A Phase 2a Double-blind, Placebo-controlled, Parallel Study of PH94B Nasal Spray in the Treatment of Adjustment Disorder With Anxiety
Phase: PHASE2
Conditions: Adjustment Disorder With Anxious Mood
Sponsor: VistaGen Therapeutics, Inc.

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PROTOCOL
PRODUCT NAME/NUMBER: 
PH94B Nasal Spray 
PROTOCOL NUMBER: 
PH94B-CL029 
 
 
NCT NUMBER:  
NCT04404192 
DEVELOPMENT PHASE: 
2a 
PROTOCOL TITLE: 
A Phase 2a Double-blind, Placebo-controlled, Parallel 
Study of PH94B Nasal Spray in the Treatment of Anxiety 
in Adults with Adjustment Disorder with Anxiety 
PROTOCOL DATE: 
Final, Version 2.0, 30-Aug-2021 
SPONSORED BY: 
VistaGen Therapeutics, Inc. 
343 Allerton Avenue 
South San Francisco, CA 94080, USA 
CONTRACT RESEARCH 
ORGANIZATION: 
Premier Research  
3800 Paramount Parkway, Suite 400 
Morrisville, NC 27560, USA 
 
This study will be performed in compliance with ICH Good Clinical Practices and applicable 
regulatory requirements, including the archiving of essential documents. Information contained in 
this protocol is confidential in nature, and may not be used, divulged, published, or otherwise 
disclosed to others except to the extent necessary to obtain approval of the institutional review 
board or independent ethics committee, or as required by law. Persons to whom this information 
is disclosed should be informed that it is confidential and may not be further disclosed without the 
express permission of sponsor. 

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1. APPROVAL SIGNATURES 
PROTOCOL NUMBER: 
PH94B-CL029 
PROTOCOL TITLE: 
A Phase 2a Double-blind, Placebo-controlled, Parallel Study of 
PH94B Nasal Spray in the Treatment of Anxiety in Adults with 
Adjustment Disorder with Anxiety 
I, the undersigned, have read this protocol and confirm that to the best of my knowledge it 
accurately describes the planned conduct of the study. 
SIGNATURE
DATE:
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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2.
PROTOCOL SUMMARY
2.1. Synopsis 
PRODUCT 
NAME/NUMBER 
PH94B Nasal Spray
PROTOCOL 
NUMBER 
PH94B-CL029 
DEVELOPMENT 
PHASE 
2a
PROTOCOL TITLE 
A Phase 2a Double-blind, Placebo-controlled, Parallel Study of PH94B Nasal Spray in 
the Treatment of Anxiety in Adults with Adjustment Disorder with Anxiety 
INDICATION
Adjustment disorderwith anxiety
OBJECTIVES 
Primary: 
The primary objective of the study is to evaluate the efficacy of PH94B Nasal Spray 
(PH94B) administered 4 times per day over 4 weeks for the treatment of anxiety in adult 
subjects with adjustment disorder with anxiety (AjDA). 
Secondary: 
The secondary objective of the study is to evaluate the safety and tolerability of PH94B. 
Exploratory: 
The exploratory objective of the study is to evaluate efficacy of PH94B over time during 
the 4-week treatment period. 
RATIONALE
The study is designed to evaluate the safety, tolerability, and efficacy of the 
administration of PH94B as a treatment for anxiety in adults with AjDA. 
STUDY DESIGN 
This is a Phase 2a double-blind, placebo-controlled, parallel group clinical study in adult 
subjects diagnosed with AjDA. Subjects diagnosed with AjDA by the Diagnostic and 
Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria and have a 
clinician-rated Hamilton Anxiety Scale (HAM-A) score of 20 or greater are to be 
enrolled. 
Experimental procedures: 
Subject participation in the study will last a total of 6 to 10 weeks, depending on the 
duration of the screening period and whether they need a washout of concomitant 
anxiolytics. Upon signing an investigation review board approved informed consent, all 
subjects will complete Visit 1 (Screening) and enter a screening period lasting 7 to 
35 days that could include tapering of concomitant anxiolytics, if necessary. Screening 
(Visit 1) will consist of safety assessments (medical history, physical examination, 
laboratory tests [chemistry and blood], electrocardiogram [ECG], urine drug screen, and 
urine pregnancy test [if appropriate]) and psychiatric assessments (Mini-International 
Neuropsychiatric Interview [MINI], HAM-A, Montgomery-Asberg Depression Rating 
Scale [MADRS], Clinical Global Impression - Severity Scale [CGI-S], Columbia-Suicide 
Severity Rating Scale [C-SSRS], and Liebowitz Social Anxiety Scale [LSAS]) to 
determine eligibility. Subjects will then return to complete Visit 2 (Baseline). At this visit, 
subjects will complete all psychiatric assessments (HAM-A, MADRS, C-SSRS, 
Adjustment Disorder New Module Scale [ADNM], International Adjustment Disorder 
Questionnaire [IADQ], and CGI-S), vital signs, laboratory tests (chemistry and blood), 
urine drug screen, and urine pregnancy test (if appropriate). If the subject continues to 
meet the inclusion criteria and none of the exclusion criteria, the subject will be 
randomized 1:1 to PH94B or placebo. The subject will be trained on using the 

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investigational product (IP) and will be dispensed a 1-week supply of PH94B or placebo. 
Subjects will then commence 4 weeks of double-blind treatment with the randomized IP 
4 times per day. 
Subjects will return for weekly site visits (Visits 3, 4, and 5), in which the subject will 
return the IP vials dispensed at the previous visit and receive new vials. Concomitant 
medications and adverse events (AEs) will be recorded. During these visits, the HAM-A, 
Patient Global Impression of Change (PGI-C), Clinical Global Impression - Improvement 
(CGI-I), CGI-S, and C-SSRS will be completed. Vital signs will be collected, and nasal 
passages will be examined. 
When the subject returns for Visit 6, besides the assessments completed at Visits 3 
through 5, the subjects will complete the MADRS, ADNM, and IADQ; and have a 
physical examination, ECG, laboratory tests (chemistry and blood), urinalysis, urine drug 
screen, and urine pregnancy test conducted. Any remaining IP vials will be collected. The 
subject will then come back after a 1-week washout period for the Follow-up visit 
(Visit 7). During this visit, AEs and concomitant medications since the last visit will be 
collected and the HAM-A, C-SSRS, and the 20-item Physician Withdrawal Checklist 
(PWC-20) will be completed. 
For each visit following Baseline (Visit 2), a ± 2-day window will be allowed. 
Safety considerations: 
Safety and tolerability of PH94B will be assessed and summarized through changes from 
screening in clinical laboratory values, ECGs, physical examinations, and vital sign 
assessments following exposure to PH94B, as well as by comparison of AEs reported 
during treatment with the IP. To date, limited exposure to PH94B (<2 weeks, <4 doses 
per day) in over 200 subjects has resulted in no serious AEs (SAEs) and no AEs occurring 
with statistically greater frequency for the PH94B group than for the placebo group. In 
addition, the PWC-20 will be administered to document any withdrawal effects that may 
be occurring. 
PLANNED NUMBER 
OF SUBJECTS 
Forty adult subjects will be randomized 1:1 to PH94B or placebo. 
STUDY ENTRY 
CRITERIA 
Inclusion criteria: 
1. Written informed consent provided prior to conducting any study-specific 
assessment. 
2. Male and female adults, 18 years of age. 
3. Current diagnosis of AjDA as defined in the DSM-5. 
4. Clinician-rated HAM-
Screening (Visit 1) and no greater than 
15% decrease at Baseline (Visit 2). 
5. Clinician-rated MADRS total score <20 at Screening (Visit 1) and Baseline 
(Visit 2). 
6. Clinical Global Impression - Severity Scale (CGI-
(Visit 1) and Baseline (Visit 2). 
7. Women of childbearing potential must be able to commit to the consistent and 
correct use of an effective method of birth control throughout the study and must 
also have a negative urine pregnancy test result at both Screening (Visit 1) and 
Baseline (Visit 2), prior to IP administration. Effective methods of contraception 
include condoms with spermicide, diaphragm with spermicide, hormonal 
contraceptive agents (oral, transdermal, or injectable), or implantable 
contraceptive devices. 
8. Males whose sexual partners are women of childbearing potential must commit 
to the consistent and correct use of an effective method of birth control 
throughout the study. 

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9.
Negative COVID-19 test for subjects with COVID-19 symptoms or who have 
had direct exposure to someone with a positive COVID-19 test, as determined 
by the Investigator. 
Exclusion criteria: 
1. Any history of schizophrenia or schizoaffective disorder. 
2. Any other current Axis I disorder, including, but not limited to, major depressive 
disorder, bipolar disorder, post-traumatic stress disorder, obsessive-compulsive 
disorder, premenstrual dysphoric disorder, and generalized anxiety disorder, 
which is in poor control and the primary focus of treatment. 
3. A diagnosis of social anxiety disorder. 
4. A score >60 on the LSAS at Screening (Visit 1). 
5. Subjects who meet criteria for moderate or severe alcohol or substance use 
disorder within 1 year prior to study entry. 
6. In the opinion of the Investigator, the subject has a significant risk for suicidal 
behavior during their participation in the study, or 
a.  At Screening (Visit 1): the subject scores “yes” on items 4 or 5 in the 
Suicidal Ideation section of the Columbia-Suicide Rating Scale 
(C-SSRS) with reference to a 6-month period prior to screening; or 
b.  At Screening (Visit 1): the subject has had one or more suicidal 
attempts with reference to a 2 -year period prior to screening; or 
c.  At Baseline (Visit 2): the subject scores “yes” on items 4 or 5 in the 
Suicidal Ideation section of the C-SSRS with reference to screening; or 
d.  The subject is considered to be an imminent danger to themselves or 
others. 
7. Clinically significant nasal pathology or history of significant nasal trauma, 
nasal surgery, total anosmia, or nasal septum perforation that may have damaged 
the nasal chemosensory epithelium. 
8. An acute or chronic condition, including an infectious illness, uncontrolled 
seasonal allergies at the time of the study, or significant nasal congestion that 
potentially could affect drug delivery to the nasal chemosensory epithelium. The 
Investigator may allow concomitant use of over-the-counter nasal decongestants 
as needed, since there is no apparent drug interaction between these and PH94B. 
9. Concomitant use of any anxiolytics, such as benzodiazepines, buspirone, or 
cannabinoids during the study and within 30 days of Baseline (Visit 2). 
10. Concomitant use of any over-the-counter, prescription product, or herbal 
preparation for treatment of the symptoms of anxiety during the study and within 
30 days before study entry. Selective serotonin reuptake inhibitors, serotonin-
norepinephrine reuptake inhibitors, or other approved antidepressants are 
permitted if the dose has been stable for 30 days prior to Baseline (Visit 2). 
11. Women who have a positive urine pregnancy test prior to IP administration or 
are currently breast feeding. 
12. Subjects with clinically significant abnormalities in hematology, blood 
chemistry, urinalysis, ECG, or physical examination identified at the Screening 
visit that in the clinical judgment of the Investigator, could place the subject at 
undue risk, interfere with study participation, or confound the results of the 
study. 
13. Subjects with a positive urine drug screen at either Screening (Visit 1) or 
Baseline (Visit 2). 
14. Any current clinically significant and/or uncontrolled medical condition, based 
on medical history or as evidenced in screening assessments, such as 
COVID-19, HIV, cancer, stroke, congestive heart failure, uncontrolled diabetes 
mellitus, or any other medical condition or disease that, in the clinical judgment 

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Interview Guide for the HAM-A (SIGH-A), after 4 weeks of randomized 
treatment with the study medication 
4. Population-level summary measure: Difference in mean HAM-A total score 
between PH94B-treated and placebo-treated subjects after 4 weeks of treatment 
5. Anticipated intercurrent event: Treatment discontinuation prior to the planned 
assessment time frame 
SAMPLE SIZE 
DETERMINATION 
A sample size of 40 subjects was selected based on information from published studies 
on treatments for adjustment disorder suggesting that a clinically meaningful effect size 
could be estimated using a sample size of 40. 
STUDY AND 
TREATMENT 
DURATION 
The sequence and maximum duration of the study periods will be as follows: 
1. Screening and washout: 
 
2. Treatment period: From Visit 2 (Baseline) through Visit 6 (End of Treatment) 
3. Follow-up period: Follow-up visit (Visit 7) conducted approximately 1 week 
after last treatment 
The maximum study duration for each subject is approximately 10 weeks. 
The maximum treatment duration for each subject is 4 weeks. 
 

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3.
TABLE OF CONTENTS
1.
APPROVAL SIGNATURES ............................................................................................ 2
2. PROTOCOL SUMMARY ................................................................................................ 4
2.1.
Synopsis.................................................................................................................. 4
2.2.
Schedule of Events ................................................................................................ 10
3.
TABLE OF CONTENTS................................................................................................ 11
3.1.
List of In-Text Tables ............................................................................................ 15
4. LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ....................................... 16
5. INTRODUCTION .......................................................................................................... 18
5.1.
Background and Rationale ..................................................................................... 18
5.1.1
Adjustment Disorder................................................................................... 18
5.1.2
Nasal Chemosensory Systems..................................................................... 18
5.1.3 PH94B ....................................................................................................... 19
5.2.
Clinical Experience................................................................................................ 20
5.2.1 Phase 1 Studies ........................................................................................... 20
5.2.2 Phase 2 Studies ........................................................................................... 21
5.3.
Summary of Potential Risks and Benefits ............................................................... 21
6. OBJECTIVES ................................................................................................................ 22
6.1.
Primary Objective .................................................................................................. 22
6.2.
Secondary Objectives............................................................................................. 22
6.4.
Endpoint Mapping ................................................................................................. 22
7. STUDY DESIGN ........................................................................................................... 24
7.1.
Overall Study Design and Plan............................................................................... 24
7.2.
Rationale and Discussion of Study Design .............................................................. 24
7.3.
Selection of Doses in the Study.............................................................................. 25
7.4.
Study Sites............................................................................................................ 25
7.5.
End of Study Definition ......................................................................................... 25
8. SUBJECT POPULATION .............................................................................................. 26
8.1.
Selection of Study Population ................................................................................ 26
8.2.
Study Entry Criteria ............................................................................................... 26
8.2.1 Inclusion Criteria ........................................................................................ 26
8.2.2 Exclusion Criteria ....................................................................................... 26
8.3.
Premature Subject Withdrawal ............................................................................... 28
8.4.
Subject Replacement Criteria................................................................................. 29
9. TREATMENTS.............................................................................................................. 30
9.1.
Identification of Investigational Product ................................................................. 30
9.2.
Selection of Timing of Dose for Each Subject......................................................... 30

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9.3.
Dose Adjustment Criteria ....................................................................................... 31
9.4.
Treatment Compliance ........................................................................................... 31
9.5.
Method of Assigning Subjects to Treatment Groups................................................ 31
9.6.
Blinding and Unblinding Treatment Assignment..................................................... 32
9.7.
Permitted and Prohibited Therapies ........................................................................ 32
9.7.1 Permitted Therapies .................................................................................... 33
9.7.2 Prohibited Therapies ................................................................................... 33
9.7.3 Restrictions ................................................................................................ 33
9.8.
Treatment After End of Study ................................................................................ 33
9.9.
Dispensing and Storage .......................................................................................... 34
9.10. Drug Accountability .............................................................................................. 34
9.11. Labeling and Packaging ......................................................................................... 34
9.11.1 Labeling ..................................................................................................... 34
9.11.2 Packaging ................................................................................................... 34
10. STUDY PROCEDURES................................................................................................. 35
10.1. Study Duration ...................................................................................................... 35
10.2. Study Periods and Visits ........................................................................................ 35
10.2.1 Screening and Washout ............................................................................... 35
10.2.1.1 Screening (Visit 1) .......................................................................... 35
10.2.1.2 Washout Period ............................................................................... 36
10.2.2 Baseline (Visit 2) ........................................................................................ 36
10.2.3 Treatment Period (Visits 3, 4, and 5) ........................................................... 37
10.2.4 End of Treatment Period (Visit 6)................................................................ 38
10.2.5 Follow-up (Visit 7) ..................................................................................... 38
10.3. Assessments .......................................................................................................... 39
10.3.1 Efficacy Variables ...................................................................................... 39
10.3.1.1 Hamilton Anxiety Scale................................................................... 39
10.3.1.2 Clinical Global Impression Scales.................................................... 39
10.3.1.3 Patient Global Impression of Change ............................................... 39
10.3.1.4 Adjustment Disorder New Module Scale.......................................... 39
10.3.1.5 International Adjustment Disorder Questionnaire ............................. 40
10.3.2 Safety Variables ......................................................................................... 40
10.3.2.1 Clinical Laboratory Safety Assessments ........................................... 40
10.3.2.2 Clinical Examinations ..................................................................... 42
10.3.2.3 Adverse Events ............................................................................... 42
10.3.2.4 Penn Physician Withdrawal Checklist .............................................. 43
11. ADVERSE EVENTS ...................................................................................................... 44
11.1. Definitions............................................................................................................. 44

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11.1.1 Adverse Events........................................................................................... 44
11.1.2 Unexpected Adverse Events ........................................................................ 44
11.1.3 Serious Adverse Events............................................................................... 44
11.1.4 Significant Adverse Events ......................................................................... 45
11.1.5 Treatment-Emergent Adverse Events........................................................... 45
11.2. Event Assessment and Follow-up of Adverse Events .............................................. 45
11.2.1 Assessment................................................................................................. 46
11.2.2 Evaluation .................................................................................................. 46
11.2.2.1 Severity of Adverse Events.............................................................. 46
11.2.2.2 Seriousness ..................................................................................... 46
11.2.2.3 Actions Taken ................................................................................. 47
11.2.2.4 Outcome at the Time of Last Observation ........................................ 47
11.2.2.5 Adverse Event Relationship to Investigational Product ..................... 47
11.2.3 Documentation ........................................................................................... 47
11.2.4 Treatment of Adverse Events ...................................................................... 48
11.2.5 Follow-up................................................................................................... 48
11.2.6 Reporting ................................................................................................... 48
11.2.6.1 Serious Adverse Events ................................................................... 48
11.2.6.2 Nonserious Adverse Events ............................................................. 49
11.3. Special Considerations ........................................................................................... 50
11.3.1 Pregnancy................................................................................................... 50
11.3.2 Overdose .................................................................................................... 50
12. DATA SAFETY MONITORING BOARD...................................................................... 51
13. STATISTICS.................................................................................................................. 52
13.1. Statistical Analysis................................................................................................. 52
13.1.1 Analysis Populations................................................................................... 52
13.1.1.1 Estimand Framework ...................................................................... 52
13.1.2 Study Subjects and Demographics ............................................................... 53
13.1.2.1 Disposition and Withdrawals ........................................................... 53
13.1.2.2 Protocol Deviations ......................................................................... 54
13.1.2.3 Demographics and Other Baseline Characteristics ............................ 54
13.1.3 Exposure and Compliance ........................................................................... 54
13.1.4 Efficacy Analysis........................................................................................ 54
13.1.4.1 Efficacy Endpoints .......................................................................... 55
13.1.4.2 Primary Analysis............................................................................. 55
13.1.4.3 Secondary Analyses ........................................................................ 55

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13.1.5 Safety and Tolerability Analyses ................................................................. 56
13.1.5.1 Adverse Events ............................................................................... 56
13.1.5.2 Clinical Laboratory Evaluations....................................................... 57
13.1.5.3 Vital Signs ...................................................................................... 57
13.1.5.4 Twelve-lead Electrocardiograms ...................................................... 57
13.1.5.5 Physical Examination Findings ........................................................ 57
13.1.6 Interim Analysis ......................................................................................... 57
13.2. Sample Size Determination .................................................................................... 58
14. STUDY CONDUCT ....................................................................................................... 59
14.1. Sponsor and Investigator Responsibilities ............................................................... 59
14.1.1 Sponsor Responsibilities ............................................................................. 59
14.1.2 Investigator Responsibilities........................................................................ 59
14.1.3 Confidentiality and Privacy ......................................................................... 59
14.2. Site Initiation ......................................................................................................... 60
14.3. Screen Failures ...................................................................................................... 60
14.4. Study Documents................................................................................................... 60
14.4.1 Informed Consent ....................................................................................... 60
14.4.2 Investigator’s Regulatory Documents .......................................................... 61
14.4.3 Case Report Forms ..................................................................................... 61
14.4.4 Source Documents ...................................................................................... 62
14.5. Data Quality Control.............................................................................................. 62
14.5.1 Monitoring Procedures................................................................................ 62
14.5.2 Data Management ....................................................................................... 62
14.5.3 Quality Assurance/Audit ............................................................................. 63
14.6. Study Termination ................................................................................................. 63
14.6.1 Premature Study Termination ...................................................................... 63
14.7. Study Site Closure ................................................................................................. 64
14.7.1 Record Retention ........................................................................................ 64
14.7.2 Sample Retention........................................................................................ 64
14.8. Changes to the Protocol......................................................................................... 64
14.9. Use of Information and Publication ........................................................................ 65
15. FINAL CLINICAL STUDY REPORT ............................................................................ 66
16. ETHICAL AND LEGAL CONSIDERATIONS............................................................... 67
16.1. Good Clinical Practice ........................................................................................... 67
16.2. Subject Information and Informed Consent and/or Assent ....................................... 67
16.3. Approval by Institutional Review Board ................................................................. 67
16.4. Finance and Insurance............................................................................................ 67
17. REFERENCES ............................................................................................................... 68

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18. ATTACHMENTS .......................................................................................................... 72
18.1. Investigator’s Agreement ....................................................................................... 72
APPENDICES ...................................................................................................................... 73
A. 
Hamilton Anxiety Scale ......................................................................................... 74
B. 
Adjustment Disorder New Module Scale ................................................................ 75
C. 
International Adjustment Disorder Questionnaire.................................................... 77
D. 
Penn Physician Withdrawal Checklist..................................................................... 79
E. 
Regulations and Good Clinical Practice Guidelines ................................................. 80
3.1. List of In-Text Tables 
Table 2-1: 
Schedule of Events ..................................................................................... 10
Table 13-1: 
Strategies for Handling Intercurrent Events.................................................. 53
 

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4. LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
ABBREVIATION
EXPLANATION 
ADNM 
Adjustment Disorder New Module Scale 
AE 
adverse event 
AjD
adjustment disorder 
AjDA 
adjustment disorder with anxiety symptoms 
CFR 
Code of Federal Regulations 
CRA 
clinical research associate 
C-SSRS 
Columbia-Suicide Severity Rating Scale  
CGI-I 
Clinical Global Impression – Improvement 
CGI-S 
Clinical Global Impression - Severity Scale 
COVID-19 
coronavirus disease 2019 
ECG 
electrocardiogram 
EDC 
electronic data capture 
DSM-5 
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition 
eCRF 
electronic case report form 
FDA 
Food and Drug Administration 
GCP
Good Clinical Practice
HAM-A 
Hamilton Anxiety Scale
IADQ 
International Adjustment Disorder Questionnaire 
IB  
investigator brochure 
ICE 
intercurrent event 
ICF
informed consent form 
ICH
International Council for Harmonisation 
ID 
identification 
i.n. 
intranasal
IND 
Investigational New Drug 
IP 
investigational product 
IRB 
institutional review board 
ITT
intent-to-treat 
IWRS 
interactive web response system 
LSAS 
Liebowitz Social Anxiety Scale
MADRS 
Montgomery-Asberg Depression Rating Scale 
MINI 
Mini-International Neuropsychiatric Interview
PGI-C 
Patient Global Impression of Change
PWC-20 
Penn Physician Withdrawal Checklist 
PH94B 
PH94B Nasal Spray 
SAD 
social anxiety disorder 

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ABBREVIATION
EXPLANATION 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SIGH-A 
Structured Interview Guide for the HAM-A 
SUDS 
Subjective Units of Distress Scale 
UAE 
unexpected adverse event 

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5. INTRODUCTION 
5.1. Background and Rationale 
5.1.1
Adjustment Disorder 
Adjustment disorder (AjD) refers to a maladaptive emotional and/or behavioral response to an 
identifiable stressor occurring within 3 months of the onset of the stressor as evidenced by one or 
both of the following: (1) marked distress that is out of proportion to the severity or intensity of 
the stressor, taking into account socially or culturally expected reactions; and/or (2) significant 
impairment or interference with a person’s social, occupational or other important areas of daily 
functioning. Unlike post-traumatic stress disorder or acute stress disorder, which have clear criteria 
for what constitutes a traumatic event, adjustment disorder criteria do not specify any requirements 
for what may be regarded as a stressor giving rise to AjD. However, research has identified that 
identifiable stressor events may include both traumatic events, such as exposure to actual or 
threatened death or illness of a loved one, oneself or others (e.g., stress experienced by healthcare 
workers and first responders related to the coronavirus disease 2019 [COVID-19] pandemic),
medical condition, as well as non-traumatic stressful events, such as interpersonal conflict, 
unemployment, and financial difficulties. Importantly the stress reaction can be so great in AjD 
that patients attempt suicide. Indeed, patients diagnosed with AjD have a 12-fold increased rate of 
suicide compared to controls.1 
According to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), 
6 subtypes of AjD feature symptoms of: (i) depressed mood; (ii) anxiety; (iii) mixed anxiety and 
depressed mood; (iv) disturbance of conduct; (v) mixed disturbance of emotions and conduct; and 
(vi) unspecified. Because PH94B has been shown to be safe in all clinical studies to date, to have 
significant clinical efficacy in treating anxiety in subjects with social anxiety disorder (SAD),2,3
and because PH94B’s antidepressant properties are as yet unknown, the present Phase 2a study 
will be focused on adjustment disorder with anxiety (AjDA).4 
Current treatments for AjD include both psychosocial and pharmacological measures. 
Psychosocial treatments include exposure therapy and cognitive behavioral therapy. 
Pharmacological measures vary widely and include antidepressants (selective serotonin reuptake 
inhibitors, and serotonin-norepinephrine reuptake inhibitors), benzodiazepines, buspirone and 
natural products such as cannabidiol.5 Interestingly, the non-benzodiazepine drug etifoxine has 
shown efficacy in AjD.6 This may be relevant to the present study of PH94B because etifoxine is 
known to induce the synthesis of centrally active neurosteroids.7 
5.1.2 Nasal Chemosensory Systems 
In humans, as in other mammals, the olfactory system is a rostral projection of the telencephalon, 
and it is the only sensory system with direct neural access to the limbic system without a relay in 
the thalamus. Therefore, the limbic amygdala is the only brain structure that receives rapid afferent 
neural inputs from peripheral nasal chemosensory receptors.8,9 Chemical cues acting on nasal 
chemosensory neurons trigger sensory inputs that reach the limbic amygdala through a rapid 
(oligosynaptic) neural path. 
The relevance of the olfactory system in behavior is revealed by the serious behavioral impairment 
that occurs after bilateral olfactory bulbectomy in laboratory animals,10,11 and the development of 
anxiety and depression in humans with congenital anosmia.12,13 

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Stimulation of human olfactory chemosensory cells with primary odors produces olfactory 
awareness via the main olfactory neural circuits,14,15 but in humans there are chemosensory cues 
that engage nasal chemosensory receptors and induce behavioral and neuroendocrine responses, 
without olfactory awareness.16-21 These chemosignals induce activation of accessory olfactory 
neural circuits.22-27 Some mammals including humans do not have an accessory olfactory system
and neural impulses arising from nasal chemosensory neurons activated by odorless chemosignals 
trigger subsets of neurons in the main olfactory bulbs which project directly to the cortical and the 
medial amygdala. This in turn triggers an important contingent of forward inhibitory gamma 
aminobutyric acid (GABA)ergic neural circuits in the central amygdala involved in the modulation 
of fear and anxiety.26-31
The olfactory-limbic neural circuits play an important role in social behavior and 
emotions.16-18,24,32,33 This has been confirmed in molecular biology/behavioral studies, in studies 
using knockout mouse lines with loss of function in different zones of the olfactory bulbs,25 in 
human functional magnetic resonance imaging studies,17,34 in clinical studies in human subjects 
with isolated congenital anosmia,12,35 and in subjects with congenital hypogonadotropic 
hypogonadism,36 and in clinical studies in patients with anxiety and depression.21,37 
Pherines are a family of synthetic neuroactive steroid molecules that engage specifically with 
human nasal chemosensory receptors. Pherines stimulate receptor neurons in the human nasal 
chemosensory epithelium19,38-40 that activate olfactory bulb neurons and in turn trigger neural 
circuits in the limbic amygdala. This leads to activation of the anterior gyrus, hypothalamus, 
hippocampus and prefrontal cortex, and it is different from the brain areas activated by primary 
olfactory stimuli.17-34 Pherines are odorless, and brain activation by pherines does not produce 
olfactory awareness17,19 and can modulate brain autonomic and psychophysiological 
responses.2,16,18,20,34,41,42 
5.1.3 PH94B 
PH94B (3 -androsta-4,16-dien-3-ol) is a synthetic neuroactive steroid that targets human nasal 
chemosensory receptor cells16,40 and has been demonstrated in Phase 2 clinical trials to have 
benefits for the acute treatment of anxiety in subjects with SAD.3 
Pherines induce calcium ion entry in human nasal chemosensory neurons.41,42 Pherines such as 
PH94B target G-protein-coupled receptors that are expressed in human nasal chemosensory 
neurons.38-44 
In vitro screening studies using isolated, living, human nasal chemosensory neurons have shown 
that picomolar quantities of PH94B can selectively induce inward currents in a concentration-
dependent and reversible fashion.45 These membrane currents are carried by calcium ions.42 In 
institutional review board (IRB)-approved studies, pulsatile intranasal (i.n.) administration of 
nanogram quantities of airborne PH94B to human subjects induced dose-dependent depolarization 
of the electrogram recorded from the surface of the nasal chemosensory epithelium, which is a 
measure of the local mass receptor potential response. 
 
 
 PH94B exerts its activity by stimulation of neural circuits involving the limbic 
amygdala, and it does not require systemic uptake and distribution to produce its anxiolytic 
pharmacological effects. PH94B is being investigated as a potential acute treatment for the 

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alleviation of anxiety symptoms in adult patients with SAD. While PH94B may regulate gamma 
aminobutyric acid circuits in the limbic amygdala, electrophysiological experiments in vitro show 
that PH94B does not directly bind to or modulate gamma aminobutyric acid receptors at 
concentration 10 µM or lower, which differentiates its mechanism of action from that of 
benzodiazepines.46 
5.2. Clinical Experience 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5.2.1 Phase 1 Studies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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5.2.2 Phase 2 Studies 
For SAD, 2 double-blind, randomized, placebo-controlled Phase 2 clinical studies (PH94B-CL016 
and -CL022) included a total of 91 female subjects who met criteria for SAD (generalized subtype) 
as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. PH94B 
(1.6 µg) was administered i.n.
to both a performance (public speaking) challenge 
and a social interaction challenge simulation which took place at the clinical sites.
 
 The primary outcome measures were the Clinical 
Global Impression Scale - Improvement (CGI-I) and the Subjective Units of Distress Scale 
(SUDS). SUDS scores range from zero to 100, with higher scores indicating greater levels of 
anxiety. Subjects receiving PH94B were more likely than those who received placebo to show 
improvement on the CGI-I following treatment. In the PH94B group, 34 of 45 subjects (75.6%) 
were rated very much improved or much improved compared to only 17 of 46 subjects (37%) in 
the placebo group. A test for the difference between proportions indicated a Z value of 4.03, 
p = 0.0001 (Fisher’s exact test). 
During the public speaking challenge, subjects randomized to PH94B (n = 45) showed an 
improvement of 26.7 points in the mean SUDS score at Visit 3 (initial treatment visit) as compared 
to Visit 2 (Baseline, at which all subjects received placebo). In comparison, subjects randomized 
to placebo (n = 46) showed an improvement of only 14.0 points in the mean SUDS score across 
visits. The PH94B group’s improvement from Visit 2 to Visit 3 significantly exceeded the placebo 
group’s improvement from Visit 2 to Visit 3 (t = 3.16, p = 0.002) on this challenge. No SAEs were 
reported, and no subjects were terminated prematurely from the study due to AEs. 
5.3. Summary of Potential Risks and Benefits 
The potential benefits of study participation are that subjects with AjDA may experience a 
reduction in their symptoms when they encounter anxiety-provoking situations in daily life as a 
result of treatment with PH94B. No other benefits of participation are anticipated. 
Based on previous clinical studies conducted with PH94B, it is believed to be safe and well 
tolerated, and risks to subjects are considered minimal. Intranasal administration of PH94B may 
increase the risk of local site reactions including itching, burning, runny nose, sneezing and 
soreness inside the nose. In completed clinical studies, the most commonly reported AE was 
headache. None of these effects was reported in more subjects receiving PH94B than in subjects 
receiving placebo. In a nonclinical long-term safety study, no toxic effects were observed in rats 
administered repeated daily doses of PH94B for 6 months, suggesting that prolonged exposure to 
PH94B is safe; no toxic effects are expected with prolonged exposure in humans. 
A summary of the pharmaceutical properties and known potential risks of PH94B is provided in 
the current version of the investigator brochure (IB). The Investigator must become familiar with 
all sections of the PH94B IB before the start of the study. 

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7. STUDY DESIGN 
7.1. Overall Study Design and Plan 
The study is a Phase 2a, double-blind, placebo-controlled, parallel study of i.n. PH94B versus 
placebo in 40 adult subjects with AjDA as defined by the DSM-5.
Subject participation in the study will last a total of 6 to 10 weeks, depending on the duration of 
the screening period and intervals between visits. Upon signing an informed consent, all subjects 
will complete Visit 1 (Screening) and enter a screening period lasting 7 to 35 days and includes a 
taper of concomitant anxiolytics, if necessary. As this protocol requires patients to be free of 
benzodiazepine anxiolytics for 30 days prior to baseline, the maximum screening period accounts 
for both a taper period and a 30 day benzodiazepine-free period if needed. The Screening visit will 
consist of safety assessments and psychiatric assessments to determine eligibility. After the 
screening period, eligible subjects will then return to complete Visit 2 (Baseline). If the subject 
continues to meet inclusion and exclusion criteria after review of psychiatric scales and laboratory 
results, the subject will be randomized 1:1 to receive 4 weeks of either PH94B or placebo 
administered 4 times daily. The subject will be trained on using the investigational product (IP) 
and it will be dispensed in 2 vials. 
Subjects will return for weekly site visits (Visits 3, 4, and 5), in which the subject will return the 
IP vials dispensed at the previous visit and receive 2 new vials. Concomitant medications and AEs 
will be recorded. During these visits, the Hamilton Anxiety Scale (HAM-A), Patient Global 
Impression of Change (PGI-C), CGI-I Scale, Clinical Global Impression - Severity (CGI-S), and 
Columbia-Suicide Severity Rating Scale (C-SSRS) will be completed. Vital signs will be 
collected, and nasal passages will be examined. 
When the subject returns for Visit 6, besides the assessments completed at Visits 3 through 5, the 
subjects will complete the Adjustment Disorder New Module Scale (ADNM), International 
Adjustment Disorder Questionnaire (IADQ), and Montgomery-Asberg Depression Rating Scale 
(MADRS) and have a physical examination, electrocardiogram (ECG), laboratory tests (chemistry 
and blood), urinalysis, urine drug screen, and urine pregnancy test. Any remaining IP vials will be 
collected. The subject will then come back after a 1-week washout period for the Follow-up visit 
(Visit 7). The HAM-A, C-SSRS, and the 20-item Physician Withdrawal Checklist (PWC-20) will 
be completed and any changes in AEs and concomitant medications from the last visit will be 
collected. 
For each visit following Baseline (Visit 2), a ±2-day window will be allowed. 
7.2. Rationale and Discussion of Study Design 
The present study employs a randomized, double-blind, placebo-controlled, parallel design, which 
is generally considered to be the gold-standard for clinical trials. The use of a placebo for the study 
comparator is based on the absence of an active comparator that could be delivered by the 
i.n. route, which is essential for maintaining the study blind. 
Subjects will complete the HAM-A, an established scale, to rate their anxiety. Additional 
evaluations include the PGI-C, ADNM (a newer scale validated for classification of severity of 
AjDA), and the IADQ (a recently validated questionnaire to identify stressful events subjects have 
experienced, as well as their potential social impact). Objective evaluations, performed by the 
Investigator and a trained observer, include the CGI-I and CGI-S. 

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Safety assessments are standard for the evaluation of an investigational medicinal product, and 
include collection of AEs and SAEs, and evaluation of vital signs, safety laboratory tests, ECGs, 
and physical examinations; given the use of the i.n. route of administration, the physical 
examination will include an examination of the nasal passages. Given that subjects are patients 
with a confirmed diagnosis of AjDA, the C-SSRS will be used at each study visit as a precautionary 
measure. 
7.3. Selection of Doses in the Study 
The i.n. route of administration is required for the small quantities of PH94B to engage directly 
with nasal chemosensory neurons interspersed in the nasal olfactory epithelium.
Nonclinical and clinical studies with PH94B are summarized in the IB. Nonclinical and clinical 
data have shown that PH94B is safe for use in human subjects at increasing doses up to
 
PH94B could not be quantified in blood samples of human subjects administered 
 i.n. in a 
Phase 1 trial. No SAEs associated with the administration of PH94B have been observed in any 
clinical study to date. To date, the safety margin-based No-Observed-Adverse-effect level from 
toxicity levels have indicated that the proposed doses are safe. The profile of physiological and 
behavioral responses to PH94B was similar for males and females, but the magnitude of effect is 
slightly reduced for males at the 1.6 µg dose. This study proposes that
 of PH94B or placebo 
, be self-administered i.n. by the subjects 4 times per day, separated 
by at least 2 hours (target morning, noon, early evening, and bedtime). This is based on Phase 1 
and Phase 2 study outcomes in general, and in particular on the observations made in study 
PH94B-CL019. Subjects will be randomly assigned to treatment with either PH94B or placebo. 
7.4. Study Sites 
It is projected that up to 2 centers will participate. 
7.5. End of Study Definition 
A clinical trial is considered completed when the last subject’s last study visit has occurred. 

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8. SUBJECT POPULATION 
8.1. Selection of Study Population 
Eligibility for participation in the study will be determined from demographic information, medical 
and psychiatric history, physical and psychiatric examination, ECG, clinical laboratory findings, 
and clinical rating scale assessments performed at the Screening (Visit 1) and Baseline (Visit 2). 
Subjects may be recruited from the Investigator or sub-Investigator clinical practices, the center’s 
existing database, referring physicians, or direct advertisement or other lead generation source. 
Any information to be disseminated to potential subjects (handouts, brochures, etc.), as well as 
direct advertisements, including direct electronic or digital advertising, must be approved by 
VistaGen Therapeutics, Inc. and by the central IRB prior to use and implementation. 
8.2. Study Entry Criteria 
Subjects who do not meet all of the eligibility criteria will not be enrolled. 
8.2.1
Inclusion Criteria 
To be considered eligible to participate in the study, a subject must meet the inclusion criteria 
listed below: 
1. Written informed consent provided prior to conducting any study-specific assessment. 
2. Male and female adults, 18 years of age. 
3. Current diagnosis of AjDA as defined in the DSM-5. 
4. Clinician-rated HAM-
at Baseline (Visit 2). 
5. Clinician-rated MADRS total score <20 at Screening (Visit 1) and Baseline (Visit 2). 
6. Clinical Global Impression - 
(Visit 2). 
7. Women of childbearing potential must be able to commit to the consistent and correct use 
of an effective method of birth control throughout the study and must also have a negative 
urine pregnancy test result at both Screening (Visit 1) and Baseline (Visit 2), prior to IP 
administration. Effective methods of contraception include condoms with spermicide, 
diaphragm with spermicide, hormonal contraceptive agents (oral, transdermal, or 
injectable), or implantable contraceptive devices. 
8. Males whose sexual partners are women of childbearing potential must commit to the 
consistent and correct use of an effective method of birth control throughout the study. 
9. Negative COVID-19 test for subjects with COVID-19 symptoms or who have had direct 
exposure to someone with a positive COVID-19 test, as determined by the Investigator. 
8.2.2 Exclusion Criteria 
To be considered eligible for entry into the study, a subject must not meet any of the following 
exclusion criteria: 
1. Any history of schizophrenia or schizoaffective disorder. 

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2. Any other current Axis I disorder, including, but not limited to, major depressive disorder, 
bipolar disorder, post-traumatic stress disorder, obsessive-compulsive disorder, 
premenstrual dysphoric disorder, and generalized anxiety disorder, which is in poor control 
and the primary focus of treatment. 
3. A diagnosis of SAD. 
4. A score >60 on the Liebowitz Social Anxiety Scale (LSAS). 
5. Subjects who meet criteria for moderate or severe alcohol or substance use disorder within 
1 year prior to study entry. 
6. In the opinion of the Investigator, the subject has a significant risk for suicidal behavior 
during their participation in the study, or 
a. At Screening (Visit 1): the subject scores “yes” on items 4 or 5 in the Suicidal 
Ideation section of the C-SSRS with reference to a 6-month period prior to 
screening; or 
b. At Screening (Visit 1): the subject has had one or more suicidal attempts with 
reference to a 2 year period prior to screening; or 
c. At Baseline (Visit 2): the subject scores “yes” on items 4 or 5 in the Suicidal 
Ideation section of the C-SSRS with reference to screening; or 
d. The subject is considered to be an imminent danger to themselves or others. 
7. Clinically significant nasal pathology or history of significant nasal trauma, nasal surgery, 
total anosmia, or nasal septum perforation that may have damaged the nasal chemosensory 
epithelium. 
8. An acute or chronic condition, including an infectious illness, uncontrolled seasonal 
allergies at the time of the study, or significant nasal congestion that potentially could affect 
drug delivery to the nasal chemosensory epithelium. The Investigator may allow 
concomitant use of over-the-counter nasal decongestants as needed, since there is no 
apparent drug interaction between these and PH94B. 
9. Concomitant use of any anxiolytics, such as benzodiazepines, buspirone, or cannabinoids 
during the study and within 30 days of Baseline (Visit 2). 
10. Concomitant use of any over-the-counter, prescription product, or herbal preparation for 
treatment of the symptoms of anxiety during the study and within 30 days before study 
entry. Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake 
inhibitors, or other approved antidepressants are permitted if the dose has been stable for 
30 days prior to Baseline (Visit 2). 
11. Women who have a positive urine pregnancy test prior to IP administration or are currently 
breast feeding. 
12. Subjects with clinically significant abnormalities in hematology, blood chemistry, 
urinalysis, electrocardiogram, or physical examination identified at Screening (Visit 1) that 
in the clinical judgment of the Investigator, could place the subject at undue risk, interfere 
with study participation, or confound the results of the study. 
13. Subjects with a positive urine drug screen at either Screening (Visit 1) or Baseline (Visit 2). 

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14. Any current clinically significant and/or uncontrolled medical condition, based on medical 
history or as evidenced in screening assessments, such as COVID 19, HIV, cancer, stroke, 
congestive heart failure, uncontrolled diabetes mellitus, or any other medical condition or 
disease that, in the clinical judgment of the Investigator, could place the subject at undue 
risk, interfere with study participation, or confound the results of the study. 
15. Use of a concomitant medication that, in the clinical judgment of the Investigator, could 
place the subject at undue risk, interfere with study participation, or confound the results 
of the study. 
16. History of cancer or malignant tumor not in remission for at least 2 years. Basal cell skin 
cancers are not exclusionary. 
8.3. Premature Subject Withdrawal 
All subjects will be advised that they are free to withdraw from participation in this study at any 
time, for any reason, and without prejudice. The Investigator should make every reasonable 
attempt to complete all of the scheduled weekly assessments; with the exception of subjects who 
withdraw consent to participate in the study. Investigators must attempt to contact subjects who 
fail to attend scheduled visits by telephone or other means to exclude the possibility of an AE being 
the cause of withdrawal. Should this be the cause, the AE must be documented, reported, and 
followed as described in Section 11.2. 
The sponsor reserves the right to request the withdrawal of a subject due to protocol deviations or 
other reasons. 
The Investigator also has the right to withdraw subjects from the study at any time for the following 
reasons: 
 Any AE, laboratory abnormality, or concomitant illness which, in the opinion of the 
Investigator, indicates that continued treatment with IP or any other aspect of the study is 
not in the best interest of the subject 
 Disease progression that, in the Investigator’s opinion, precludes the subject’s continued 
participation in the study 
 Significant non-compliance with the requirements of the protocol or treatment 
 The subject misses 2 consecutive scheduled visits during the 4-week treatment period 
 The subject is unable to tolerate study medication based on the Investigator’s judgment 
 Subject requires PH94B administration more than 4 times per day 
 The subject requires a medication prohibited by the protocol (Section 9.7.2) 
 Termination of the study by VistaGen Therapeutics, Inc. 
 At the discretion of the Investigator or VistaGen Therapeutics, Inc. 
If a subject is withdrawn before completing the study, the reason for withdrawal and the date of 
discontinuation will be recorded on the appropriate page of the electronic case report form (eCRF). 
Whenever possible and reasonable, the evaluations that were to be conducted at the completion of 
the study should be performed at the time of premature discontinuation. 

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Subjects who discontinue early from the study will be asked to return for originally scheduled 
weekly assessments. If this is not possible, all attempts will be made to have subjects return to the 
study center to complete the assessments listed for Visit 6 (see Section 10.2.4) as soon as possible. 
All attempts, including phone or email, to contact the subject must be recorded in the source 
documents. If the subject fails to respond to those methods, a certified, return receipt letter must 
be sent to the subject’s address indicating that they should contact the study center, with a copy 
retained in the source documents. Only if all of these attempts fail will it be deemed that the subject 
is in fact Lost to Follow-up and no final safety data can be collected. No tapering of IP is required 
in the event of early withdrawal. 
Subjects who sign the informed consent form (ICF) and are subsequently withdrawn will not be 
replaced. 
8.4. Subject Replacement Criteria 
Withdrawn subjects will not be replaced. If a substantial number of subjects are withdrawn from 
the study, the sponsor will evaluate the need for developing replacement criteria. 
Randomized subjects who are withdrawn from the study may not re-enter. The subject number for 
a withdrawn subject will not be reassigned to another subject. 

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9. TREATMENTS
All IP should 
at the site
 
 The first dose will be administered at the study site. 
Site personnel will instruct the subject to prime, then self-administer the IP by 
 
 
 
9.1. Identification of Investigational Product 
The IP is defined as the spray delivery device containing PH94B or placebo. 
PH94B 
 
 
The placebo is odorless and contains the identical excipients without PH94B. 
PH94B and placebo are similar in appearance. 
PH94B and placebo will be supplied
 
  
The spray delivery device consists of an actuator and a 10-mL amber glass vial which contains 
8 mL of IP. 
Use of the i.n. route is essential given the site of action of PH94B on nasal sensory chemoreceptors 
(see Section 5.1). 
PH94B and placebo will be supplied by 
 
 
  
9.2. Selection of Timing of Dose for Each Subject 
Before initiation of treatment with the IP at Baseline (Visit 2), subjects will be trained by the 
Investigator or delegated staff in the proper technique for priming and self-administration of IP as 
outlined in the Study Manual. 
The IP is to be delivered i.n. with the nozzle of the applicator positioned in the nasal vestibule and 
directed toward the midline (lower anterior part or nasal septum). To administer study medication, 
the actuator (pusher) should be depressed completely. 
Prior to the use of a new IP vial, subjects will prime the spray pump by depressing the actuator 
4 times. 
 After 
the new IP vial has been primed for the first administration, only one priming spray is required for 
subsequent doses. 
Subjects will be instructed to administer
 
 The administration will be 
done during waking hours and the suggested spacing is at morning, noon, early evening, and 
bedtime. 
 
 Placebo IP is one 100 µL spray per nostril for a total 

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of 200 µL. Study drug will be self-administered 4 times a day. The spacing between doses needs 
to be at least 2 hours. 
9.3. Dose Adjustment Criteria 
Dose adjustment is not allowed in this study. 
9.4. Treatment Compliance 
At Visits 2, 3, 4 and 5; subjects will be dispensed 2 vials of the appropriate IP. Subjects will take 
home the vials and store and use the IP at room temperature. 
Before dispensing the vial(s) to a subject, the Investigator or study site staff will proceed as 
follows: (a) identify/mark the 2 vials as vial #1 and vial #2, (b) weigh the vials and record, 
registering the vial number and weight in the source document, c) instruct the subject to prime 
(4 sprays) the initial (#1) spray vial, and (d) have the subject self-administer the initial IP dose in 
the clinic office. 
In the event a subject loses a vial of IP and requires a replacement vial to be dispensed, the 
Investigator or study coordinator must contact VistaGen Therapeutics, Inc. or its designee for 
replacement instructions. Study site staff will not be allowed to deviate from the dispensation order 
listed above for any reason. 
The Investigator or study site staff will instruct the subject to return the used spray vials during the 
following visit to the clinic. At that time, the study personnel will weigh the returned vials and 
record the vial numbers and weights in the source document for compliance check. 
Current and accurate inventory and dispensing records will be kept for all IP, and upon study 
completion, a final inventory of all clinical supplies will be compiled. All IP containers, whether 
empty or containing unused IP, will be returned per the sponsor’s instructions from the clinical 
monitor. A copy of the Drug Receipt Form and the Drug Accountability Form will be retained in 
the Investigator’s files. 
Compliance with dosing instructions will be reasonably ascertained by weighing the vials as 
detailed in the Study Manual. The weight of the returned vials will be recorded in the source 
documents. Additional instructions will be provided in the Study Manual, including the estimated 
compliance calculation. 
In the event the subject fails to return the IP vial(s) that was dispensed at the prior visit, site staff 
should ask the subject to return the vials to the site as soon as possible, preferably within 24 hours, 
but at the very least at the next scheduled study visit. The Investigator will also explicitly and 
thoroughly instruct the subject not to administer any further doses from the previously dispensed 
vial. 
9.5. Method of Assigning Subjects to Treatment Groups 
In this parallel group, randomized study, subjects who meet study entry criteria will be randomly 
assigned in a 1:1 ratio to PH94B or placebo. The randomization schedule will be computer 
generated using a permuted block algorithm and will randomly allocate IP to randomization 
numbers. The randomization numbers will be assigned sequentially through a central interactive 
web response system (IWRS) as subjects are entered into the study. The randomization schedule 
will be stratified by site. Study center will not be a blocking factor in the randomization schedule. 

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The randomization schedule will be prepared by Premier Research before the start of the study. 
No one involved in the study performance will have access to the randomization schedule before 
official unblinding of treatment assignment. No subject will be randomized into this study more 
than once. 
9.6. Blinding and Unblinding Treatment Assignment 
All subjects, investigators, and study personnel involved in the conduct of the study, including 
data management, will be blinded to treatment assignment with the exception of a specified 
unblinded statistician and a member of the Interactive Response Technology team from Premier 
Research who will have access to the randomization code. The unblinded study personnel will not 
participate in study procedures or data analysis prior to unblinding of the study data to all 
study-related personnel. If an interim analysis is to be conducted, then unblinded personnel who 
are not otherwise involved in the study will prepare the data for review.
Study personnel will make every effort to safeguard the integrity of the study blind to minimize 
bias in the conduct of the study. Treatment unblinding is discouraged if knowledge of the treatment 
assignment will not materially change the planned management of a medical emergency. 
Unblinding will be permitted in a medical emergency that requires immediate knowledge of the
subject’s treatment assignment. All IP containers will be provided with a code that will unblind 
the contents in an emergency (details are provided in the Study Manual). 
Unblinding should be discussed in advance with the Medical Monitor, if possible. For emergency 
unblinding, study personnel will use the IWRS. If the Investigator is not able to discuss treatment 
unblinding in advance, then he/she must notify the Medical Monitor as soon as possible about the 
unblinding incident without revealing the subject’s treatment assignment. 
The Investigator or designee must record the date and reason for treatment unblinding on the 
appropriate eCRF for that subject. In all cases that are not emergencies, the Investigator must 
discuss the event with the Medical Monitor prior to unblinding the subject’s treatment assignment. 
If treatment assignment is unblinded for an individual subject, study personnel will be notified of 
that subject’s treatment assignment without unblinding the treatment assignments for the 
remaining subjects in the study. Thus, the overall study blind will not be compromised. If a 
subject’s treatment assignment is unblinded, he/she may or may not be asked to withdraw from 
the study. The Investigator will make this decision after consultation with the Medical Monitor. 
Overall unblinding will take place at the end of the study only after database lock has been 
achieved. 
9.7. Permitted and Prohibited Therapies 
All concomitant medications used (including over-the-counter medications and herbal 
supplements) will be recorded in the source document and on the appropriate eCRF. 
All medications taken by or administered to the subject during the month prior to Screening 
(Visit 1) should be recorded in the eCRF. With the exception of those noted in Section 8.2.2, all 
medications (prescription or over-the-counter) that were started prior to Screening (Visit 1) may 
be continued during the course of the trial. During the study, subjects should stay on stable doses 
of their usual allowable medication regimens. Medications for treatment of minor concurrent 
illnesses unrelated to AjDA that arise after Screening (Visit 1) may be allowed at the discretion of 
the Investigator, except for the prohibited therapies specified in the protocol. 

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To ensure that appropriate concomitant therapy is administered, it is essential that subjects be 
instructed not to take any medication (either self-administered non-prescription drugs or 
prescription therapy prescribed by another physician) without prior consultation with the 
Investigator. The Investigator should consider the acceptability of all concomitant medications not 
explicitly prohibited. Sites should contact the Medical Monitor when uncertain about the 
acceptability of concomitant medications. All concomitant medication taken during the study will 
be recorded on appropriate pages of the eCRF. 
9.7.1 Permitted Therapies 
With the exception of those noted in Section 9.7.2, all medications (prescription or over-the-
counter) that were started prior to Screening (Visit 1) may be continued during the course of the 
trial. During the course of the study, subjects should stay on stable doses of their usual allowable 
medication regimens. Medications for treatment of minor concurrent illnesses that arise after 
Screening (Visit 1) may be allowed at the discretion of the Investigator, with the exception of the 
prohibited therapies specified in Section 9.7.2. 
The use of eszopiclone, ramelteon, melatonin, zaleplon, zolpidem, low-dose doxepin or 
anti-histamines for the treatment of insomnia is permitted. 
PH94B has no apparent pharmacodynamic drug interaction with phenylephrine and oxymetazoline 
in vitro. Investigator may allow concomitant use of over-the-counter nasal decongestants as 
needed. If the subject is taking nasal formulations, they should be spaced 15 minutes from IP 
administration. 
9.7.2 Prohibited Therapies 
With the exception of concomitant medications for the treatment of insomnia described in 
Section 9.7.1, no other psychotropic medication besides IP is permitted to be used by any subject 
between Screening (Visit 1) and Follow-up (Visit 7). Prohibited psychotropic medications include 
centrally acting medications used to treat pain and muscle spasms, such as gabapentin and 
cyclobenzaprine. 
Prior use of PH94B is not permitted. 
Where washout of prohibited medications is required before randomization, tapering rates are at 
the discretion of the Investigator and are to be determined on an individual basis, with 
consideration to subject state, dose, and known pharmacokinetics of the medication being 
discontinued. The subject must be consented before any tapering is started. If the washout of the 
anti-anxiety medications makes the subject clinically unstable, the Investigator has the discretion 
to not to proceed with the subject in the study. 
9.7.3 Restrictions 
Subjects who meet criteria for moderate or severe alcohol or substance use disorder (including 
cannabinoids) within the 1 year prior to study entry will be excluded from the study. 
9.8. Treatment After End of Study 
After the end of the study, each subject will be treated according to standard clinical practice. 

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9.9. Dispensing and Storage 
The test product supplied by 
 is to be used exclusively in the clinical study 
according to the instructions of this protocol. The Investigator is responsible for dispensing the IP 
according to the dosage scheme and for ensuring proper storage of the IP. 
The Investigator must confirm the receipt of the IP with his or her signature. A copy of this receipt 
must be kept by the Investigator and another copy will be stored at VistaGen Therapeutics, Inc. 
and at Premier Research. 
All IP supplied to each site by the sponsor will be maintained in a safe and secure (locked) area, 
stored 
 until dispensed, and
 
 Access should be restricted to the designated responsible member/s 
of the Investigator’s staff and to the clinical monitor. The Investigator agrees that neither he/she 
nor any of the study staff will supply IP to any person other than subjects enrolled in the study. 
The key to the storage area is to be kept by the Investigator or designee responsible for the IP. The 
store will be accessible only to those persons authorized by the Investigator to dispense the IP. 
9.10. Drug Accountability 
Upon receipt of each IP shipment, an inventory must be performed, and a drug receipt log filled 
out and signed by the person accepting the shipment. It is important that the designated study staff 
counts and verifies that the shipment contains all the items noted in the shipment inventory. Any 
damaged or unusable IP in a given shipment (active drug or comparator) must be documented in 
the study files and reported immediately to the monitor. 
9.11. Labeling and Packaging 
Labeling and packaging of the IPs will be performed by
 
 
9.11.1 Labeling 
The vials will have a label affixed that meets the applicable regulatory requirements and may 
include the following: subject identifier, IP name, dosage strength, lot number, protocol number, 
specified volume of contents, caution statement (“New Drug – Limited by United States Law to 
Investigational Use” and “Keep out of reach of children”), storage, and sponsor identification. 
Investigators must save all empty packaging or packaging containing used and unused vials for 
final disposition by the sponsor or contract pharmacy. 
9.11.2 Packaging 
IP will be supplied in amber glass vials. The spray delivery device consists of an actuator and a 
10-mL amber glass vial. 

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10. STUDY PROCEDURES 
Subjects must provide written informed consent before any study-related procedures are initiated, 
including the cessation and taper of prohibited concomitant therapy.
For the timing of assessments and procedures throughout the study, refer to the schedule of events 
(Table 2-1). Throughout the study, every reasonable effort should be made by study personnel to 
follow the timing of assessments and procedures in the schedule of events for each subject. If a 
subject misses a study visit for any reason, the visit should be rescheduled as soon as possible. The 
same trained rater should complete the appropriate assessment with the subject for all visits. 
10.1. Study Duration 
The study comprises a screening period of up to 35 days, a double-blind phase of 4 weeks, followed 
by a follow-up visit approximately 1 week later. 
10.2. Study Periods and Visits 
10.2.1 Screening and Washout 
10.2.1.1 Screening (Visit 1) 
Screening begins after the written informed consent has been obtained from the subject. The 
purpose of the screening phase is to: 
 Ensure that appropriate subjects are entered into the trial 
 Determine that the subject meets all eligibility criteria 
 Collect demographic and medical data permitting characterization of the subject 
 Ensure that prohibited medications are discontinued 
To meet these objectives, the duration of screening can be up to 35 days if taper of prohibited 
medication is required. Subjects continuing to meet all eligibility requirements at Baseline (Visit 2) 
will be randomized and dispensed double-blinded IP. 
All subjects agreeing to participate must give written informed consent using the IRB-approved 
ICF before any study-related procedures are performed (including tapering of prohibited 
medications). The ICF will be signed and dated by the subject and Investigator or other appropriate 
site staff, and a copy of the signed ICF will be given to the subject. The informed consent process 
will be documented in the source records for each subject. 
After the ICF process is complete, a subject number will be allocated by the site, by assigning the 
next sequential subject number available.  
The following procedures will be performed at Screening (Visit 1), which is to occur at least 
7 days, but no more than 35 days prior to Baseline (Visit 2): 
 Obtain informed consent 
 Collect demographic information 
 Assign subject number, as described above 

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 Obtain medical history (including nicotine, alcohol and cannabis use, and menstrual 
information on women of childbearing potential) and psychiatric history 
 Record prior and concomitant treatment and medication use (medication name, dose, and 
frequency) 
 Administer MINI 7.0.2 
 Perform physical examination, including height (inches), body weight (pounds), body 
temperature (°F), and clinical examination of both nasal passages 
 Measure vital signs after the subject has rested for 5 minutes: seated systolic and diastolic 
blood pressure, heart rate, respiratory rate, and body temperature 
 Obtain 12-lead ECG 
 Obtain blood and urine samples for clinical laboratory examination, including hematology, 
chemistry, prolactin, thyroid functioning, and urinalysis (refer to Section 10.3.2.1.1 for 
complete list) 
 Obtain urine sample for urine drug screen: Instant Exam to be performed on site, with 
results thoroughly documented in the source 
 For females of childbearing potential, obtain urine sample and complete on-site urine 
pregnancy test. If positive, a serum pregnancy test should be conducted 
 Administer LSAS 
 Administer MADRS 
 Administer HAM-A 
 Administer C-SSRS 
 Administer CGI-S 
 Review all inclusion and exclusion criteria 
10.2.1.2 Washout Period 
Subjects requiring washout of prohibited concomitant medications such as benzodiazepines must 
have stopped taking these medications 30 days prior to Baseline (Visit 2). Selective serotonin 
reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other antidepressants are 
allowed so long as the dose has been stable for 30 days prior to Baseline (Visit 2). 
Refer to Section 9.7.2 for more information concerning washout procedures. 
10.2.2 Baseline (Visit 2) 
For subjects continuing to meet all eligibility criteria, the following assessments will be completed 
at Baseline (Visit 2): 
 Subject to fill out ADNM 
 Administer MADRS 
 Administer HAM-A 

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 Administer C-SSRS (since last visit) 
 Administer CGI-S 
 Administer IADQ 
 Measure vital signs after the subject has rested for 5 minutes: seated systolic and diastolic 
blood pressure, heart rate, respiratory rate, and body temperature 
 Obtain blood and urine samples for clinical laboratory examination, including hematology, 
chemistry, prolactin, thyroid functioning, and urinalysis (refer to Section 10.3.2.1.1 for 
complete list) 
 Obtain urine sample for urine drug screen: Instant Exam to be performed on site, with 
results thoroughly documented in the source 
 For females of childbearing potential, obtain urine sample and complete on-site urine 
pregnancy test 
 Record concomitant medication use including the completion of any washout 
 Review all inclusion and exclusion criteria 
For subjects meeting all study inclusion criteria and no study exclusion criteria, (after review of 
the assessments above) the following Visit 2 procedures will be performed: 
 Randomize the subject and obtain first IP vial 
 Train subjects on use of IP and dosing 
 Prior to giving a vial(s) to the subject, site staff will identify/mark the vials as vial #1 and 
vial #2. Staff will then instruct the subject on initial priming and ongoing priming, as 
outlined in the Study Manual 
 Both IP vials will be weighed (as per instructions in the Study Manual). The subject will 
then complete the initial priming and self-administer the first dose in the presence of site 
personnel 
 Record any AEs reported after IP administration 
The next visit (Visit 3) will be scheduled 1 week (±2 days) after the date of Baseline (Visit 2). 
10.2.3 Treatment Period (Visits 3, 4, and 5) 
At Visits 3, 4, and 5 the following assessments will be completed: 
 Measure vital signs after the subject has rested for 5 minutes: seated systolic and diastolic 
blood pressure, heart rate, respiratory rate, and body temperature 
 Perform clinical examination of both nasal passages 
 Administer HAM-A 
 Administer C-SSRS (since last visit) 
 Administer CGI-S 
 Administer CGI-I 

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 Administer PGI-C 
 Returned vials dispensed at the previous visit and new vials will be weighed and dispensed 
(all weights will be documented in source documents and the eCRF) 
 Record concomitant medication use 
 Review and record AEs 
10.2.4 End of Treatment Period (Visit 6) 
At Visit 6, subjects should return to the site with IP vials dispensed at Visit 5. The following 
assessments will be completed: 
 Subject to fill out ADNM 
 Administer MADRS 
 Administer HAM-A 
 Administer IADQ 
 Administer C-SSRS (since last visit) 
 Administer CGI-S and CGI-I 
 Administer PGI-C 
 Measure vital signs after the subject has rested for 5 minutes: seated systolic and diastolic 
blood pressure, heart rate, respiratory rate, body temperature, and ECG 
 Perform clinical examination of both nasal passages 
 Obtain blood and urine samples for clinical laboratory examination, including hematology, 
chemistry, prolactin, thyroid functioning, and urinalysis (refer to Section 10.3.2.1.1 for 
complete list) 
 Obtain urine sample for urine drug screen: Instant Exam to be performed on site, with 
results thoroughly documented in the source 
For females of childbearing potential, obtain urine sample and complete on-site urine 
pregnancy test 
 Record concomitant medication use 
 Review and record AEs 
10.2.5 Follow-up (Visit 7) 
At Visit 7, the following assessments will be completed: 
 Administer HAM-A 
 Administer C-SSRS (since last visit) 
 Administer PWC-20 
 Measure vital signs after the subject has rested for 5 minutes: seated systolic and diastolic 
blood pressure, heart rate, respiratory rate, body temperature, and ECG 

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 Record concomitant medication use 
 Review and record AEs 
10.3. Assessments 
10.3.1 Efficacy Variables
10.3.1.1 Hamilton Anxiety Scale 
HAM-A is an established scale to measure the severity of a patient’s anxiety. It consists of 
14 questions rated on a 5-point scale (0 = not present to 5 = severe). It is completed by trained 
personnel over a 15-to-20-minute period. The Structured Interview Guide for the HAM-A 
(SIGH-A) will be used. A copy of the HAM-A is present in Appendix A. 
10.3.1.2 Clinical Global Impression Scales 
The CGI scale is a clinician-rated scale assessment of the clinician’s view of the subject’s global 
health prior to and after participation in a clinical study. The scale assesses the clinician’s 
knowledge of the subject’s history, psychosocial circumstances, symptoms, behavior and the effect 
of these parameters on the subject’s capability to function since the last visit with the subject. The 
CGI consists of 2 components, severity (CGI-S) and improvement (CGI-I). The severity 
component consists of 1 question that assesses the disease severity of the patient population and is 
on a scale of 1 to 7 ranging from normal (1) to extremely ill (7). The improvement component 
evaluates the change of the subject’s condition from the Baseline and is on a scale of 1 to 7 ranging 
from very much improved (1) to very much worse (7). The time frame for rating is the past week. 
10.3.1.3 Patient Global Impression of Change 
The Patient Global Impression of Change (PGI-C) is a self-administered instrument that measures 
change in subjects’ overall improvement with treatment on a scale where 1 = “very much 
improved” and 7 = “very much worse.”  
Very Much Improved 
1 
Much Improved 
2 
Minimally Improved 
3 
No Change 
4 
Minimally Worse 
5 
Much Worse
6 
Very Much Worse 
7 
10.3.1.4 Adjustment Disorder New Module Scale 
ADNM is a newer scale that has been validated for classification of severity of AjD.47 It consists 
of an 18-item stressful life event checklist and a list of 20 statements about which reactions these 
types of events can trigger. Subjects are asked to indicate how often the respective statement 

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applies to them on a 4-point scale (“never” to “often”). For each statement subjects are then asked 
how long they have been having this reaction (< 1 month, 1-6 months, 6 months-2 years).48 A copy 
of the ADNM is present in Appendix B. 
10.3.1.5 International Adjustment Disorder Questionnaire 
The International Adjustment Disorder Questionnaire is a recently validated questionnaire to 
measure AjD symptoms defined by the new International Classification of Disorders (ICD-11) 
definition.48The subject completes a 9-item checklist of potential stressful events, and if they have 
experienced any stressful events they then complete a 7-item list of potential problems suffered 
over the last month (preoccupation symptom) and 3-item list of potential social impacts from the 
stressors (failure to adapt). A copy of the IADQ is present in Appendix C. 
10.3.2 Safety Variables 
Safety assessments will include the evaluation of AEs, clinical laboratory assessments, vital signs, 
12-lead ECGs, and physical examinations. 
10.3.2.1 Clinical Laboratory Safety Assessments 
10.3.2.1.1 Clinical Laboratory Tests to be Performed 
Samples for the following laboratory tests will be collected at the time points specified in the 
schedule of events (Table 2-1). 
All laboratory tests will be performed on site during the study, and include the following: 
Chemistry Panel: 
alanine aminotransferase, aspartate aminotransferase, albumin, calcium, 
chloride, alkaline phosphatase, bicarbonate, cholesterol, creatine kinase, 
creatinine, direct bilirubin, lactate dehydrogenase, magnesium, globulin, 
glucose, gamma-glutamyl transferase, indirect bilirubin, phosphorous, 
potassium, sodium, total bilirubin, total protein, triglycerides, urea 
nitrogen, uric acid 
Hematology/ 
Hemogram Panel: 
hematocrit, hemoglobin, mean corpuscular hemoglobin, mean corpuscular 
concentration, mean corpuscular volume, platelets, red blood cell count, 
white blood cell count, red blood cell morphology 
Hematology 
Differential Panel: 
basophils, eosinophils, lymphocytes, monocytes, neutrophils 
Urinalysis 
macroscopic 
panel:  
bilirubin, blood, clarity, color, glucose, ketones, leucocyte esterase, nitrite, 
pH, protein, specific gravity, urobilinogen 
Urine Pregnancy 
Test: 
for all female subjects of childbearing potential 
Urine Drug 
Screen: 
tricyclic 
antidepressants, 
opiates, 
cocaine, 
benzodiazepines, 
amphetamines, 
barbiturates, 
cannabinoids, 
methadone, 
methamphetamine, phencyclidine, propoxyphene, buprenorphine, ecstasy, 
oxycodone 

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Other: 
prolactin 
thyroid stimulating hormone
free thyroxine (T4) (if thyroid stimulating hormone is above the upper or 
below the lower normal limits, then free thyroxine will automatically be 
performed) 
The local laboratory should be used for any unscheduled and follow-up labs, if needed. This 
includes any confirmatory pregnancy or drug screens for positive urine tests. Additional urine and 
blood samples may be collected for further evaluation of safety as warranted by the Investigator’s 
judgment. 
Results and reports from the local laboratory should be filed with the source documents for each 
subject. The local laboratory will provide results to the study site staff as soon as they are available 
and will be provided to sponsor or designated data manager within agreed timelines. 
Any laboratory value outside the normal range will be flagged for the attention of the Investigator, 
who must indicate whether the value is of clinical significance. If the result of any laboratory test 
performed during Screening (Visit 1) or Baseline (Visit 2) is clinically significant, the subject 
should not be randomized at Visit 2. However, any abnormal result may be repeated to confirm 
the finding before excluding the subject from potential inclusion in the study. In addition, subjects 
should be excluded if they have any other abnormal laboratory test at Screening (Visit 1) that, in 
the Investigator’s judgment, is medically significant in that it would impact the safety of the 
subject, the conduct of the study, or the interpretation of the study results. 
Follow-up/unscheduled laboratory tests may be performed on clinically significant abnormalities 
as indicated by the Investigator. Unscheduled laboratory tests may be repeated at any time at the 
discretion of the Investigator for appropriate medical care. 
10.3.2.1.2 Specimen Handling Requirements 
The transmission of infectious agents may occur through contact with contaminated needles and 
blood or blood products. Consequently, appropriate blood and body fluid precautions should be 
employed by all study personnel involved in the collection of blood and handling of specimens in 
both the clinic and laboratory settings. Refer to current recommendations of the appropriate 
authorities. 
In addition to appropriate handling of subject samples, specific regulations exist regarding the 
shipment of biologic/etiologic samples. Procedures and regulations for the packaging and shipping 
of infectious samples are outlined in the study laboratory manual or other appropriate reference. 
The Investigator is responsible for ensuring that all study samples that are to be transported to 
another location are packed and shipped appropriately according to the applicable regulations. 
10.3.2.1.3 Evaluation of Clinical Laboratory Values 
The normal ranges of values for the clinical laboratory assessments in this study will be provided 
by the responsible laboratory and submitted to VistaGen Therapeutics, Inc. prior to the beginning 
of the study. They will be regarded as the reference ranges on which decisions will be made. 

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If a laboratory value is out of the reference range, it is not necessarily clinically relevant. The 
Investigator must evaluate the out-of-range values and record his or her assessment of the clinical 
relevance in the appropriate eCRF. 
All clinical laboratory values that in the Investigator’s opinion show clinically relevant or 
pathological changes during or after termination of treatment must be reported as AEs and 
followed, as described in Section 11.2.5. 
All measurements described in this section are recognized standard methods. 
10.3.2.2 Clinical Examinations 
10.3.2.2.1 Vital Signs 
Vital signs, including heart rate, respiratory rate, and seated systolic and diastolic blood pressure 
will be measured after the subject has been in a seated position for 5 minutes. Temperature will 
also be measured. 
10.3.2.2.2 Twelve-lead Electrocardiogram 
A standard 12-lead ECG will be performed after the subject has been supine for at least 5 minutes. 
All ECG recordings will be identified with the subject number, initials, date, and time of the 
recording and will be attached to the subject’s eCRF. 
10.3.2.2.3 Physical Examination 
A complete physical examination (excluding the genitourinary examination) will be performed as 
indicated in the schedule of events (Table 2-1). The physical examination will include 
measurement of weight and height, and an examination of the nasal passages. 
10.3.2.2.4 Columbia-Suicide Severity Rating Scale 
The C-SSRS is a semi structured interview that captures the occurrence, severity, and frequency 
of suicide-related thoughts and behaviors during the assessment period. The interview includes 
definitions and suggested questions to solicit the type of information needed to determine if a 
suicide-related thought or behavior has occurred. The C-SSRS has a “baseline” version which will 
be completed at Screening (Visit 1) 
 
 There are a maximum of 19 items to be completed: 7 that are required, 
10 potential additional items if there is a positive response to a required item, and 2 items for 
suicide/suicide behavior present during the interview. The C-SSRS uses dichotomous scales (i.e., 
yes or no), Likert scales, and text or narrative to further describe the thoughts or behaviors. 
10.3.2.3 Adverse Events 
The definitions and management of AEs, and any special considerations for AEs, are provided in 
Section 11. 

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10.3.2.4 Penn Physician Withdrawal Checklist 
The PWC-20 is a 20-item simple instrument for assessing anxiolytic discontinuation symptoms. It 
consists of 20 questions related to withdrawal from benzodiazepines or other anti-anxiety 
compounds. The symptoms measured are based on those that are potentially related to anxiolytic 
withdrawal: gastrointestinal, mood, sleep, motor, somatic, perception and cognition. The questions 
will cover any symptoms that might occur during the week following discontinuation of PH94B. 
The PWC-20 scores will be compared between placebo and PH94B.49 The PWC-20 is provided in 
Appendix D.  

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11. ADVERSE EVENTS
It is the responsibility of the Investigator at the site to oversee the safety of the study at his/her site. 
This safety monitoring will include careful assessment and appropriate reporting of SAEs as noted 
below. Medical monitoring will include a regular assessment of the number and type of SAEs. 
11.1. Definitions 
11.1.1 Adverse Events 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding, for example), symptom, or disease temporally associated with the 
use of a medicinal product, whether or not related to the medicinal product. 
Pre-existing diseases or conditions will not be considered AEs unless there is an increase in the 
frequency or severity, or a change in the quality, of the disease or condition. (Worsening of a 
pre-existing condition is considered an AE.) 
Pregnancy is not considered an AE, but it is an important medical event, which must be followed
up as described in Section 11.3.1. 
11.1.2 Unexpected Adverse Events
An expected AE is one for which the nature or severity is consistent with the known AE profile of 
the product. For a pre-approval test product, the known information is contained in the IB. For a 
marketed product, the known information is contained in the current package insert for the product. 
An unexpected AE (UAE) is one for which the nature or severity of which is not consistent with 
the applicable product information (e.g., Investigator’s Brochure for an unapproved IP or package 
insert/summary of product characteristics for an approved product). For example, hepatic necrosis 
would be unexpected (greater severity) if the IB only listed elevated hepatic enzymes or hepatitis. 
Likewise, cerebral thromboembolism and cerebral vasculitis would be unexpected (greater 
specificity) if the IB only listed cerebral vascular accidents. 
Furthermore, reports that add significant information on specificity or severity of a known, already 
documented adverse reaction constitute unexpected events. Examples would be (a) acute renal 
failure as an expected adverse reaction with a subsequent new occurrence of interstitial nephritis 
(interstitial nephritis would be unexpected) and (b) hepatitis with a first occurrence of fulminant 
hepatitis (fulminant hepatitis would be unexpected.) 
11.1.3 Serious Adverse Events 
An SAE is any untoward medical occurrence that at any dose: 
 results in death 
 is life-threatening 
NOTE: The term “life-threatening” in the definition of “serious” refers to an event in which 
the patient was at risk of death at the time of the event; it does not refer to an event that 
hypothetically might have caused death if it were more severe. 

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 requires inpatient hospitalization or prolongation of existing hospitalization 
An elective hospital admission to treat a condition present before exposure to the IP, or a 
hospital admission for a diagnostic evaluation of an AE, does not qualify the condition or 
event as an SAE. 
results in persistent or significant disability/incapacity
 is a congenital anomaly 
NOTE: A congenital anomaly in an infant born to a mother who was exposed to the IP 
during pregnancy is an SAE. However, a newly diagnosed pregnancy in a subject that has 
received an IP is not considered an SAE unless it is suspected that the IP(s) interacted with 
a contraceptive method and led to the pregnancy. 
is an important medical event
NOTE: Medical and scientific judgment should be exercised in deciding whether it is 
appropriate to consider other situations serious, such as important medical events that may 
not be immediately life-threatening or result in death or hospitalization but may jeopardize 
the patient or may require intervention to prevent one of the other outcomes listed in the 
definition above. Examples of such events are intensive treatment in an emergency room 
or at home for allergic bronchospasm, blood dyscrasias, or convulsions that do not result 
in hospitalization, development of drug dependency, or drug abuse. 
11.1.4 Significant Adverse Events
Other significant AEs are defined as marked hematological and other laboratory abnormalities 
(other than those meeting the definition of serious) and any events that led to an intervention, 
including withdrawal of test drug, dose reduction, or significant additional concomitant therapy. 
11.1.5 Treatment-Emergent Adverse Events 
Treatment-emergent AEs are defined as: 
 AEs with onset at the time of or following the start of treatment with IP through the 
Follow-up Visit or 
 AEs starting prior to the start of treatment but increasing in severity or relationship at the 
time of, or following, the start of treatment with IP through the Follow-up Visit. 
11.2. Event Assessment and Follow-up of Adverse Events 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits 
and interviews of a study subject presenting for medical care or upon review by a study monitor.
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured 
on the appropriate eCRF. Information to be collected includes event description, time of onset, 
clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All 
AEs occurring while on study must be documented appropriately regardless of relationship. All 
AEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the subject is screened will be considered as 
baseline and not reported as an AE. However, if the study subject’s condition deteriorates at any 
time during the study, it will be recorded as an AE. 

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Changes in the severity of an AE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode.
The Investigator will record all reportable events with start dates occurring any time after informed 
consent is obtained until 7 days after the last day of study participation. At each study visit, the 
Investigator will inquire about the occurrence of AE/SAEs since the last visit. Events will be 
followed for outcome information until resolution or stabilization. 
11.2.1 Assessment 
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE described previously. At each visit, the subject will be allowed 
time to spontaneously report any issues since the last visit or evaluation. The Investigator will then 
monitor and/or ask about or evaluate AEs using nonleading questions, such as 
 “How are you feeling?” 
 “Have you experienced any issues since your last visit?” 
 “Have you taken any new medications since your last visit?” 
Any clinically relevant observations made during the visit will also be considered AEs. 
11.2.2 Evaluation 
11.2.2.1 Severity of Adverse Events 
The clinical severity of an AE will be classified as: 
Mild
An event that is easily tolerated by the subject, causing minimal discomfort, 
and not interfering with everyday activities 
Moderate
An event that is sufficiently discomforting to the extent of interfering with 
normal everyday activities
Severe 
An event that prevents the subject from performing normal everyday activities
It is important to distinguish between severe AEs and SAEs. Severity is a classification of intensity 
whereas an SAE is an AE that meets serious criteria, as described in Section 11.1.3. 
11.2.2.2 Seriousness 
The Investigator is to evaluate whether the AE meets serious criteria, as described in 
Section 11.1.3. 

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11.2.2.3 Actions Taken 
Action(s) taken may consist of: 
Dose not changed
An indication that a medication schedule was maintained. 
Drug withdrawn 
An indication that a medication schedule was modified through 
termination of a prescribed regimen of medication. 
Not applicable
Determination of a value is not relevant in the current context.
Unknown 
Not known, not observed, not recorded, or refused. 
11.2.2.4 Outcome at the Time of Last Observation 
The outcome at the time of last observation will be classified as: 
 Recovered/resolved 
 Recovered/resolved with sequelae 
 Recovering/resolving 
 Not recovered/not resolved 
 Fatal* 
 Unknown 
*Investigators should only select fatal as an outcome when the AE results in death. If more than 
one AE is judged to be possibly related to the subject’s death, the outcome of death should be 
indicated for each such AE. Although “fatal” is usually an event outcome, events such as sudden 
death or unexplained death should be reported as SAEs. 
11.2.2.5 Adverse Event Relationship to Investigational Product 
The Investigator must assess each AE’s relationship to the IP. The categories for classifying the 
Investigator’s opinion of the relationship are as follows: 
Related 
A reasonable possibility exists of a relationship between the AE and IP. 
Not related
No reasonable possibility exists of a relationship between the AE and IP. 
Medical judgment should be used to determine the relationship, considering all relevant factors, 
including pattern of reaction, temporal relationship, relevant medical history, and confounding 
factors such as co-medication or concurrent diseases. 
11.2.3 Documentation 
All AEs that occur within the period of observation for the study must be documented in the eCRF 
with the following information, where appropriate. (The period of observation for the study is 
described in Section 11.2.) 
 AE name or term 
 When the AE first occurred (start date and time) 

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 When the AE stopped (stop date and time or an indication of “ongoing”) 
 Severity of the AE 
 Seriousness (hospitalization, death, etc.) 
 Actions taken 
 Outcome 
 Investigator opinion regarding the AE relationship to the IP(s) 
11.2.4 Treatment of Adverse Events 
Adverse events that occur during the study will be treated, if necessary, by established standards 
of care. If such treatment constitutes a deviation from the protocol, the subject should be withdrawn 
from the study and the reason must be documented in the eCRF. The decision about whether the 
subject may continue in the study will be made by the sponsor after consultation with the 
Investigator and/or Medical Monitor. 
If AEs occur in a subject that are not tolerable, the Investigator must decide whether to stop the 
subject’s involvement in the study and/or treat the subject. Special procedures may be 
recommended for the specific IP, such as the collection of a serum sample for determining blood 
concentrations of IP, specific tapering procedures, or treatment regimens, as appropriate. 
For double- or triple-blinded studies, it is not necessary to unblind a subject’s treatment assignment 
in most circumstances, even if an SAE has occurred. If unblinding is necessary, see Section 9.6 
for a description of the unblinding procedures. 
11.2.5 Follow-up 
Any AE will be followed to a satisfactory resolution, until it becomes stable, or until it can be 
explained by another known cause(s) (i.e., concurrent condition or medication) and clinical 
judgment indicates that further evaluation is not warranted. All findings relevant to the final 
outcome of an AE must be reported in the subject’s medical record and recorded on the eCRF 
page. 
11.2.6 Reporting 
11.2.6.1 Serious Adverse Events 
The Investigator or designee must report all SAEs promptly to Premier Research within 24 hours 
of first becoming aware of the event by completing, signing, and dating the Serious Adverse Event 
Report Form, verifying the accuracy of the information recorded in the form with the source 
documents and eCRF, and sending the SAE Report Form to Premier Research by one of the 
following methods: 
 

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This written report should be submitted on the SAE form provided for this purpose. At the time of 
first notification, the Investigator or designee should provide the following information, if 
available: 
 Protocol number 
 Reporter (study site and Investigator) 
 Subject’s study number 
 Subject’s year of birth 
 Subject’s gender 
 Date of first dose of IP(s) 
 Date of last dose of IP(s), if applicable 
 Adverse event term 
 Date of occurrence of the event 
 A brief description of the event, outcome to date, and any actions taken 
 The seriousness criteria(on) that were met 
 Concomitant medication at onset of the event 
 Relevant medical history information 
 Relevant laboratory test findings 
 Investigator’s opinion of the relationship to IP(s) (“Is there a reasonable possibility that the 
IP caused the SAE? Yes or No?”) 
 Whether and when the Investigator was unblinded as to the subject’s treatment assignment 
Any missing or additional relevant follow-up information concerning the SAE should be sent to 
the sponsor/sponsor representative via the same contact details above as soon as possible on a 
follow-up SAE Report Form, together with the following minimal information (initial report, AE, 
date of occurrence, subject identification [ID], study ID, IP, and site number); this will allow the 
follow-up information to be linked to the initial SAE report. 
Specific information may be requested by the 
 
 
The Investigator is required to comply with applicable regulations (including local laws and 
guidances) regarding the notification of his or her health authorities, IRB, principal and 
coordinating investigators, study investigators, and institutions. Each Investigator is obligated to 
learn about the reporting requirements for investigators in his/her country. The study monitor may 
be able to assist with this. 
11.2.6.2 Nonserious Adverse Events 
Nonserious AEs will be recorded in the eCRF and reported by Premier Research to the sponsor in 
accordance with the study-specific safety management plan. 

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11.3. Special Considerations 
11.3.1 Pregnancy 
All women of childbearing potential who participate in the study should be counseled on the need 
to practice adequate birth control and on the importance of avoiding pregnancy during study 
participation. Women should be instructed to contact the Investigator or study staff immediately 
if pregnancy occurs or is suspected. 
Pregnancy testing will be conducted prior to administration of the IP on every woman of 
childbearing potential. A woman who is found to be pregnant at Screening (Visit 1) will be 
excluded from the study and considered to be a screening failure. 
A woman who becomes pregnant during IP treatment or within 7 days of discontinuing the IP will 
be immediately discontinued from study participation. The Investigator must report the pregnancy 
within 48 hours of learning of the pregnancy, to Premier Research Pharmacovigilance using the 
Pregnancy Data Collection Form via the same fax number and/or email address as for SAE 
reporting. The Investigator should contact the designated individual(s) who receive SAE 
notification and record information related to the pregnancy on an Exposure in Utero form 
provided by the sponsor or its designee. 
Early Termination Visit assessments are required as soon as possible after learning of the 
pregnancy. The Investigator is also responsible for following the pregnancy until delivery or 
termination. These findings must be reported on the Exposure in Utero form and forwarded to the 
designated individual(s). The event meets the SAE criterion only if it results in a spontaneous 
abortion or a congenital anomaly. 
11.3.2 Overdose 
The maximal dose of PH94B should not be exceeded during the study. Overdose that occurs during 
the study will be treated and documented as an AE/UAE/SAE if it fulfills the criteria. The 
information contained therein should include study site identification, reporter identification, 
subject identification, IP, dose, action taken (e.g., supportive measures or therapy), and any 
comments. If the overdose does not result in an AE, it should be reported in the eCRF. 

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12. DATA SAFETY MONITORING BOARD 
A data safety monitoring board will not be used in this study. 

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13. STATISTICS 
13.1. Statistical Analysis 
This section presents a summary of the planned statistical analyses. 
A statistical analysis plan (SAP) will be finalized and approved before final database lock and 
unblinding of the randomization code. 
Unless otherwise indicated, all testing of statistical significance will be two-sided, and a difference 
resulting in a p 
 0.05 will be considered statistically significant. 
The data will be summarized in tables, as appropriate, showing the number of subjects with non-
missing data (n), mean, standard deviation, median, minimum, and maximum for continuous data 
and showing counts and percentage for categorical data. Data will also be listed as deemed 
appropriate. All statistical analyses will be performed, and data appendices will be created by using 
SAS. Details of the statistical approach for each endpoint will be provided in the SAP. 
13.1.1 Analysis Populations 
The following 2 analysis populations are planned for this study: 
 Intent-to-treat (ITT) population: All subjects who are randomized and have documented 
one dose of IP at Visit 2 will be included in the ITT population. All efficacy analyses will 
be performed using the ITT population. 
 Safety population: All subjects who are dispensed IP and reported administering at least 
one dose of IP will be included in the safety population. All safety analyses will be 
performed using the safety population. 
Inclusion in the analysis populations will be determined prior to database lock. 
If a subject is randomized incorrectly or is administered the incorrect IP, analyses of the ITT 
population will be based on the assigned treatment whereas all other analyses will be based on the 
actual treatment. 
13.1.1.1 Estimand Framework 
The target of estimation to address the scientific question of interest (posed by the primary 
objective for this study): 
In adults with AjDA, is the difference in mean change from baseline anxiety severity (as 
measured by HAM-A total score) greater for PH94B-treated subjects compared to 
placebo-treated subjects, after 4 weeks of treatment? 
is defined by the following attributes: 
1. Population: Adults with AjDA (as defined by inclusion and exclusion criteria). 
2. Treatment: PH94B compared to placebo control. 

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3. Variable of interest: Change in subject reported severity of anxiety as measured by change 
from baseline in HAM-A total score using the SIGH-A, after 4 weeks of randomized 
treatment with the study medication. 
4. Population-level summary measure: Difference in mean HAM-A total score between 
PH94B-treated and placebo-treated subjects after 4 weeks of treatment. 
5. Anticipated intercurrent event: Treatment discontinuation prior to the planned assessment 
time frame. 
Strategies for handling potential intercurrent events (ICE) are summarized in Table 13-1. 
Table 13-1: 
Strategies for Handling Intercurrent Events 
ICE 
Strategy for Addressing ICE 
Treatment Discontinuation 
following randomization but 
prior to Week 4 
While on Treatment Strategy 
The research objectives seek to understand the response to 
PH94B compared to placebo while subjects are actively using 
the study medication. Subjects who discontinue will undergo 
an Early Termination Visit and provide all Visit 6 outcome 
measures and safety assessments for the efficacy analysis.  
Treatment Discontinuation 
following randomization but 
prior to Week 4 (subject lost 
to follow-up) 
Hypothetical Strategy 
Measurement following ICE is unavailable and will be 
considered missing. Multiple imputation of Visit 6 efficacy 
measures using important subject variables and treatment 
assignment will be conducted and subjected to sensitivity 
analysis. (complete case comparison and assumption of 
treatment failure using 0 change from baseline HAM-A). 
Use of prohibited medication 
prior to Week 4 
Hypothetical Strategy 
Measurement following ICE is not of interest and will be 
considered missing. Multiple imputation of Visit 6 efficacy 
measures using important subject variables and treatment 
assignment will be conducted and subjected to sensitivity 
analyses (complete case comparison and assumption of 
treatment failure using 0 change from baseline HAM-A).
Abbreviations: HAM-A = Hamilton Anxiety Scale; ICE = intercurrent event 
13.1.2 Study Subjects and Demographics 
13.1.2.1 Disposition and Withdrawals 
The numbers of subjects randomized, completing, and withdrawing, along with reasons for 
withdrawal, will be tabulated overall and by treatment group. The number of subjects in each 
analysis population will be reported. 

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13.1.2.2 Protocol Deviations 
A protocol deviation is any non-compliance with the clinical trial protocol or International Council 
for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good 
Clinical Practice (GCP) requirements. The non-compliancemay be either on the part of the subject, 
the Investigator, or the study site staff. As a result of deviations, corrective actions are to be 
developed by the site and implemented promptly. 
Documentation of the deviations and corrective actions will be included in the data quality 
assessment during blinded review. 
It is the responsibility of the site Investigator to use continuous vigilance to identify and report 
deviations within 2 working days of identification of the protocol deviation, or within 2 working 
days of the scheduled protocol-required activity. All deviations must be addressed in study source 
documents, reported to the sponsor. Protocol deviations must be sent to the reviewing IRB per 
their policies. The site Investigator is responsible for knowing and adhering to the reviewing IRB 
requirements. Further details about the handling of protocol deviations will be included in the 
protocol deviation guidance plan. 
13.1.2.3 Demographics and Other Baseline Characteristics 
These analyses will be conducted for all analysis populations. 
Demographic variables will include age, sex, height, and weight. Information on race and ethnicity 
will be collected for any eventual analysis of differences in response to the IPs, in accordance with 
local regulatory requirements. Baseline subject characteristics will include medical and psychiatric 
history, MINI findings, and physical examination findings. 
Prior and concomitant medications will be summarized by treatment group, by the number and 
percentage of subjects taking each medication, classified using World Health Organization Drug 
Dictionary Anatomical Therapeutic Chemical classes and preferred terms. 
13.1.3 Exposure and Compliance 
Investigational product administration will be summarized in terms of number of doses received 
(PH94B and placebo). Descriptive statistics for categorical data will be provided by treatment 
group. 
13.1.4 Efficacy Analysis 
Efficacy variables will be summarized and analyzed using the ITT population, unless otherwise 
specified. 
Details of the statistical approach and code for analysis of each endpoint will be provided in the 
SAP. 

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13.1.4.1 Efficacy Endpoints 
Primary Endpoint 
The primary efficacy endpoint of the study is change from baseline in anxiety level as measured 
by the HAM-A for the PH94B-treated group compared to placebo-treated group at the end of the 
4-week treatment period.
Secondary Endpoints 
The secondary efficacy endpoints are as follows: 
 Individual subject improvement as assessed by the CGI-I. Values for comparison will be 
the proportion of “responders” in each group, defined as subjects receiving scores of 1 
(Very much improved) or 2 (Much improved) at end of treatment 
 Individual subject improvement as assessed by the subject's self-assessment of 
improvement (by PGI-C) at the end of treatment compared to baseline. Values for 
comparison will be the proportion of “responders” in each group, defined as subjects 
receiving scores of 1 (Very much improved) or 2 (Much improved) at end of treatment  
 Individual subject improvement on the ADNM scale at the end of treatment compared to 
baseline 
 Individual subject improvement on the IADQ at end of treatment compared to baseline 
 
 
 
 
 
 
 
 
13.1.4.2 Primary Analysis 
An analysis of covariance model with treatment group as factor and baseline HAM-A as covariate 
will be used to test the null hypothesis that there is no difference between PH94B- and placebo-
treated subjects in change from baseline to end of treatment in HAM-A scores. (SAS PROC 
MIXED, version 9.4). 
13.1.4.3 Secondary Analyses 
CGI-I and PGI-C at end of treatment will be analyzed using a normal approximation test for the 
difference between 2 binomial proportions. The null hypothesis to be tested is that there is no 
difference between PH94B- and placebo-treated subjects. (SAS PROC FREQ, version 9.4). 
Change from baseline to Week 4 in ADNM total score will be analyzed analogously to the primary 
endpoint. 
Change from baseline to Week 4 in IADQ total score will be analyzed analogously to the primary 
endpoint. 

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13.1.5 Safety and Tolerability Analyses 
Safety in this study will be determined from evaluation of AEs, clinical laboratory assessments, 
vital signs assessments, physical examinations including examination of the nasal passages, and 
ECGs. Specific visits for obtaining clinical laboratory assessment samples are listed in the 
schedule of events (Table 2-1). Details of clinical laboratory tests are provided in 
Section 10.3.2.1.1. 
Descriptive statistics will be used to summarize safety and tolerability of PH94B (3.2 µg) as 
measured by reports of AEs and SAEs, changes in clinical laboratory values, ECGs, vital signs, 
and physical examinations, as well as suicidal ideation (as documented using the C-SSRS and 
MADRS scores), and withdrawal effects (PWC-20). 
Safety analyses will be conducted using data from the safety population (as defined in 
Section 13.1.1). 
13.1.5.1 Adverse Events 
All AEs will be coded using the most recent version of Medical Dictionary for Regulatory 
Activities. 
Treatment-emergent AEs are defined as: 
 AEs with onset at the time of or following the start of treatment with IP through the 
Follow-up Visit or 
 AEs starting prior to the start of treatment but increasing in severity or relationship at the 
time of, or following, the start of treatment with IP through the Follow-up Visit 
Adverse events will be classified by time of occurrence group assignment to more clearly identify 
those arising after exposure to placebo only and those arising after exposure to PH94B. 
The number and percentage of subjects with AEs will be displayed for each treatment group by 
system organ class and preferred term. Summaries of AEs by severity and relationship to IP will 
also be provided. Serious AEs and AEs resulting in discontinuation of IP will be summarized 
separately in a similar manner. Subject listings of AEs, SAEs, and AEs causing discontinuation of 
IP will be produced. 

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13.1.5.2 Clinical Laboratory Evaluations 
Descriptive summaries (mean, SD, median, minimum, and maximum) of actual (absolute) values 
and changes from baseline values will be presented for clinical laboratory values for each treatment 
group at each time point.
The number of subjects with clinical laboratory values categorized as below, within, or above 
normal ranges will be tabulated showing change from baseline (shift tables) for each clinical 
laboratory analyte by treatment group and by study visit. 
Laboratory values that are outside the normal range will also be flagged in the data listings and 
presented with the corresponding normal ranges. Any out-of-range values that are identified by 
the Investigator as being clinically significant will also be shown in a data listing. 
13.1.5.3 Vital Signs 
Descriptive summaries (mean, SD, median, minimum, and maximum) of actual values and 
changes from baseline will be calculated for systolic blood pressure, diastolic blood pressure, heart 
rate, and respiratory rate. 
The number of subjects with vital signs values categorized as below, within, or above normal 
ranges will be tabulated showing change from baseline (shift tables) for each parameter by 
treatment group and by study visit. Pre- and post-treatment values may also be presented with an 
analysis of mean changes from baseline. 
13.1.5.4 Twelve-lead Electrocardiograms 
The number and percentage of subjects with normal and abnormal ECG findings will be 
summarized for each treatment group at each time point. Abnormal results will be grouped as 
clinically significant and not clinically significant. 
A comparison of QT results will be presented. Summary statistics for baseline values at Screening 
(Visit 1) and Follow-up will be displayed by treatment group for QT and the QT interval corrected 
for heart rate (QTc). In addition, the number and percent of subjects in each treatment group who 
experienced a change >30 ms or a change >60 ms will be presented. 
Descriptive summaries (mean, SD, median, minimum, and maximum) will be presented for ECG 
measures of PR interval, QRS interval, QT interval, QTc interval (both correction methods), and 
heart rate for each treatment group at each time point. 
13.1.5.5 Physical Examination Findings 
The number and percentage of subjects with normal and abnormal findings in the complete 
physical examination, including nasal passages examination, will be displayed for each treatment 
group. 
13.1.6 Interim Analysis 
No interim analyses are planned. 

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13.2.
 
 
 
 
 
 
 
 
 
 
 
 

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14. STUDY CONDUCT
Steps to ensure the accuracy and reliability of data include the selection of qualified investigators 
and appropriate study sites, review of protocol procedures with the Investigator and associated 
personnel before the study, periodic monitoring visits, and meticulous data management. 
14.1. Sponsor and Investigator Responsibilities 
14.1.1 Sponsor Responsibilities 
The sponsor is obligated to conduct the study in accordance with strict ethical principles 
(Section 16). The sponsor reserves the right to withdraw a subject from the study (Section 8.3), to 
terminate participation of a study site at any time (Section 14.7), and/or to discontinue the study 
(Section 14.6).
VistaGen Therapeutics, Inc. agrees to provide the Investigator with sufficient material and support 
to permit the Investigator to conduct the study according to the study protocol. 
14.1.2 Investigator Responsibilities 
By signing the Investigator’s Agreement (Section 18.1), the Investigator indicates that he or she 
has read the protocol carefully, fully understands the requirements, and agrees to conduct the study 
in accordance with the procedures and requirements described in this protocol. 
The study will be conducted in accordance with ICH GCP and applicable United States Code of 
Federal Regulations (CFR). The Principal Investigator will assure that no deviation from, or 
changes to, the protocol will take place without prior agreement from the Investigational New 
Drug (IND) sponsor, funding agency and documented approval from the IRB, except where 
necessary to eliminate an immediate hazard(s) to the study subjects. All personnel involved in the 
conduct of this study have completed Human Subjects Protection and ICH GCP training. 
Investigators should ensure that all persons who are delegated study-related responsibilities are 
adequately qualified and informed about the protocol, the IP(s), and their specific duties within the 
context of the study. Investigators are responsible for providing VistaGen Therapeutics, Inc. with 
documentation of the qualifications, GCP training, and research experience for themselves and 
their staff as required by the sponsor and the relevant governing authorities. 
To ensure compliance with the guidelines, the study may be audited by an independent person. 
The Investigator agrees, by written consent to this protocol, to cooperate fully with compliance 
checks by allowing access to all study documentation by authorized individuals. 
14.1.3 Confidentiality and Privacy 
Subject confidentiality and privacy are strictly held in trust by the participating investigators, their 
staff, and the sponsor and their staff. This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to subjects. Therefore, the 
study protocol, documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study or the data will be released to any unauthorized 
third party without prior written approval of the sponsor. 
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB, 
regulatory agencies, or pharmaceutical company supplying study product may inspect all 

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documents and records required to be maintained by the Investigator, including, but not limited to, 
medical records (office, clinic, or hospital) and pharmacy records for the subjects in this study.
The clinical study site will permit access to such records.
The study subject’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by the reviewing IRB, institutional policies, or sponsor 
requirements. 
Study subject research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored at Premier Research. This will not include the subject’s contact 
or identifying information. Rather, individual subjects and their research data will be identified by 
a unique study identification number. The study data entry and study management systems used 
by clinical sites and by Premier Research staff will be secured and password protected. At the end 
of the study, all study databases will be de-identified and archived at Premier Research. 
14.2. Site Initiation 
Study personnel may not screen or enroll subjects into the study until after receiving notification 
from the sponsor or its designee that the study can be initiated at the study site. The study site will 
not be authorized for study initiation until: 
1. The study site has received the appropriate IRB approval for the protocol and the 
appropriate ICF. 
2. All regulatory documents have been submitted to and approved by the sponsor or its 
designee. 
3. The study site has a Clinical Trial Agreement in place. 
4. Study site personnel, including the Investigator, have participated in a study initiation 
meeting. 
14.3. Screen Failures 
Subjects who fail inclusion and/or exclusion criteria may not be rescreened for the study.  
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently entered in the study. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure subjects to meet the Consolidated Standards of Reporting 
Trials publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any SAE. 
14.4. Study Documents 
All documentation and material provided by VistaGen Therapeutics, Inc. for this study are to be 
retained in a secure location and treated as confidential material. 
14.4.1 Informed Consent 
Informed consent forms describing in detail the study intervention, study procedures, and risks are 
given to the subject and written documentation of informed consent is required prior to starting 
intervention/administering study intervention. 

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Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be IRB 
approved and the subject will be asked to read and review the document. The Investigator will 
explain the research study to the subject and answer any questions that may arise. A verbal 
explanation will be provided in terms suited to the subject’s comprehension of the purposes, 
procedures, and potential risks of the study and of their rights as research subjects. Subjects will 
have the opportunity to carefully review the written ICF and ask questions prior to signing. The 
subject should have the opportunity to discuss the study with their family or surrogates or think 
about it prior to agreeing to participate. The subject will sign the informed consent document prior 
to any procedures being done specifically for the study. Subjects must be informed that 
participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the ICF will be given to the subjects for their records. The informed consent 
process will be conducted and documented in the source document (including the date) and the 
ICF signed before the subject undergoes any study-specific procedures. The rights and welfare of 
the subjects will be protected by emphasizing to them that the quality of their medical care will 
not be adversely affected if they decline to participate in this study. 
14.4.2 Investigator’s Regulatory Documents 
The regulatory documents are listed in the Premier Research study plans. 
The regulatory documents must be received from the Investigator and reviewed and approved by 
VistaGen Therapeutics, Inc. or its designee before the study site can initiate the study and before 
VistaGen Therapeutics, Inc. will authorize shipment of IP to the study site. Copies of the 
Investigator’s regulatory documents must be retained at the study site in a secure location. 
Additional documents, including a copy of the protocol and applicable amendment(s), the PH94B 
IB, eCRF completion guidelines, copies of regulatory references, copies of IRB correspondence, 
and IP accountability records should also be retained as part of the Investigator’s regulatory 
documents. It is the Investigator’s responsibility to ensure that copies of all required regulatory 
documents are organized, current, and available for inspection. 
14.4.3 Case Report Forms 
Electronic CRFs will be designed to capture all relevant background information as well as 
objective reasons for early discontinuation when it cannot be prevented. 
By signing the Investigator’s Agreement (Section 18.1), the Investigator agrees to maintain 
accurate eCRFs and source documentation as part of the case histories for all subjects who sign an 
ICF. 
Case report forms are considered confidential documents and should be handled and stored 
accordingly. The sponsor or its designee will provide the necessary training on the use of the 
specific eCRF system used during the study to ensure that the study information is captured 
accurately and appropriately. 
To ensure data accuracy, eCRF data for individual subject visits should be completed as soon as 
possible after the visit. All requested information must be entered in the electronic data capture 
(EDC) system according to the completion guidelines provided by the sponsor or its designee. 
The eCRFs must be signed by the Investigator. These signatures serve to attest that the information 
contained in the eCRF is accurate and true. 

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14.4.4 Source Documents 
Information recorded in the EDC system should be supported by corresponding source 
documentation. Examples of acceptable source documentation include, but are not limited to, a 
record of obtaining informed consent, hospital records, clinic and office charts, laboratory notes, 
and recorded data from automated instruments, memoranda, and pharmacy dispensing records. 
14.5. Data Quality Control 
VistaGen Therapeutics, Inc. and its designees will perform quality control checks on this clinical 
study. 
14.5.1 Monitoring Procedures 
VistaGen Therapeutics, Inc. and/or its designee will conduct site visits to monitor the study and 
ensure compliance with the protocol, GCP, and applicable regulations and guidelines. The 
assigned clinical research associate(s) (CRA[s]) will visit the Investigator and study site at periodic 
intervals and maintain periodic communication. The Investigator agrees to allow the CRA(s) and 
other authorized VistaGen Therapeutics, Inc. personnel access. The CRA(s) will maintain current 
personal knowledge of the study through observation, review of study records and source 
documentation, and discussion of the conduct of the study with the Investigator and staff. While 
on site, the CRA(s) will review 
 regulatory documents, directly comparing entries in the EDC system with the source 
documents 
 consenting procedures 
 AE procedures 
 storage and accountability of IP and study materials 
The CRA will ask for clarification and/or correction of any noted inconsistencies. Procedures for 
correcting eCRFs are described in the Premier Research study plans. As representatives of the 
sponsor, CRAs are responsible for notifying project management of any noted protocol deviations. 
By signing the Investigator’s Agreement (Section 18.1), the Investigator agrees to meet with the 
CRA(s) during study site visits; to ensure that study staff is available to the CRA(s) as needed; to 
provide the CRA(s) access to all study documentation, to the clinical supplies dispensing and 
storage area; and to assist the monitors in their activities, if requested. Further, the Investigator 
agrees to allow VistaGen Therapeutics, Inc. or designee auditors or inspectors from regulatory 
agencies to review records and to assist the inspectors in their duties, if requested.
Additional details on monitoring will be described in the clinical monitoring plan. 
14.5.2 Data Management 
VistaGen Therapeutics, Inc. or designee will be responsible for activities associated with the data 
management of this study. The standard procedures for handling and processing records will be 
followed per GCP and Premier Research’s standard operating procedures. A comprehensive data 
management plan will be developed, including a data management overview, description of 
database contents, annotated eCRF, and consistency checks. 

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Study site personnel will be responsible for providing resolutions to all data queries. The 
Investigator will be required to document electronic data review to ensure the accuracy of the 
corrected and/or clarified data. Procedures for soliciting and documenting resolution to data 
queries are described in the Premier Research study plans. 
14.5.3 Quality Assurance/Audit 
This study will be subject to audit by VistaGen Therapeutics, Inc., or its designee. Audits may be 
performed to check compliance with GCP guidelines and can include:
 site audits 
 Trial Master File audits 
 database audits 
 document audits (e.g., protocol and/or clinical study report [CSR]) 
VistaGen Therapeutics, Inc. or its designee may conduct additional audits on a selection of study 
sites, requiring access to subject notes, study documentation, and facilities or laboratories used for 
the study. 
The study site, facilities, all data (including source data), and documentation will be made available 
for audit by quality assurance auditors and for IRB or regulatory authorities according to GCP 
guidelines. The Investigator agrees to cooperate with the auditor during the visit and will be 
available to supply the auditor with eCRFs or other files necessary to conduct that audit. Any 
findings will be strictly confidential. 
If a regulatory authority informs the Investigator that it intends to conduct an inspection, the 
Investigator shall notify VistaGen Therapeutics, Inc. immediately. 
14.6. Study Termination 
The study may be terminated by VistaGen Therapeutics, Inc.’s discretion at any time and for any 
reason. 
14.6.1 Premature Study Termination 
The study may be temporarily suspended or terminated prematurely if there is sufficient reasonable 
cause at any time by VistaGen Therapeutics, Inc., IRBs, or regulatory authorities. 
Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to study subjects, Principal Investigators, the IND sponsor, 
and regulatory authorities. If the study is prematurely terminated or suspended, the Principal 
Investigator will promptly inform study subjects and the IRB; the sponsor will provide the reasons 
for the termination or suspension. Study subjects will be contacted, as applicable, and be informed 
of changes to study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
 Determination of unexpected, significant, or unacceptable risk to subjects
 Demonstration of efficacy that would warrant stopping 
 Insufficient compliance to protocol requirements 

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 Data that are not sufficiently complete and/or evaluable 
 Determination that the primary endpoint has been met 
 Determination of futility 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB, and/or Food and Drug Administration (FDA). 
In the case of study termination, study sites may be asked to have all subjects currently 
participating in the study complete all of the assessments for Visit 6/Early Termination. 
14.7. Study Site Closure 
At the end of the study, all study sites will be closed. VistaGen Therapeutics, Inc. may terminate 
participation of a study site at any time. Examples of conditions that may require premature 
termination of a study site include, but are not limited to, the following: 
 Non-compliance with the protocol and/or applicable regulations and guidelines 
 Inadequate subject enrollment 
14.7.1 Record Retention 
The Investigator shall retain and preserve one copy of all data generated in the course of the study, 
specifically including, but not limited to, those defined by GCP as essential until: 
 Notified by VistaGen Therapeutics, Inc. that records no longer need to be retained 
 At least 2 years following the date a marketing application for the IP has been approved in 
this indication (AjDA), or the sponsor has discontinued its research with the IP, or 
 At least 2 years have elapsed since the formal discontinuation of clinical development of the 
IP. 
These documents should be retained for a longer period, however, if required by the applicable 
regulatory requirement(s) or if needed by the sponsor. 
At the end of such period, the Investigator shall notify the sponsor in writing of his or her intent to 
destroy all such material. The sponsor has 30 days to respond to the Investigator’s notice, and the 
sponsor has further opportunity to retain such materials at the sponsor’s expense. 
14.7.2 Sample Retention 
Samples may be used for purposes related to this research. The samples will be stored until the 
sponsor has determined that specimens are no longer needed, and the decision has been made that 
none of the samples needs to be reanalyzed. In addition, identifiable samples can be destroyed at 
any time at the request of the subject. 
14.8. Changes to the Protocol 
This protocol cannot be altered or changed except through a formal protocol amendment, which 
requires the written approval of VistaGen Therapeutics, Inc. The protocol amendment must be 
signed by the Investigator and approved by the IRB before it may be implemented. Protocol 
amendments will be filed with the appropriate regulatory agency(s) having jurisdiction over the 
conduct of the study. 

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14.9. Use of Information and Publication 
All information concerning PH94B, PH94B’s operations, patent applications, formula, 
manufacturing processes, basic scientific data, and formulation information supplied by VistaGen 
Therapeutics, Inc. or its designee to the Investigator, and not previously published, is considered 
confidential and remains the sole property of VistaGen Therapeutics, Inc. Case report forms also 
remain the property of VistaGen Therapeutics, Inc. The Investigator agrees to use this information 
for purposes of study execution through finalization.
The information developed in this study will be used by VistaGen Therapeutics, Inc. in connection 
with the continued development of PH94B and thus may be disclosed as required to other clinical 
investigators or government regulatory agencies. 
The information generated by this study is the property of VistaGen Therapeutics, Inc. Publication 
or other public presentation of PH94B data resulting from this study requires prior review and 
written approval of VistaGen Therapeutics, Inc. Abstracts, manuscripts, and presentation materials 
should be provided to VistaGen Therapeutics, Inc. for review at least 30 days prior to the relevant 
submission deadline. 
It is agreed that the results of the study will not be submitted for presentation, abstract, poster 
exhibition, or publication by the Investigator until VistaGen Therapeutics, Inc. has reviewed and 
commented on such a presentation or manuscript for publication. If applicable, this study will be 
registered at ClinicalTrials.gov, and results information from this study will be submitted to 
ClinicalTrials.gov. 

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15. FINAL CLINICAL STUDY REPORT 
VistaGen Therapeutics, Inc. will retain ownership of the data. 
The final CSR will be written within 1 year of completion of the clinical part of the study. This 
report will include a summary of the study results based on a statistical evaluation and clinical 
assessment of the protocol-defined endpoints. 
The final CSR may be submitted to the regulatory authorities. 

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16. ETHICAL AND LEGAL CONSIDERATIONS
16.1. Good Clinical Practice 
This study will be conducted in compliance with the April 1996 ICH Guidance for Industry GCP 
E6 (including archiving of essential study documents), the Integrated Addendum to ICH E6 (R2) 
of November 2016, and the applicable regulations of the country(ies) in which the study is 
conducted. 
16.2. Subject Information and Informed Consent and/or Assent
A properly constituted, valid IRB must review and approve the protocol, the Investigator’s ICF, 
and related subject information and recruitment materials before the start of the study. 
It is the responsibility of the Investigator to ensure that written informed consent and/or assent is 
obtained from the subject before any activity or procedure is undertaken that is not part of routine 
care. 
16.3. Approval by Institutional Review Board 
For IND studies, the minimum standards of conduct and requirements for informed consent are 
defined in the FDA regulations. 
A valid IRB must review and approve this protocol before study initiation. Written notification of 
approval is to be provided by the Investigator to the study’s project manager or designee before 
shipment of investigational drug supplies, and will include the date of the committee’s approval 
and the chairperson’s signature. This written approval must consist of a completed Premier 
Research form, IRB approval form, or written documentation from the IRB containing the same 
information. 
Until written approval by the IRB has been received by the Investigator, no subject may undergo 
any procedure not part of routine care for the subject’s condition. 
Protocol amendments must also be reviewed and approved by the IRB. Written approval from the 
IRB, or a designee, must be received by VistaGen Therapeutics, Inc. before implementation. This 
written approval will consist of a completed approval form or written documentation from the IRB 
containing the same information. 
16.4. Finance and Insurance 
Details on finance and insurance will be provided in a separate agreement between the Investigator 
and the sponsor. 

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17. REFERENCES 
1. Gradus JL, Qin P, Lincoln AK, Miller M, Lawler E, Lash TL. The association between 
adjustment disorder diagnosed at psychiatric treatment facilities and completed suicide. 
Clin Epidemiol. 2010;2:23-28. 
2. Liebowitz MR, Hanover R, Draine A, Lemming R, Careri J, Monti L. Effect of as-needed 
use of intranasal PH94B on social and performance anxiety in individuals with social 
anxiety disorder. Depress Anxiety. 2016;33(12):1081-1089. 
3. Liebowitz MR, Salman E, Nicolini H, Rosenthal N, Hanover R, Monti L. Effect of an acute 
intranasal aerosol dose of PH94B on social and performance anxiety in women with social 
anxiety disorder. Am J Psychiatry. 2014;171(6):675-682. 
4. O'Donnell ML, Agathos JA, Metcalf O, Gibson K, Lau W. Adjustment Disorder: Current 
Developments and Future Directions. Int J Environ Res Public Health. 2019;16(14):2537. 
5. Stein DJ. Pharmacotherapy of adjustment disorder: A review. World J Biol Psychiatry. 
2018;19(sup1):S46-S52. 
6. Stein DJ. Etifoxine versus alprazolam for the treatment of adjustment disorder with 
anxiety: a randomized controlled trial. Adv Ther. 2015;32(1):57-68. 
7. do Rego JL, Vaudry D, Vaudry H. The non-benzodiazepine anxiolytic drug etifoxine 
causes a rapid, receptor-independent stimulation of neurosteroid biosynthesis. PLoS One. 
2015;10(3):e0120473. 
8. Papez JW. A proposed mechanism of emotion. Arch Neurol Psychiatry. 1937;38(4):725-
743. 
9. Maclean PD. The limbic system ("visceral brain") and emotional behavior. AMA Arch 
Neurol Psychiatry. 1955;73(2):130-134. 
10. Cairncross. Olfactory bulbectomy as a model for depression. N.W. Bond ed. In: Animal 
models in psychophysiology. Academic Press, New York. 1976:99-128. 
11. Song C, leonard B. Effects of olfactory bulbectomy in the rat, alone or in combination with 
antidepressants and endogenous factor, an immune function. Hum Psychopharmacol Clin 
Exp. 1995;10(1):7-18. 
12. Croy I, Nordin S, Hummel T. Olfactory disorders and quality of life--an updated review. 
Chem Senses. 2014;39(3):185-194. 
13. Croy I, Negoias S, Novakova L, Landis BN, Hummel T. Learning about the Functions of 
the Olfactory System from People without a Sense of Smell. 2012. Plos One. 
14. Kevetter GA, Winans SS. Connections of the corticomedial amygdala in the golden 
hamster. II. Efferents of the "olfactory amygdala". J Comp Neurol. 1981;197(1):99-111. 
15. Sosulski DL, Bloom ML, Cutforth T, Axel R, Datta SR. Distinct representations of 
olfactory information in different cortical centres. Nature. 2011;472(7342):213-216. 
16. Monti-Bloch L, Jennings-White C, Dolberg DS, Berliner DL. The human vomeronasal 
system. Psychoneuroendocrinology. 1994;19(5-7):673-686. 

VistaGen Therapeutics, Inc.
Confidential
Protocol PH94B-CL029 
30-Aug-2021 
Final, Version 2.0
Page 69 of 80 
17. Sobel N, Prabhakaran V, Hartley CA, Desmond JE, Glover GH, Sullivan EV, et al. Blind 
smell: brain activation induced by an undetected air-borne chemical. Brain. 1999;122 ( Pt 
2):209-217. 
18. Grosser BI, Monti-Bloch L, Jennings-White C, Berliner DL. Behavioral and 
electrophysiological 
effects 
of 
androstadienone, 
a 
human 
pheromone. 
Psychoneuroendocrinology. 2000;25(3):289-299. 
19. Monti-Bloch L, Grosser BI. Effect of putative pheromones on the electrical activity of the 
human vomeronasal organ and olfactory epithelium. J Steroid Biochem Mol Biol. 
1991;39(4B):573-582. 
20. Monti-Bloch L, Diaz-Sanchez V, C. J-W, Berliner DL. Modulation of serum testosterone 
and autonomic function through stimulation of the male human vomeronasal organ (VNO) 
with pregna-4,20-diene-3,6-dione. J Steroid Biochem Mol Biol. 1998;65(1-6):237-242. 
21. Monti L, Liebowitz M. Neural Circuits of Anxiolytic and Antidepressant Pherine 
Molecules. Epub ahead of print. CNS Spectrums. 2020;23:1-7. 
22. Kevetter GA, Winans SS. Connections of the corticomedial amygdala in the golden 
hamster. I. Efferents of the "vomeronasal amygdala". J Comp Neurol. 1981;197(1):81-98. 
23. Swanson LW, Petrovich GD. What is the amygdala? Trends Neurosci. 1998;21(8):323-
331. 
24. Dorries KM, Adkins-Regan E, Halpern BP. Sensitivity and behavioral responses to the 
pheromone androstenone are not mediated by the vomeronasal organ in domestic pigs. 
Brain Behav Evol. 1997;49(1):53-62. 
25. Hagino-Yamagishi K. Diverse systems for pheromone perception: multiple receptor 
families in two olfactory systems. Zoolog Sci. 2008;25(12):1179-1189. 
26. Kang N, Baum MJ, Cherry JA. A direct main olfactory bulb projection to the 'vomeronasal' 
amygdala in female mice selectively responds to volatile pheromones from males. Eur J 
Neurosci. 2009;29(3):624-634. 
27. Pape HC, Jungling K, Seidenbecher T, Lesting J, Reinscheid RK. Neuropeptide S: a 
transmitter system in the brain regulating fear and anxiety. Neuropharmacology. 
2010;58(1):29-34. 
28. Pro-Sistiaga P, Mohedano-Moriano A, Ubeda-Banon I, Del Mar Arroyo-Jimenez M, 
Marcos P, Artacho-Perula E, et al. Convergence of olfactory and vomeronasal projections 
in the rat basal telencephalon. J Comp Neurol. 2007;504(4):346-362. 
29. Mohedano-Moriano A, de la Rosa-Prieto C, Saiz-Sanchez D, Ubeda-Banon I, Pro-Sistiaga 
P, de Moya-Pinilla M, et al. Centrifugal telencephalic afferent connections to the main and 
accessory olfactory bulbs. Front Neuroanat. 2012;6:19. 
30. Sokolowski K, Corbin JG. Wired for behaviors: from development to function of innate 
limbic system circuitry. Front Mol Neurosci. 2012;5:55. 
31. Tovote P, Fadok JP, Luthi A. Neuronal circuits for fear and anxiety. Nat Rev Neurosci. 
2015;16(6):317-331. 

VistaGen Therapeutics, Inc.
Confidential
Protocol PH94B-CL029 
30-Aug-2021 
Final, Version 2.0
Page 70 of 80 
32. Schaal B, Coureaud G, Langlois D, Ginies C, Semon E, Perrier G. Chemical and 
behavioural 
characterization 
of 
the 
rabbit 
mammary 
pheromone. Nature. 
2003;424(6944):68-72. 
33. Nuss P. Anxiety disorders and GABA neurotransmission: a disturbance of modulation. 
Neuropsychiatr Dis Treat. 2015;11:165-175. 
34. Savic I, Berglund H, Gulyas B, Roland P. Smelling of odorous sex hormone-like 
compounds causes sex-differentiated hypothalamic activations in humans. Neuron. 
2001;31(4):661-668. 
35. Smeets MAM, Veldhuizen MG, Galle S, Gouweloos J, de Haan AJA, Vernooij J, et al. 
Sense of smell disorder and health-related quality of life. Rehabil Psychol. 2009;54(4):404-
412. 
36. Aydogan U, Aydogdu A, Akbulut H, Sonmez A, Yuksel S, Basaran Y, et al. Increased 
frequency of anxiety, depression, quality of life and sexual life in young hypogonadotropic 
hypogonadal males and impacts of testosterone replacement therapy on these conditions. 
Endocr J. 2012;59(12):1099-1105. 
37. Monti L, Nicolini H, Liebowitz MR, Hanover R. A Placebo Controlled Trial of PH10: Test 
of a New Rapidly Acting Intranasally Administered Antidepressant. Br J Pharm Res. 
2020;4(6):2157-2168.. 
38. Rodriguez I, Greer CA, Mok MY, Mombaerts P. A putative pheromone receptor gene 
expressed in human olfactory mucosa. Nat Genet. 2000;26(1):18-19. 
39. Grus WE, Shi P, Zhang YP, Zhang J. Dramatic variation of the vomeronasal pheromone 
receptor gene repertoire among five orders of placental and marsupial mammals. Proc Natl 
Acad Sci U S A. 2005;102(16):5767-5772. 
40. Monti-Bloch L. Patch recorded isolated adult human vomeronasal organ cells are 
electrically excitable and respond to skin steroidal substances androsta-4,16-dien-3-one 
and estra-1,3,5(10),16-tetraen-3-ol. Chemical Senses. 1995;20(6):745. 
41. Monti-Bloch L, Jennings-White C, Berliner DL. The human vomeronasal system. A 
review. Ann N Y Acad Sci. 1998;855:373-389. 
42. Liebowitz MR, Salmán E, Rosenthal N, Nicolini H, Monti L. Evaluation of a Unique 
Nanogram-Dose Intranasal Aerosol for the Acute Management of the Symptoms of Social 
Anxiety Disorder. in New Clinical Drug Evaluation Unit Conference. 2011. Boca Raton, 
FL. 
43. Winegar B, Monti L. Pherines increase cytosolic Ca in isolated living human vomeronasal 
chemosensory neurons. ACHEMS abstract. 2003. 
44. Herman R, Monti-Bloch L. Human VNO cDNA libraries: Pertusis toxin blockade of 
human VNO receptors (R1). Pherin Pharmaceuticals, Inc.; Los Altos, CA: Pherin Report 
MB 007; 1997. 
45. Monti L. Dose dependent effect of pherine PH94B in isolated female human vomeronasal 
organ cells. Pherin Study Report # CL009; Report date: May 18, 1999. 

VistaGen Therapeutics, Inc.
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Protocol PH94B-CL029 
30-Aug-2021 
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46. Monti L, Liebowitz M, Smith M. PH94B: A new intranasal neuroactive steroid with rapid 
onset of anxiolytic activity but a mechanism of action different from benzodiazepines. 
ADAA, 2021. 
47. Lorenz L, Bachem RC, Maercker A. The Adjustment Disorder--New Module 20 as a 
Screening Instrument: Cluster Analysis and Cut-off Values. Int J Occup Environ Med. 
2016;7(4):215-220. 
48. Shevlin M, Hyland P, Ben-Ezra M, Karatzias T, Cloitre M, Vallières F, et al. Measuring 
ICD-11 adjustment disorder: the development and initial validation of the International 
Adjustment Disorder Questionnaire. Acta Psychiatr Scand. 2020;141(3):265-274. 
49. Rickels K, Garcia-Espana F, Mandos LA, Case GW. Physician Withdrawal Checklist 
(PWC-20). J Clin Psychopharmacol. 2008 Aug;28(4):447-51 
50. Bachem R, Perkonigg A, Stein DJ, Maercker A. Measuring the ICD-11 adjustment disorder 
concept: Validity and sensitivity to change of the Adjustment Disorder - New Module 
questionnaire in a clinical intervention study. Int J Methods Psychiatr Res. 2017;26(4). 
 
 

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18. ATTACHMENTS 
18.1. Investigator’s Agreement
PROTOCOL 
NUMBER: 
PH94B-CL029 
PROTOCOL TITLE: 
A Phase 2a Double-blind, Placebo-controlled, Parallel Study of 
PH94B Nasal Spray in the Treatment of Anxiety in Adults with 
Adjustment Disorder with Anxiety 
FINAL PROTOCOL: 
30-Aug-2021 
I have read this protocol and agree to conduct this clinical study as outlined herein. I will ensure 
that all subinvestigators and other study staff members have read and understand all aspects of this 
protocol. I agree to cooperate fully with VistaGen Therapeutics, Inc. and Premier Research during 
the study. I will adhere to all FDA, ICH, and other applicable regulations and guidelines regarding 
clinical studies on an IP during and after study completion. 
Principal Investigator: 
 
Printed Name: 
 
 
 
 
 
 
 
 
 
 
 
 
Signature: 
 
 
 
 
 
 
 
 
 
 
 
Date: 
 
 
 
 
 
 

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APPENDICES
A. Hamilton Anxiety Scale
B. Adjustment Disorder New Module Scale 
C. International Adjustment Disorder Questionnaire 
D. Penn Physician Withdrawal Checklist 
E. Regulations and Good Clinical Practice Guidelines 
 
 

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C. International Adjustment Disorder Questionnaire 
THE INTERNATIONAL ADJUSTMENT DISORDER 
QUESTIONNAIRE (IADQ)
Below is a list of stressful life events that you may have experienced. Please indicate any of the 
following events that are currently applicable to you: 
I am currently experiencing… 
Yes 
1.
Financial problems (e.g., difficulty paying bills, being in debt).
2. Work problems (e.g., unemployment, redundancy, retirement, problems/conflicts 
with colleagues, change of job role). 
 
3. Educational problems (e.g., difficulty with course work, deadline pressure). 
4.
Housing problems (e.g., stressful home move, difficulty finding a secure residence, 
lack of secure residence). 
5. Relationship problems (e.g., break-up, separation or divorce, conflict with family or 
friends, intimacy problems). 
 
6. My own health problems (e.g., illness onset or deterioration, medication issues, 
injury or disability). 
 
7. A loved one’s health problems (e.g., illness onset or deterioration, medication
issues, injury or disability). 
 
8.
Caregiving problems (e.g., emotional stress, time demands).
9. Some other problem not mentioned above. 
 
This section should be completed only if you have answered ‘Yes’ to at least one of the events 
above. The following statements reflect problem that people sometimes experience in relation to 
a stressful life event(s). Thinking about the stressful life event(s) you identified above, please 
indicate how much you have been bothered by each of the following problems in the past 
month:
 
Not at 
all 
A little 
bit 
Moderately
Quite a 
bit
Extremely
10. I worry a lot more since the 
stressful event(s).
 
0
 
1 
 
2 
 
3 
 
4 
11. I can’t stop thinking about the 
stressful event(s).
 
0
 
1 
 
2 
 
3 
 
4 
12. I often feel afraid about what might 
happen in the future since the stressful 
event(s). 
 
0
 
1 
 
2 
 
3 
 
4 
13. I find it difficult to adapt to life since 
the stressful event(s).
 
0
 
1 
 
2 
 
3 
 
4 
14. I find it difficult to relax and feel calm 
since the stressful event(s). 
 
0
 
1 
 
2 
 
3 
 
4 
15. I find it difficult to achieve a state of 
inner peace since the stressful event(s). 
 
0
 
1 
 
2 
 
3 
 
4 
16. Did these problems start within one 
month of the stressful event(s)? 
 
Yes 
 
 
No 

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Not at 
all 
A little 
bit 
Moderately
Quite a 
bit 
Extremely
In the past month have the above problems:
0 
1 
2 
3 
4 
17. Affected your relationships or social life? 
0 
1 
2 
3 
4 
18. Affected your ability to work or 
your educational life? 
 
0 
 
1 
 
2 
 
3 
 
4 
19. Affected any other important part of 
your life? 
 
0 
 
1 
 
2 
 
3 
 
4 
 

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D. Penn Physician Withdrawal Checklist
 
 

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E. Regulations and Good Clinical Practice Guidelines 
1. Regulations 
Refer to the following United States CFR: 
 FDA Regulations 21 CFR, Parts 50.20 – 50.27 
Subpart B – Informed Consent of Human Subjects 
 FDA Regulations 21 CFR, Parts 56.107 – 56.115 
Part 56 – Institutional Review Boards 
Subpart B – Organization and Personnel 
Subpart C – IRB Functions and Operations 
Subpart D – Records and Reports 
 FDA Regulations 21 CFR, Parts 312.50 – 312.70 
Subpart D – Responsibilities of Sponsors and Investigators 
2. Good Clinical Practice Guidelines 
ICH GCP guidelines can be found at the following URLs: 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_G
uideline.pdf 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__
Step_4.pdf