population) 
Section 16.2.5 
Compliance and/or Drug Concentration Data 
Listing 16.2.5.1a 
Study Drug Dosing Record – Part A (Safety Population) 
Listing 16.2.5.1b 
Study Drug Dosing Record – Part B (Safety Population) 
Listing 16.2.5.1c 
Study Drug Dosing Record – Part C (Safety Population) 
Listing 16.2.5.1d 
Study Drug Dosing Record – Part D (Safety Population) 
Listing 16.2.5.1de 
Study Drug Dosing Record – Part D Extension (Safety Population) 
Listing 16.2.5.1e 
Study Drug Dosing Record – Part E (Safety Population) 
Listing 16.2.5.2d 
Treatment Compliance – Part D (Safety Population) 
Listing 16.2.5.2de 
Treatment Compliance – Part D Extension (Safety Population) 
Listing 16.2.5.2e 
Treatment Compliance – Part E (Safety Population) 
Listing 16.2.5.3a 
Meal – Part A (Safety Population) 
Listing 16.2.5.3b 
Meal – Part B (Safety Population) 
Listing 16.2.5.3c 
Meal – Part C (Safety Population) 
Listing 16.2.5.3d 
Meal – Part D (Safety Population) 
Listing 16.2.5.3de 
Meal – Part D Extension (Safety Population) 
Listing 16.2.5.3e 
Meal – Part E (Safety Population) 
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Listing 16.2.5.4a 
Individual Blood Sampling Time and Plasma Concentrations of AT-
007 – Part A (PK Population) 
Listing 16.2.5.4b 
Individual Blood Sampling Time and Plasma Concentrations of AT-
007 – Part B (PK Population) 
Listing 16.2.5.4c 
Individual Blood Sampling Time and Plasma Concentrations of AT-
007 – Part C (PK Population) 
Listing 16.2.5.4d 
Individual Blood Sampling Time and Plasma Concentrations of AT-
007 – Part D (PK Population) 
Listing 16.2.5.4de 
Individual Blood Sampling Time and Plasma Concentrations of AT-
007 – Part D Extension (PK Population) 
Listing 16.2.5.4e 
Individual Blood Sampling Time and Plasma Concentrations of AT-
007 – Part E (PK Population) 
Listing 16.2.5.5a 
Individual Urine Collection Intervals, Urine Volumes Concentrations 
and Amounts of AT-007 – Part A (PK Population) 
Listing 16.2.5.5d 
Individual Urine Collection Intervals, Urine Volumes Concentrations 
and Amounts of AT-007 – Part D (PK Population) 
Listing 16.2.5.6c 
Individual CSF Sampling Time and Concentrations of AT-007 - Part 
C (PK Population) 
Section 16.2.6 
Individual Pharmacokinetic Response Data 
Listing 16.2.6.1a 
Individual Plasma PK Parameters – Part A (PK Population) 
Listing 16.2.6.1b 
Individual Plasma PK Parameters – Part B (PK Population) 
Listing 16.2.6.1c 
Individual Plasma PK Parameters – Part C (PK Population) 
Listing 16.2.6.1d1 
Individual Plasma PK Parameters after Single dose – Part D (PK 
Population) 
Listing 16.2.6.1d2 
Individual Plasma PK Parameters after Multiple dose – Part D (PK 
Population) 
Listing 16.2.6.1de 
Individual Plasma PK Parameters – Part D Extension (PK 
Population) 
Listing 16.2.6.1e1 
Individual Plasma PK Parameters after Single dose – Part E (PK 
Population) 
Listing 16.2.6.1e2 
Individual Plasma PK Parameters after Multiple dose – Part E (PK 
Population) 
Listing 16.2.6.2a 
Individual Urine PK Parameters – Part A (PK Population) 
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Listing 16.2.6.2d 
Individual Urine PK Parameters – Part D (PK Population) 
Figure 16.2.5.1a 
Plots of Individual Plasma Concentrations of AT-007 over Time – 
Part A (PK Population) 
Figure 16.2.5.1b 
Plots of Individual Plasma Concentrations of AT-007 over Time – 
Part B and Part C (PK Population) 
Figure 16.2.5.1c 
Plots of Individual Plasma Concentrations of AT-007 over Time – 
Part B and Part C cohorts combined(PK Population) 
Figure 16.2.5.1d 
Plots of Individual Plasma Concentrations of AT-007 over Time – 
Part D (PK Population) 
Figure 16.2.5.1de 
Plots of Individual Plasma Concentrations of AT-007 over Time – 
Part D Extension (PK Population) 
Figure 16.2.5.1e 
Plots of Individual Plasma Concentrations of AT-007 over Time – 
Part E (PK Population) 
Section 16.2.7 
Adverse Event Listings 
Listing 16.2.7.1a 
All Adverse Events – Part A (Safety Population) 
Listing 16.2.7.1b 
All Adverse Events – Part B (Safety Population) 
Listing 16.2.7.1c 
All Adverse Events – Part C (Safety Population) 
Listing 16.2.7.1d 
All Adverse Events – Part D (Safety Population) 
Listing 16.2.7.1de 
All Adverse Events – Part D Extension (Safety Population) 
Listing 16.2.7.1e 
All Adverse Events – Part E (Safety Population) 
Listing 16.2.7.2a 
Verbatim to Preferred Term Mapping of All Adverse Events – Part A 
Listing 16.2.7.2b 
Verbatim to Preferred Term Mapping of All Adverse Events – Part B 
and Part C 
Listing 16.2.7.2c 
Verbatim to Preferred Term Mapping of All Adverse Events – Part B 
and Part C cohorts combined 
Listing 16.2.7.2d 
Verbatim to Preferred Term Mapping of All Adverse Events – Part D 
Listing 16.2.7.2de 
Verbatim to Preferred Term Mapping of All Adverse Events – Part D 
Extension 
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Listing 16.2.7.2e 
Verbatim to Preferred Term Mapping of All Adverse Events – Part E 
Section 16.2.8 
Individual Laboratory Measurements by Subject 
Listing 16.2.8.1a 
Normal Ranges for Laboratory Data – Part A 
Listing 16.2.8.1b 
Normal Ranges for Laboratory Data – Part B and Part C 
Listing 16.2.8.1c 
Normal Ranges for Laboratory Data – Part B and Part C cohorts 
combined 
Listing 16.2.8.1d 
Normal Ranges for Laboratory Data – Part D 
Listing 16.2.8.1de 
Normal Ranges for Laboratory Data – Part D Extension 
Listing 16.2.8.1e 
Normal Ranges for Laboratory Data – Part E 
Listing 16.2.8.2a 
Clinical Laboratory Data by Category – Part A (Safety Population) 
Listing 16.2.8.2b 
Clinical Laboratory Data by Category – Part B (Safety Population) 
Listing 16.2.8.2c 
Clinical Laboratory Data by Category – Part C (Safety Population) 
Listing 16.2.8.2d 
Clinical Laboratory Data by Category – Part D (Safety Population) 
Listing 16.2.8.2de 
Clinical Laboratory Data by Category – Part D Extension (Safety 
Population) 
Listing 16.2.8.2e 
Clinical Laboratory Data by Category – Part E (Safety Population) 
Listing 16.2.8.3a 
Urine Drug Screen/Drugs of Abuse – Part A (Safety Population) 
Listing 16.2.8.3b 
Urine Drug Screen/Drugs of Abuse – Part B (Safety Population) 
Listing 16.2.8.3c 
Urine Drug Screen/Drugs of Abuse – Part C (Safety Population) 
Listing 16.2.8.3d 
Urine Drug Screen/Drugs of Abuse – Part D (Safety Population) 
Listing 16.2.8.3de 
Urine Drug Screen/Drugs of Abuse – Part D Extension (Safety 
Population) 
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Listing 16.2.8.3e 
Urine Drug Screen/Drugs of Abuse – Part E (Safety Population) 
Listing 16.2.8.4a 
Pregnancy and Follicle-Stimulating Hormone Tests (Women of 
Child-bearing Potential only) – Part A (Safety Population) 
Listing 16.2.8.4b 
Pregnancy and Follicle-Stimulating Hormone Tests (Women of 
Child-bearing Potential only) – Part B (Safety Population) 
Listing 16.2.8.4c 
Pregnancy and Follicle-Stimulating Hormone Tests (Women of 
Child-bearing Potential only) – Part C (Safety Population) 
Listing 16.2.8.4d 
Pregnancy and Follicle-Stimulating Hormone Tests (Women of 
Child-bearing Potential only) – Part D (Safety Population) 
Listing 16.2.8.4de 
Pregnancy and Follicle-Stimulating Hormone Tests (Women of 
Child-bearing Potential only) – Part D Extension (Safety Population) 
Listing 16.2.8.4e 
Pregnancy and Follicle-Stimulating Hormone Tests (Women of 
Child-bearing Potential only) – Part E (Safety Population) 
Listing 16.2.8.5a 
Serology Results – Part A (Safety Population) 
Listing 16.2.8.5b 
Serology Results – Part B (Safety Population) 
Listing 16.2.8.5c 
Serology Results – Part C (Safety Population) 
Listing 16.2.8.5d 
Serology Results – Part D (Safety Population) 
Listing 16.2.8.5de 
Serology Results – Part D Extension (Safety Population) 
Listing 16.2.8.5e 
Serology Results – Part E (Safety Population) 
Listing 16.2.8.6d 
Biomarkers Result – Part D (Safety Population) 
Listing 16.2.8.6e 
Biomarkers Result – Part E (Safety Population) 
Listing 16.2.8.7d 
Urine Galactitol – Part D (Safety Population) 
Listing 16.2.8.7e 
Urine Galactitol – Part E (Safety Population) 
Section 16.2.9 
Other Safety Data by Subject 
Listing 16.2.9.1a 
Vital Signs – Part A (Safety Population) 
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Listing 16.2.9.1b 
Vital Signs – Part B (Safety Population) 
Listing 16.2.9.1c 
Vital Signs – Part C (Safety Population) 
Listing 16.2.9.1d 
Vital Signs – Part D (Safety Population) 
Listing 16.2.9.1de 
Vital Signs – Part D Extension (Safety Population) 
Listing 16.2.9.1e 
Vital Signs – Part E (Safety Population) 
Listing 16.2.9.2a 
Weight and BMI – Part A (Safety Population) 
Listing 16.2.9.2b 
Weight and BMI – Part B (Safety Population) 
Listing 16.2.9.2c 
Weight and BMI – Part C (Safety Population) 
Listing 16.2.9.2d 
Weight and BMI – Part D (Safety Population) 
Listing 16.2.9.2de 
Weight and BMI – Part D Extension (Safety Population) 
Listing 16.2.9.2e 
Weight and BMI – Part E (Safety Population) 
Listing 16.2.9.3a 
Electrocardiogram Results – Part A (Safety Population) 
Listing 16.2.9.3b 
Electrocardiogram Results – Part B (Safety Population) 
Listing 16.2.9.3c 
Electrocardiogram Results – Part C (Safety Population) 
Listing 16.2.9.3d 
Electrocardiogram Results – Part D (Safety Population) 
Listing 16.2.9.3de 
Electrocardiogram Results – Part D Extension (Safety Population) 
Listing 16.2.9.3e 
Electrocardiogram Results – Part E (Safety Population) 
Listing 16.2.9.4a 
Physical Examination Findings – Part A (Safety Population) 
Listing 16.2.9.4b 
Physical Examination Findings – Part B (Safety Population) 
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Listing 16.2.9.4c 
Physical Examination Findings – Part C (Safety Population) 
Listing 16.2.9.4d 
Physical Examination Findings – Part D (Safety Population) 
Listing 16.2.9.4de 
Physical Examination Findings – Part D Extension (Safety 
Population) 
Listing 16.2.9.4e 
Physical Examination Findings – Part E (Safety Population) 
Listing 16.2.9.5a 
Investigator Comments – Part A(Safety Population) 
Listing 16.2.9.5b 
Investigator Comments – Part B (Safety Population) 
Listing 16.2.9.5c 
Investigator Comments – Part C (Safety Population) 
Listing 16.2.9.5d 
Investigator Comments – Part D (Safety Population) 
Listing 16.2.9.5de 
Investigator Comments – Part D Extension (Safety Population) 
Listing 16.2.9.5e 
Investigator Comments – Part E (Safety Population) 
 
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