Conditions: Postpartum Depression
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 52
Healthy volunteers: no

Brief summary:
The primary purpose of this study was to evaluate whether the safe-use conditions for administration of brexanolone (ZULRESSO®) can be implemented in a home setting.

Detailed description:

Arms:
arm 1: Participants received a 60-hour single continuous intravenous (IV) infusion of ZULRESSO®, at 30 micrograms per kilogram per hour (mcg/kg/hour) (0 to 4 hours), at 60 mcg/kg/hour (4 to 24 hours), at 90 mcg/kg/hour (24 to 52 hours), followed by a dose taper to 60 mcg/kg/hour (52 to 56 hours), and 30 mcg/kg/hour (56 to 60 hours) during the study.

Interventions: intervention 1: ZULRESSO®
Intervention descriptions: intervention 1: Intravenous infusion of ZULRESSO®.

Protocol document:
Prot_000.pdf: 


 
ASSESSMENT OF SAFE-USE CONDITIONS FOR 
ADMINISTRATION OF ZULRESSO IN A HOME 
SETTING 
PROTOCOL NUMBER: 547-PPD-404 
Investigational Product 
ZULRESSO 
Clinical Phase 
Phase 4 
Sponsor 
Sage Therapeutics, Inc. 
215 First Street 
Cambridge, MA 02142 
Sponsor Contact 
Sage Therapeutics, Inc. 
215 First Street 
Cambridge, MA 02142 
Sponsor Medical Monitor 
, MD 
 
Phone: 
  
 
Date of Original Protocol 
Date of Amendment 1 
27 October 2020 
23 June 2021 
Confidentiality Statement 
The confidential information in this document is provided to you as an investigator or consultant 
for review by you, your staff, and the applicable Institutional Review Board/Independent Ethics 
Committee. Your acceptance of this document constitutes agreement that you will not disclose 
the information contained herein to others without written authorization from Sage Therapeutics, 
Inc. 






Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
4 
INVESTIGATOR’S AGREEMENT 
I have received and read the Investigator’s Brochure for brexanolone injection. I have read the 
547-PPD-404 protocol and agree to conduct the study as outlined. I agree to maintain the 
confidentiality of all information received or developed in connection with this protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
 
Date (DD/MMM/YYYY) 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
5 
CONTACT INFORMATION AND ROLES AND RESPONSIBILITIES OF 
STUDY PERSONNEL 
Table 1: 
Contact Information 
Role in Study 
Name 
Address and Telephone Number 
Sage Study Physician  
, MD, 
 
 
 
Cambridge, MA 02142 
Phone: 
 
SAE reporting 
 
IQVIA Lifecycle Safety (LS)  
4820 Emperor Boulevard 
Durham, NC 27703 
e-mail: Sage.Safety@iqvia.com 
Fax: 1-855-638-1674 
SAE Hotline: 1-855-564-2229  
Product Complaint Contact 
Sage Therapeutics 
e-mail: 
productcomplaints@sagerx.com 
Phone: 1-833-554-7243 
 
Table 2: 
Study Personnel Roles and Responsibilities 
Role 
Key Responsibilities 
Investigator 
Individual responsible for conduct of the clinical study 
Home Infusion Provider 
Company responsible for implementing the safe-use conditions 
for administering ZULRESSO in the home setting and providing, 
overseeing, and training all staff involved in dispensing and 
administering ZULRESSO 
Home Healthcare Provider 
Individual healthcare professional responsible for general care of 
the participant during infusion; present in the participant’s home 
for the duration of study participation; multiple individuals will 
work in shifts to care for the same participant 
Pharmacist or Qualified Designee 
Individual(s) responsible for preparation and dispensing of 
investigational product (IP) and preprogramming the infusion 
pump 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
6 
2. 
SYNOPSIS 
Name of Sponsor/Company: 
Sage Therapeutics, Inc. (hereafter referred to as Sage Therapeutics, or Sage) 
Name of Investigational Product: 
ZULRESSO® 
Name of Active Ingredient: 
brexanolone (previously referred to as SAGE-547) 
Title of Study: 
Assessment of Safe-Use Conditions for Administration of ZULRESSO in a Home Setting 
Number of Sites and Study Location: This is a multicenter study that will take place in the United 
States.  
Phase of Development: Phase 4 
Planned Duration for each Study Participant: 
The total duration of participation may be up to 31 days, including a screening period of up to 
28 days, and a 60-hour infusion of ZULRESSO on Day 1 through Day 3. 
Objectives and Endpoints: 
Primary 
• 
To evaluate whether the safe-use conditions for administration of ZULRESSO can be 
implemented in a home setting 
Secondary 
• 
To identify any process and procedural changes to be implemented for ZULRESSO 
administration at home 
 
 
 
 
Endpoints 
Primary 
• 
Incidence of treatment-emergent adverse events (TEAEs) leading to dose 
interruption/discontinuation 
Secondary 
• 
Incidence of nonadherence with the safe-use conditions for administration of ZULRESSO 
• 
Incidence of use-related issues related to the home administration of ZULRESSO 
• 
Incidence of all TEAEs 
• 
Incidence of medication error  
 
 
 
 
 
 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
7 
 
 
 
 
 
Study Description: 
This is an open-label, multicenter study designed to assess the safe-use conditions for administration 
of ZULRESSO in a home setting to women with postpartum depression (PPD) with the overall goal 
to improve patient access to ZULRESSO treatment. The safety monitoring plan for this study 
incorporates safe-use conditions that are aligned with that of the FDA-approved ZULRESSO Risk 
Evaluation and Mitigation Strategy (REMS) and ZULRESSO prescribing information. A home 
infusion provider is responsible for implementing the safe-use conditions for administering 
ZULRESSO in the home setting. 
This study consists of a screening period of up to 28 days and a 60-hour home infusion of 
ZULRESSO (Days 1 through 3). A home infusion provider will provide, oversee, and train pharmacy 
staff, home healthcare providers, and other home healthcare provider staff involved in dispensing and 
administering ZULRESSO in this study. All investigators and all pharmacy and home healthcare 
provider staff involved in dispensing and administering ZULRESSO will be trained regarding the risk 
of serious harm resulting from excessive sedation and sudden loss of consciousness during the 
administration of ZULRESSO. Home healthcare providers will also counsel participants regarding 
this risk and the importance of reporting any symptoms to a healthcare provider. Use of telehealth by 
the investigator is permitted for screening and remote assessments for monitoring or oversight of 
participants during the ZULRESSO infusion, as required. 
All necessary equipment and supplies (eg, pulse oximeter, body weight scale, etc) used to conduct the 
study will be delivered by a home healthcare provider or shipped to the participant’s home. 
The screening period begins with the informed consent process, which may be conducted 
electronically. Consented participants will undergo remote or in-person screening procedures to 
determine eligibility. 
During the treatment period, a home healthcare provider will arrive at the eligible participant’s home 
on Day 1 to initiate the 60-hour intravenous (IV) infusion of ZULRESSO. The home healthcare 
provider must confirm that the participant continues to meet all of the eligibility criteria and complete 
any predose assessments per Table 3 prior to administering the infusion. 
The open-label 60-hour infusion will be administered as follows: 30 mcg/kg/hour (Hour 0 to 4), then 
60 mcg/kg/hour (Hour 4 to 24), then 90 mcg/kg/hour (Hour 24 to 52), followed by 60 mcg/kg/hour 
(Hour 52 to 56), and 30 mcg/kg/hour (Hour 56 to 60). A programmable peristaltic infusion pump with 
alarm is to be used to ensure accurate delivery of ZULRESSO. The pump will be preprogrammed by 
home infusion provider pharmacy staff. If necessary, the home healthcare provider may reprogram 
the pump in consultation with home infusion provider pharmacy staff for any issues unrelated to 
safety. If the pump must be reprogrammed during the infusion due to safety, the home healthcare 
provider must consult the investigator and if necessary, the pharmacist or qualified designee. 
Due to the risk of excessive sedation and sudden loss of consciousness, for the duration of the 
infusion, participants must be monitored for hypoxia using continuous pulse oximetry equipped with 
an alarm and must be assessed for excessive sedation by a home healthcare provider every 2 hours 
during planned nonsleep periods. At least one home healthcare provider must be continuously 
available on site in the participant’s home for the duration of the ZULRESSO infusion to monitor the 
participant and intervene as necessary. The participant must not be the primary caregiver of her 
dependent(s) and must be accompanied by another adult (other than the home healthcare provider) 
during any interactions with their child(ren) that occur during the infusion. If the participant becomes 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
8 
the primary caregiver of dependent(s) at any point during the infusion, the infusion must be stopped 
and will not be resumed. 
All home healthcare providers will have 24 hour/day access to home infusion nursing and pharmacy 
staff via telephone for any problems with the infusion pump, IV lines, or other equipment 
malfunctions. The investigator will be available 24 hour/day to address protocol -related 
queries/issues in addition to safety-related concerns. 
If excessive sedation or loss of consciousness occur at any time during the infusion, the infusion will 
be stopped until the symptoms resolve. The infusion may be resumed at the same or lower dose as 
deemed clinically appropriate by the investigator. 
The infusion will be immediately stopped if pulse oximetry reveals hypoxia. After an episode of 
hypoxia, the infusion should not be resumed. For any potentially serious adverse reaction, the home 
healthcare provider must assess the participant, administer oxygen in case of hypoxia, and should 
contact local emergency services and the investigator, if warranted. 
A fall precaution protocol must be in place for the duration of the ZULRESSO infusion. 
For lactating participants, the investigator and participant should weigh the developmental and health 
benefits of breastfeeding against any potential adverse effects on the breastfed child from 
ZULRESSO or from the underlying maternal condition. Participants may continue to breastfeed or 
express milk to feed their infant during the infusion if the benefit is deemed to outweigh the risk. 
Participants will also be monitored during the infusion for worsening of depressive symptoms or 
emergent suicidal thoughts and behaviors. 
In addition to local monitoring in the home, oxygen saturation, respiratory rate, blood pressure, and 
heart rate will also be remotely monitored throughout the duration of the infusion using a wearable 
device.  
Compliance to safe-use conditions, processes, and procedures will be assessed by human factors (HF) 
researchers. Throughout the duration of the infusion, home healthcare provider staff will complete 
checklists and/or journals at the end of each day and/or shift to document any use-related issues. Any 
use-related issues determined to be critical in nature will be followed up immediately by an HF team 
member so that the information is recent and can be reported and root caused adequately. 
Upon completion of the infusion, an HF team member will conduct a post-infusion remote interview 
with the home healthcare provider to assess their comprehension of and compliance to processes and 
procedures and to identify potential procedural changes specifically for ZULRESSO administration in 
a home setting, with the goal of further mitigating any use-related issues or errors from occurring in 
the home setting. Situations such as difficulties performing the tasks required to administer the 
infusion, procedural challenges, and unforeseen circumstances (eg, childcare issues, participant 
attempts to drive) will be documented. 
After completing or discontinuing the ZULRESSO infusion, the participants’ level of sedation should 
be assessed. Participants will be cautioned against engaging in potentially hazardous activities 
requiring mental alertness, such as driving, until any sedative effects have dissipated. The home 
healthcare provider who completes the infusion must not leave the participant’s home until she or he, 
in consultation with the investigator as needed, determines that any sedative effects have resolved and 
there are no safety risks to the participant. The home healthcare provider must also ensure that the 
SAE/AESI form(s), if applicable, have been completed and submitted to the investigator prior to 
leaving the participant’s home. 
 
 
 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
9 
 
 
Number of Participants (planned): Up to 50 participants.  
Eligibility Criteria: 
Inclusion Criteria: 
1. Ambulatory female ≥18 years of age 
2. Participant has a current diagnosis of PPD, as confirmed by the investigator 
3. Participant agrees not to be the primary caregiver of any dependents during the infusion and 
must be accompanied by another adult (other than the home healthcare provider) during 
interactions with their child(ren) 
4. Participant has no history of sleep apnea or any clinically significant respiratory conditions 
5. Participant agrees to refrain from the use of central nervous system depressants, such as 
opioids, benzodiazepines, sleep aids and from drinking alcohol during the infusion 
6. Participant is suitable for administration of ZULRESSO in a home setting, as per the 
judgement of the investigator 
7. Participant’s home is suitable and has necessary provisions for administration of ZULRESSO 
and meets the following criteria: 
• 
safe environment for the home infusion provider staff 
• 
access to a working telephone 
• 
electricity and grounded electrical outlets 
• 
running water 
• 
access to back-up emergency services (911 service or ambulance availability) 
• 
sanitary environment 
8. Participant agrees to stay at home until the end-of-study visit has been completed, except for 
a medical emergency 
9. Participant must have a negative pregnancy test at screening and on Day 1 prior to the start of 
the ZULRESSO infusion 
Exclusion criteria: 
1. Participant has end stage renal failure 
2. Participant has known allergy to progesterone or allopregnanolone or any excipients in the 
brexanolone injection 
3. Participant is currently at risk of suicide, as judged by the investigator, or has attempted 
suicide associated with the current episode of PPD 
Investigational Product, Dosage and Mode of Administration: 
ZULRESSO will be administered as a single, continuous, 60-hour IV infusion, administered 
according to the following dose regimen. 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
10 
Time 
point 
Day 1 
0 to 4 hours 
Day 1 
4 to 24 hours 
Day 2-3 
24 to 52 hours 
Day 3 
52 to 56 
hours 
Day 3 
56 to 60 
hours 
Dose 
30 mcg/kg/h 
60 mcg/kg/h 
90 mcg/kg/h a 
60 mcg/kg/h 
30 mcg/kg/h 
a A reduction in dosage to 60 mcg/kg/h may be considered during this time period for participants who do not 
tolerate 90 mcg/kg/h 
Duration of Treatment: 
Each participant will receive a single 60-hour IV infusion of ZULRESSO.  
Statistical Methods: 
A separate statistical analysis plan (SAP) will provide a detailed description of the analyses to be 
performed in the study. The SAP will be finalized and approved prior to database lock. 
General Considerations 
For the purpose of all primary and secondary analyses where applicable, baseline is defined as the last 
measurement prior to initiation of the IP infusion. 
Continuous endpoints will be summarized with number (n), mean, standard deviation, median, 
minimum, and maximum. In addition, change from baseline values will be calculated at each time 
point and summarized descriptively. For categorical endpoints, descriptive summaries will include 
counts and percentages. 
Analysis Sets 
The Safety Set will include all participants administered IP. 
All statistical analyses will be based on summarized data. 
Safety Analysis 
Incidence of TEAEs will be summarized using descriptive statistics. All analysis will be based on the 
Safety Set. 
Sample Size Calculation 
The sample size is based on assuming a 7% incidence rate of TEAEs leading to IP discontinuation or 
interruption, which is the rate observed in the post-marketing setting. With 50 participants who 
receive ZULRESSO, the probability is 0.87 for observing at least 2 events; 0.69 for observing at least 
3 events, and 0.47 for observing at least 4 events. 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
11 
 
 
  
 
Table 3: 
Schedule of Assessments 
 
Screening/ 
Baseline 
(Remote or 
In-person) 
60-Hour 
ZULRESSO 
Home Infusion 
Post-
Infusion/ET 
Study Procedure 
Day -28 to 
Day -1 
Days 1 to 3 
(0 to 60 hours) 
Day 3 
(>60 hours) 
Informed consent 
X 
 
 
Inclusion/exclusion criteria 
X 
X 
(confirm 
participant 
continues to meet 
eligibility criteria 
prior to start of 
infusion) 
 
Demographics/medical and surgical 
history 
X 
 
 
Body weight/height 1 
X 
X 
(prior to start of 
infusion) 
 
Pregnancy test (urine) 
X 
X 
(prior to start of 
infusion) 
 
Participant training by home healthcare 
provider 
 
X 
(prior to start of 
infusion) 
 
Vital signs 2 
 
X 
 
ZULRESSO infusion at home 
 
X 
 
Continuous pulse oximetry (local 
monitoring) 3 
 
X 
 
Remote monitoring of oxygen saturation 
and heart rate via wireless pulse oximeter 
 
X 
 
Monitoring for excessive sedation 
 
X 
(every 2 hours 
during planned 
nonsleep periods) 
 
Daily and/or end-of-shift 
checklist/journal completed by home 
healthcare providers to document any 
use-related issues 
X 
X 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
12 
 
 
  
 
 
Screening/ 
Baseline 
(Remote or 
In-person) 
60-Hour 
ZULRESSO 
Home Infusion 
Post-
Infusion/ET 
Study Procedure 
Day -28 to 
Day -1 
Days 1 to 3 
(0 to 60 hours) 
Day 3 
(>60 hours) 
Post-infusion interview of home 
healthcare provider(s) conducted by HF 
researchers 
 
 
X 
Home healthcare provider to complete 
and submit SAE/AESI form(s), if 
applicable 
 
 
X 
(prior to leaving 
participant’s home) 
Adverse events4 
X 
Prior/concomitant medications4,5 
X 
Abbreviations: BP = blood pressure; ET = early termination; HF = human factors; HR = heart rate; RR = respiratory 
rate. 
Note: Use of telehealth by the investigator is permitted for the screening visit, in addition to remote assessments 
conducted during the ZULRESSO infusion, as required. 
1 After the participant provides informed consent, a body weight scale will be delivered to the participant’s home. 
The participant will weigh herself on the scale approximately 7 days prior to Day 1 and report her body weight to 
study personnel. Body weight at screening/baseline is used to calculate ZULRESSO dose and to be confirmed by 
the home healthcare provider on Day 1 to determine whether any change to ZULRESSO dose is required. Height 
will be collected at Day 1. 
2 Vital signs include BP, RR, HR, and oxygen saturation. o Oxygen saturation, RR, and HR collection will begin 
immediately prior to the start of the infusion and will be monitored continuously through a wearable device. BP 
will be collected prior to the start of the infusion, and all vital signs will be recorded in the event of excessive 
sedation, loss of consciousness, or any other adverse event of special interest.  
3 Oxygen saturation will only be recorded in the event of excessive sedation, loss of consciousness, hypoxia, or 
adverse event of special interest (AESI). 
4 Information regarding diagnosis, isolation, and/or hospitalization due to COVID-19 will be documented as part of 
medical history, AE collection, and prior/concomitant medication/procedure collection at screening and 
throughout the study. 
5 Prior medications will be collected at screening and concomitant medications and/or procedures will be collected 
thereafter. 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
13 
 
 
  
 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
1. 
OPENTITLE PAGE .....................................................................................................1 
2. 
SYNOPSIS ...................................................................................................................6 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............13 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................18 
5. 
INTRODUCTION ......................................................................................................19 
5.1. 
Brexanolone (ZULRESSO®) ......................................................................................19 
5.2. 
Study Rationale ...........................................................................................................19 
5.3. 
Dose Justification ........................................................................................................20 
6. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................21 
6.1. 
Primary Objective .......................................................................................................21 
6.2. 
Secondary Objective ...................................................................................................21 
 
21 
6.4. 
Endpoints ....................................................................................................................21 
6.4.1. 
Primary Endpoint ........................................................................................................21 
6.4.2. 
Secondary Endpoints ..................................................................................................21 
 
21 
7. 
INVESTIGATIONAL PLAN .....................................................................................22 
7.1. 
Overall Study Design ..................................................................................................22 
7.2. 
Number of Participants ...............................................................................................24 
7.3. 
Treatment Assignment ................................................................................................24 
7.4. 
Dose Adjustment Criteria ...........................................................................................24 
7.5. 
Criteria for Study Termination ...................................................................................24 
8. 
SELECTION AND WITHDRAWAL OF PARTICIPANTS .....................................25 
8.1. 
Participant Inclusion Criteria ......................................................................................25 
8.2. 
Participant Exclusion Criteria .....................................................................................25 
8.3. 
Screen Failures ............................................................................................................26 
8.4. 
Investigational Product Discontinuation and Early Termination from the 
Study ...........................................................................................................................26 
8.4.1. 
Investigational Product Discontinuation .....................................................................26 
8.4.2. 
Early Termination from the Study ..............................................................................26 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
14 
 
 
  
 
8.4.3. 
Loss to Follow up .......................................................................................................26 
9. 
TREATMENT OF PARTICIPANTS .........................................................................27 
9.1. 
Description of Investigational Product .......................................................................27 
9.2. 
Prior Medications, Concomitant Medications, Restrictions, and 
Contraception Requirements ......................................................................................27 
9.2.1. 
Prior and Concomitant Medications and/or Supplements ..........................................27 
9.2.2. 
Prohibited Medications ...............................................................................................27 
9.2.3. 
Other Restrictions .......................................................................................................27 
9.3. 
Intervention after the End of the Study .......................................................................27 
9.4. 
Treatment Adherence ..................................................................................................27 
9.5. 
Randomization and Blinding ......................................................................................28 
10. 
INVESTIGATIONAL PRODUCT MATERIALS AND MANAGEMENT .............29 
10.1. 
Investigational Product ...............................................................................................29 
10.2. 
Investigational Product Packaging and Labeling .......................................................29 
10.3. 
Investigational Product Storage ..................................................................................29 
10.4. 
Investigational Product Preparation ............................................................................29 
10.5. 
Investigational Product Administration ......................................................................29 
10.6. 
Investigational Product Accountability, Handling, and Disposal ...............................30 
10.7. 
Product Complaints ....................................................................................................31 
10.8. 
Ancillary Supplies ......................................................................................................31 
11. 
EFFICACY AND CLINICAL PHARMACOLOGY ASSESSMENTS ....................32 
11.1. 
Efficacy Assessments .................................................................................................32 
11.2. 
Clinical Pharmacology Assessments ..........................................................................32 
12. 
SAFETY ASSESSMENTS ........................................................................................33 
12.1. 
Safety Parameters .......................................................................................................33 
12.1.1. 
Demography and Medical History ..............................................................................33 
12.1.2. 
Weight and Height ......................................................................................................33 
12.1.3. 
Vital Signs ..................................................................................................................33 
12.1.4. 
Oxygen Saturation ......................................................................................................33 
12.1.5. 
Remote Monitoring of Oxygen Saturation and Vital Signs ........................................33 
12.1.6. 
Monitoring for Excessive Sedation ............................................................................34 
12.1.7. 
Suicidal Thoughts and Behaviors ...............................................................................34 
12.1.8. 
Pregnancy Screen ........................................................................................................34 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
15 
 
 
  
 
12.1.9. 
Nonadherence with the Safe-use Conditions for Administration of 
ZULRESSO ................................................................................................................34 
12.1.10. 
Daily and/or End-of-Shift Checklist/Journal ..............................................................35 
12.1.11. 
Post-infusion Interview of Home Healthcare Providers .............................................35 
 
 
35 
 
36 
 
36 
 
36 
12.2. 
Adverse and Serious Adverse Events .........................................................................37 
12.2.1. 
Adverse Event Definition ...........................................................................................37 
12.2.2. 
Serious Adverse Event Definition ..............................................................................38 
12.2.3. 
Definition of Adverse Events of Special Interest .......................................................39 
12.2.4. 
Relationship to Investigational Product ......................................................................39 
12.2.5. 
Recording Adverse Events .........................................................................................39 
12.2.6. 
Reporting Serious Adverse Events .............................................................................40 
12.3. 
Pregnancy ...................................................................................................................41 
12.4. 
Overdose .....................................................................................................................41 
12.5. 
Medication Error .........................................................................................................41 
13. 
STATISTICS ..............................................................................................................42 
13.1. 
Data Analysis Sets ......................................................................................................42 
13.2. 
Handling of Missing Data ...........................................................................................42 
13.3. 
General Considerations ...............................................................................................42 
13.4. 
Demographics and Baseline Characteristics ...............................................................42 
13.5. 
Efficacy Analysis ........................................................................................................42 
13.6. 
Safety Analyses ..........................................................................................................42 
13.6.1. 
Adverse Events ...........................................................................................................42 
13.6.2. 
Vital Signs ..................................................................................................................43 
13.6.3. 
Oxygen Saturation ......................................................................................................43 
 
 
43 
13.6.5. 
Nonadherence with Safe-use Administration of ZULRESSO ....................................43 
13.6.6. 
Use-related Issues Related to the Home Administration of ZULRESSO ..................43 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
16 
 
 
  
 
13.6.7. 
Medication Error .........................................................................................................43 
 
 
43 
13.6.9. 
Prior and Concomitant Medications ...........................................................................43 
13.6.10. 
Other Safety Analysis .................................................................................................44 
13.7. 
Clinical Pharmacology Analyses ................................................................................44 
13.8. 
Sample Size and Power ..............................................................................................44 
13.8.1. 
Interim and Data Monitoring Committee Analyses ....................................................44 
14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .........................................45 
14.1. 
Study Monitoring ........................................................................................................45 
14.2. 
Audits and Inspections ................................................................................................45 
14.3. 
Institutional Review Board or Ethics Committee .......................................................45 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................46 
16. 
ETHICS ......................................................................................................................47 
16.1. 
Ethics Review .............................................................................................................47 
16.2. 
Ethical Conduct of the Study ......................................................................................47 
16.3. 
Informed Consent Process ..........................................................................................47 
17. 
DATA HANDLING AND RECORDKEEPING .......................................................49 
17.1. 
Inspection of Records .................................................................................................49 
17.2. 
Retention of Records ..................................................................................................49 
18. 
PUBLICATION POLICY ..........................................................................................50 
19. 
LIST OF REFERENCES ............................................................................................51 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
17 
 
 
  
 
LIST OF TABLES 
Table 1: 
Contact Information ......................................................................................................5 
Table 2: 
Study Personnel Roles and Responsibilities .................................................................5 
Table 3: 
Schedule of Assessments ............................................................................................11 
Table 4: 
Abbreviations and Specialist Terms ...........................................................................18 
Table 5: 
Infusion Rate ...............................................................................................................30 
 
 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
18 
 
 
  
 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 4: 
Abbreviations and Specialist Terms 
Abbreviation 
Definition 
AE 
adverse event 
AESI 
adverse event of special interest 
eCRF 
electronic case report form 
FDA 
Food and Drug Administration 
GABAA  
γ-aminobutyric acid-ligand gated chloride channel 
GCP 
good clinical practice 
HF 
human factors 
ICD-10 
International Classification of Diseases 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IP 
investigational product 
IRB 
Institutional Review Board 
IV 
intravenous 
MedDRA 
Medical Dictionary for Regulatory Activities 
PPD 
postpartum depression 
REMS 
Risk Evaluation and Mitigation Strategies 
SAE 
serious adverse event 
SOP 
standard operating procedure 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
19 
 
 
  
 
5. 
INTRODUCTION 
Postpartum depression (PPD) is a serious mood disorder estimated to affect approximately 
10% to 20% of women giving birth globally. In the United States, estimates of new mothers 
identified with PPD each year vary by state from 10% to 24% with an overall average of 
13.2% (Bauman 2020). PPD is defined in both the International Classification of 
Diseases (ICD)-10 (World Health Organization 2010) and Diagnostic and Statistical Manual of 
Mental Disorders (DSM-5 2013) as a major depressive episode in the postpartum period with 
marked impairment in functioning. PPD often co-occurs with anxiety. PPD is a leading cause of 
maternal mortality (Savitz 2011) and, by affecting maternal functioning, poses serious risks to 
the emotional, cognitive, behavioral, and physical development of the infant and siblings 
(CPS 2004; Noorlander 2008). Findings from several studies implicate that peripartum 
fluctuations in reproductive hormones (in particular, the major progesterone metabolite, 
allopregnanolone) have a pivotal pathophysiological role in PPD (Bloch 2000; Kanes 2017; 
Shule 2014). 
Allopregnanolone is a metabolite of progesterone created by the actions of 5-α reductase and 
3-α hydroxy-steroid dehydrogenase. Allopregnanolone is a potent positive allosteric modulator 
of synaptic and extrasynaptic γ-aminobutyric acid-ligand gated chloride channel (GABAA) 
receptors. Plasma allopregnanolone concentrations rise in concert with progesterone throughout 
pregnancy, reaching the highest physiological concentrations in the third trimester 
(Maguire 2009). After childbirth, these concentrations decrease abruptly (Nappi 2001). Failure of 
GABAA receptors to adapt to these changes at parturition has been postulated to have a role in 
triggering PPD (Maguire 2008). Allopregnanolone and pharmacologically similar compounds 
have been shown to have profound effects on anxiety and depression in animal models 
(Paul 1992; Maguire 2008). 
5.1. 
Brexanolone (ZULRESSO®) 
Brexanolone injection is approved by the US FDA under the trade name ZULRESSO for the 
treatment of PPD in adults. 
The brexanolone drug product is a proprietary formulation of brexanolone drug substance 
(chemically identical to endogenous allopregnanolone) and excipients. 
In clinical studies with ZULRESSO, rapid improvements in depressive symptoms were observed 
by the end of a 60-hour infusion, and these improvements were observed out to 4 weeks beyond 
the end of the infusion. For details on the pharmaceutical properties of brexanolone, and results 
from nonclinical and clinical studies, see the brexanolone Investigator’s Brochure. 
5.2. 
Study Rationale 
In the US, ZULRESSO is available commercially only through a restricted program called the 
ZULRESSO Risk Evaluation and Mitigation Strategy (REMS) due to the risk of serious harm 
resulting from excessive sedation or sudden loss of consciousness during the infusion. The 
requirement for ZULRESSO to be administered only to patients in a medically supervised 
healthcare setting limits patient access to ZULRESSO for the treatment of PPD. There is, 
therefore, a need to increase patient access to ZULRESSO while assuring safe use. Use of 
ZULRESSO in the home setting has the potential to increase patient access to ZULRESSO while 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
20 
 
 
  
 
maintaining the appropriate REMS requirements with elements to assure safe use in the home 
(eg, education of patients and healthcare providers on the risk of excessive sedation and loss of 
consciousness, monitoring of patients for excessive sedation by a healthcare provider, and 
collection of safety data for any events of excessive sedation or loss of consciousness). 
5.3. 
Dose Justification 
The dose for this study is consistent with the recommended dose in the FDA-approved US 
Prescribing Information, which is a continuous 60-hour IV infusion, administered as follows: 
•  0 to 4 hours: Initiate with a dosage of 30 mcg/kg/h  
•  4 to 24 hours: Increase dosage to 60 mcg/kg/h  
•  24 to 52 hours: Increase dosage to 90 mcg/kg/h (a reduction in dosage to 
60 mcg/kg/h may be considered during this time period for participants who do not 
tolerate 90 mcg/kg/h)  
•  52 to 56 hours: Decrease dosage to 60 mcg/kg/h  
•  56 to 60 hours: Decrease dosage to 30 mcg/kg/h 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
21 
 
 
  
 
6. 
STUDY OBJECTIVES AND ENDPOINTS 
6.1. 
Primary Objective 
The primary objective of the study is to evaluate whether the safe-use conditions for 
administration of ZULRESSO can be implemented in a home setting. 
6.2. 
Secondary Objective 
The secondary objective of the study is: 
• To identify any process and procedural changes to be implemented for ZULRESSO 
administration at home 
 
 
 
 
 
 
6.4. 
Endpoints 
6.4.1. 
Primary Endpoint 
• Incidence of treatment-emergent adverse events (TEAEs) leading to dose 
interruption/discontinuation. 
6.4.2. 
Secondary Endpoints 
• Incidence of nonadherence with the safe-use conditions for administration of 
ZULRESSO 
• Incidence of use-related issues related to the home administration of ZULRESSO 
• Incidence of all TEAEs 
• Incidence of medication error  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
22 
 
 
  
 
7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
This is an open-label, multicenter study designed to assess the safe-use conditions for 
administration of ZULRESSO in a home setting to women with PPD with the overall goal to 
improve patient access to ZULRESSO treatment. The safety monitoring plan for this study 
incorporates safe-use conditions that are aligned with that of the FDA-approved ZULRESSO 
REMS and ZULRESSO prescribing information. A home infusion provider is responsible for 
implementing the safe-use conditions for administering ZULRESSO in the home setting. An 
overview of roles and responsibilities of study personnel is provided in Table 2. 
This study consists of a screening period of up to 28 days and a 60-hour home infusion of 
ZULRESSO (Days 1 through 3). A home infusion provider will provide, oversee, and train 
pharmacy staff and home healthcare provider staff involved in dispensing and administering 
ZULRESSO in this study. All investigators and all pharmacy and home healthcare provider staff 
involved in dispensing and administering ZULRESSO will be trained regarding the risk of 
serious harm resulting from excessive sedation and sudden loss of consciousness during the 
administration of ZULRESSO. Home healthcare providers will also counsel participants 
regarding this risk and the importance of reporting any symptoms to a healthcare provider. Use 
of telehealth by the investigator is permitted for screening and remote assessments for 
monitoring or oversight of participants during the ZULRESSO infusion, as required. 
All necessary equipment and supplies (eg, pulse oximeter, body weight scale, etc) used to 
conduct the study will be delivered by a home healthcare provider or shipped to the participant’s 
home. 
The screening period begins with the informed consent process, which may be conducted 
electronically. Consented participants will undergo remote or in-person screening procedures to 
determine eligibility.  
During the treatment period, a home healthcare provider will arrive at the eligible participant’s 
home on Day 1 to initiate the 60-hour intravenous (IV) infusion of ZULRESSO. The home 
healthcare provider must confirm that the participant continues to meet all of the eligibility 
criteria and complete any predose assessments per Table 3 prior to administering the infusion. 
The open-label 60-hour infusion will be administered as follows: 30 mcg/kg/hour (Hour 0 to 4), 
then 60 mcg/kg/hour (Hour 4 to 24), then 90 mcg/kg/hour (Hour 24 to 52), followed by 
60 mcg/kg/hour (Hour 52 to 56), and 30 mcg/kg/hour (Hour 56 to 60). A programmable 
peristaltic infusion pump with alarm is to be used to ensure accurate delivery of ZULRESSO. 
The pump will be preprogrammed by home infusion provider pharmacy staff. If necessary, the 
home healthcare provider may reprogram the pump as described in Section 10.5. 
Due to the risk of excessive sedation and sudden loss of consciousness, for the duration of the 
infusion, participants must be monitored for hypoxia using continuous pulse oximetry equipped 
with an alarm and must be assessed for excessive sedation by a home healthcare provider every 
2 hours during planned nonsleep periods. At least 1 home healthcare provider must be 
continuously available on site in the participant’s home for the duration of the ZULRESSO 
infusion to monitor the participant and intervene as necessary. The participant must not be the 
primary caregiver of her dependent(s) and must be accompanied by another adult (other than the 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
23 
 
 
  
 
home healthcare provider) during any interactions with her child(ren) that occur during the 
infusion. If the participant becomes the primary caregiver of dependent(s) at any point during the 
infusion, the infusion must be stopped and will not be resumed. 
All home healthcare providers will have 24 hours/day access to home infusion nursing and 
pharmacy staff via telephone for any problems with the infusion pump, IV lines, or other 
equipment malfunctions. The investigator will be available 24 hours/day to address 
protocol-related queries/issues in addition to safety-related concerns. 
If excessive sedation or loss of consciousness occur at any time during the infusion, the infusion 
will be stopped until the symptoms resolve. The infusion may be resumed at the same or lower 
dose as deemed clinically appropriate by the investigator. 
The infusion will be immediately stopped if pulse oximetry reveals hypoxia. After an episode of 
hypoxia, the infusion should not be resumed. For any potentially serious adverse reaction, the 
home healthcare provider must assess the participant, administer oxygen in case of hypoxia, and 
should contact local emergency services and the investigator, if warranted. 
A fall precaution protocol must be in place for the duration of the ZULRESSO infusion. 
For lactating participants, the investigator and participant should weigh the developmental and 
health benefits of breastfeeding against any potential adverse effects on the breastfed child from 
ZULRESSO or from the underlying maternal condition. Participants may continue to breastfeed 
or express milk to feed their infant during the infusion if the benefit is deemed to outweigh the 
risk. 
Participants will also be monitored during the infusion for worsening of depressive symptoms or 
emergent suicidal thoughts and behaviors (see Section 12.1.7). 
In addition to local monitoring in the home, oxygen saturation and heart rate will also be 
remotely monitored throughout the duration of the infusion using a wearable device. 
Compliance to safe-use conditions, processes, and procedures will be assessed by human factors 
(HF) researchers through evaluation of daily and/or end-of-shift checklists and/or journals 
completed by home healthcare provider staff (see Section 12.1.10). 
Upon completion of the infusion, an HF team member will conduct a post-infusion remote 
interview with the home healthcare provider to assess their comprehension of and compliance to 
processes and procedures and to identify potential procedural changes specifically for 
ZULRESSO administration in a home setting, with the goal of further mitigating any use-related 
issues or errors from occurring in the home setting (see Section 12.1.11). 
After completing or discontinuing the ZULRESSO infusion, the participants’ level of sedation 
should be assessed. Participants will be cautioned against engaging in potentially hazardous 
activities requiring mental alertness, such as driving, until any sedative effects have dissipated. 
The home healthcare provider who is present when the participant completes the infusion must 
not leave the participant’s home until she or he, in consultation with the investigator as needed, 
determines that any sedative effects have resolved and there are no safety risks to the participant. 
The home healthcare provider must also ensure that the SAE/AESI form(s), if applicable, have 
been completed and submitted to the investigator as described in Section 12.2.3 prior to leaving 
the participant’s home. 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
24 
 
 
  
 
 
 
 
 
 
 
7.2. 
Number of Participants 
Up to 50 participants may participate. 
7.3. 
Treatment Assignment 
In this open-label study, participants will be administered a single, continuous, 60-hour, IV 
infusion of ZULRESSO starting on Day 1. 
7.4. 
Dose Adjustment Criteria 
If excessive sedation occurs at any time during the infusion, the infusion will be stopped until the 
symptoms resolve. The infusion may be resumed at the same or lower dose as clinically 
appropriate. The infusion will be immediately stopped if pulse oximetry reveals hypoxia. After 
an episode of hypoxia, the infusion should not be resumed. 
For participants who do not tolerate the 90 mcg/kg/hour dose for reasons other than hypoxia, a 
reduction to 60 mcg/kg/hour may be considered during the time period that the 90 mcg/kg/hour 
is scheduled to occur. 
Any sedation-related AEs that lead to dose interruption, termination, or reduction should be 
recorded as AESIs, and should be reported in an expedited manner as outlined in Section 12.2.3. 
If other intolerable AEs occur, the infusion will be stopped until the symptoms resolve. The 
infusion may be resumed at the same or lower dose as clinically appropriate. 
7.5. 
Criteria for Study Termination 
Sage Therapeutics may terminate this study or any portion of the study at any time for safety 
reasons, including the occurrence of AEs or other findings suggesting unacceptable risk to 
participants, or for administrative reasons. In the event of study termination, Sage Therapeutics 
will provide written notification to the investigator. Investigational sites must promptly notify 
their IRB/Independent Ethics Committee (IEC), where required, and initiate withdrawal 
procedures for participating participants. 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
25 
 
 
  
 
8. 
SELECTION AND WITHDRAWAL OF PARTICIPANTS 
8.1. 
Participant Inclusion Criteria 
Participants must meet all of the following criteria to qualify for participation in this study: 
1. Ambulatory female ≥18 years of age 
2. Participant has a current diagnosis of PPD, as confirmed by the investigator 
3. Participant agrees not to be the primary caregiver of any dependents during the infusion 
and must be accompanied by another adult (other than the home healthcare provider) 
during interactions with their child(ren) 
4. Participant has no history of sleep apnea or any clinically significant respiratory 
conditions 
5. Participant agrees to refrain from the use of central nervous system depressants, such as 
opioids, benzodiazepines, sleep aids and from drinking alcohol during the infusion 
6. Participant is suitable for administration of ZULRESSO in a home setting, as per the 
judgement of the investigator 
7. Participant’s home is suitable and has necessary provisions for administration of 
ZULRESSO and meets the following criteria: 
• safe environment for the home infusion provider staff 
• access to a working telephone 
• electricity and grounded electrical outlets 
• running water 
• access to back-up emergency services (911 service or ambulance availability) 
• sanitary environment 
8. Participant agrees to stay at home until the end-of-study visit has been completed, except 
for a medical emergency 
9. Participant must have a negative pregnancy test at screening and on Day 1 prior to the 
start of the ZULRESSO infusion 
8.2. 
Participant Exclusion Criteria 
Participants who meet any of the following criteria are disqualified from participation in this 
study: 
1. Participant has end stage renal failure 
2. Participant has known allergy to progesterone or allopregnanolone or any excipients in 
the brexanolone injection 
3. Participant is currently at risk of suicide, as judged by the investigator, or has attempted 
suicide associated with the current episode of PPD 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
26 
 
 
  
 
8.3. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study. A minimal set of screen failure information will be 
collected, including demography, screen failure details, eligibility criteria, and any serious 
adverse event (SAE). 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Rescreened participants should be assigned a new participant number. 
8.4. 
Investigational Product Discontinuation and Early Termination from 
the Study 
A participant may withdraw from the study at any time at his/her own request for any reason. 
The investigator may discontinue a participant from the study and/or from IP for safety, 
behavioral, compliance, or administrative reasons. 
The reason for IP discontinuation and/or the reason for early termination from the study must be 
documented in the participant’s study record and recorded in the participant’s electronic case 
report form (eCRF). 
The investigator must notify the sponsor and/or the medical monitor when a participant stops 
participation in the study for any reason. 
8.4.1. 
Investigational Product Discontinuation 
If it is necessary to discontinue the IP earlier than planned and consent is not withdrawn, 
participants will remain in the study and be followed per protocol to capture assessments for the 
duration of the study period. 
The reason for IP discontinuation must be documented in the participant’s study record and 
recorded in the appropriate eCRF. 
8.4.2. 
Early Termination from the Study 
At the time of study withdrawal/stopping study participation, if possible, the assessments listed 
for the post-infusion visit should be conducted. The participant will be permanently discontinued 
both from the IP and from the study at that time. 
If the participant withdraws consent for disclosure of future information, the sponsor will retain 
and continue to use any data collected before such a withdrawal of consent. 
8.4.3. 
Loss to Follow up 
Not applicable 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
27 
 
 
  
 
9. 
TREATMENT OF PARTICIPANTS 
9.1. 
Description of Investigational Product 
Brexanolone (ZULRESSO) is a sterile, clear, colorless solution that must be diluted prior to 
administration as an IV infusion. ZULRESSO will be administered as a single, continuous, IV 
infusion for 60 hours. Additional details on IP administration are in Section 10.5 and additional 
IP description details can be found in Section 10 and in the brexanolone Investigator’s Brochure. 
9.2. 
Prior Medications, Concomitant Medications, Restrictions, and 
Contraception Requirements 
9.2.1. 
Prior and Concomitant Medications and/or Supplements 
Participants may receive standard of care for patients diagnosed with PPD, including 
psychosocial interventions. Any concomitant medication determined medically necessary for the 
welfare of the participant may be given at the discretion of the investigator at any time during the 
study. 
All medications taken from signing of informed consent through the final study visit (including 
start and end dates, route, dose/units, frequency, and indication) will be recorded on the 
appropriate eCRF. 
9.2.2. 
Prohibited Medications 
Concomitant use of opioids, central nervous system depressants, such as benzodiazepines, or 
other drugs interacting with the GABAA receptor are prohibited in this study as these drugs may 
increase the risk for sedation-like AEs if administered concomitantly with ZULRESSO. 
9.2.3. 
Other Restrictions 
The participant should not engage in potentially hazardous activities requiring mental alertness 
and should not drive a car until after completion of the ZULRESSO infusion and until any 
feelings of sedation have dissipated. The participant must not leave her house for the duration of 
the infusion except in the case of a medical emergency. The participant must be accompanied 
during interactions with her child(ren) by at least 1 adult (other than the home healthcare 
provider) for the duration of the infusion. 
Alcohol consumption while receiving ZULRESSO is prohibited. 
IV medications may not be coadministered with ZULRESSO in the same infusion line. 
9.3. 
Intervention after the End of the Study 
Not applicable 
9.4. 
Treatment Adherence 
IP will be administered to participants by home healthcare provider staff, as described in 
Section 10.5. The designated staff will record the time and dose of IP administration in the 
source documents. Any reasons for nonadherence will also be documented. Deviation(s) from 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
28 
 
 
  
 
the prescribed dosage regimen will be documented. Details on IP accountability are included in 
Section 10.6. 
9.5. 
Randomization and Blinding 
This is an open-label study in which all participants will receive ZULRESSO. 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
29 
 
 
  
 
10. 
INVESTIGATIONAL PRODUCT MATERIALS AND 
MANAGEMENT 
10.1. 
Investigational Product 
Brexanolone (ZULRESSO) is a sterile, clear, colorless, and preservative-free solution. It is 
hypertonic and must be diluted prior to administration as an IV infusion. Each mL of solution 
contains 5 mg of brexanolone, 250 mg of betadex sulfobutyl ether sodium as a solubilizer, citric 
acid and sodium citrate as buffering agents, and Water for Injection, USP. Hydrochloric acid or 
sodium hydroxide may be used during manufacturing to adjust pH. 
10.2. 
Investigational Product Packaging and Labeling 
IP will be provided to the home infusion provider. 
The IP is sterile-filtered and aseptically filled into 20-mL clear glass vials with a stopper 
container closure system. IP is intended to be used as a single-use vial. 
IP labels with all required information and conforming to all applicable FDA Code of Federal 
Regulations and Good Manufacturing Practices/Good Clinical Practices (GCP) guidelines will be 
prepared by the sponsor. 
Additional information regarding the packaging and labeling is provided in the pharmacy 
manual. 
10.3. 
Investigational Product Storage 
IP vials should be stored under refrigerated conditions (2 to 8°C) and suitably protected from 
light. The vials must be carefully stored safely and separately from other drugs. The IP may not 
be used for any purpose other than the present study. 
Once the admixture in IV bags is dispensed to the participant’s home, the IV bags should be 
stored under refrigerated conditions. IV bags may be stored refrigerated for up to 96 hours after 
they are admixed. 
Additional information regarding IP storage is provided in the brexanolone Investigator’s 
Brochure. 
10.4. 
Investigational Product Preparation 
The home infusion provider pharmacist or qualified designee will be responsible for preparing IP 
for dosing. 
Refer to the pharmacy manual for specific instructions regarding requirements for IV bags and 
labeling, infusion sets, infusion preparation and administration instructions. 
10.5. 
Investigational Product Administration 
IP will be administered as a single, continuous, IV infusion for 60 hours, by a home healthcare 
provider in the participant’s home. The prepared admixture will be administered at room 
temperature. 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
30 
 
 
  
 
The specific infusion dose of IP will be calculated based on weight (obtained at screening and 
verified on Day 1 prior to the start of the infusion) for each participant and will be administered 
according to the dose regimen in Table 5. 
Table 5: 
Infusion Rate 
Time point 
Day 1 
0 to 4 hours 
Day 1 
4 to 24 hours 
Day 2 to 3 
24 to 52 hours 
Day 3 
52 to 56 hours 
Day 3 
56 to 60 hours 
Dose 
30 mcg/kg/h 
60 mcg/kg/h 
90 mcg/kg/h 
60 mcg/kg/h 
30 mcg/kg/h 
The dose regimen will be preprogrammed into the infusion pump by the pharmacist or qualified 
designee. If necessary, the home healthcare provider may reprogram the pump in consultation 
with the home infusion provider pharmacy staff for any issues unrelated to safety. If the pump 
must be reprogrammed during the infusion due to safety, the home healthcare provider must 
consult the investigator and if necessary, the pharmacist or qualified designee. 
Dosing should begin in the morning (on Day 1) to allow for recognition of excessive sedation 
during planned nonsleep periods when the dose increases to 60 mcg/kg/hour and subsequently to 
90 mcg/kg/hour. 
Dose adjustments are permitted as described in Section 7.4. 
Administration of prepared IV bags at room temperature should not exceed 12 hours (ie, IV bags 
should be changed at least every 12 hours). 
Refer to the pharmacy manual for complete details on preparation and administration. 
10.6. 
Investigational Product Accountability, Handling, and Disposal 
Upon receipt of IP (vials), the responsible pharmacist or qualified designee, will inspect the IP 
and complete and follow the instructions regarding receipt and storage in the Investigator’s 
Brochure and (where applicable) in the pharmacy manual. A copy of the shipping documentation 
will be kept in the study files. 
The pharmacist or qualified designee will ship the prepared infusion bags and ancillary supplies 
(see Section 10.8) to the participant’s home. Participants will be instructed not to open 
shipments. Upon arrival at the participant’s home on Day 1, the home healthcare provider will be 
responsible for opening and assessing the shipped supplies. 
The home healthcare provider should check the prepared infusion bags and ancillary supplies 
and verify proper identity, quantity, integrity, and temperature conditions, and report any 
deviations, dispensing errors, or discrepancies to the sponsor, the investigator, and the home 
infusion provider immediately. 
The home healthcare provider will access the telemedicine platform upon arrival to the 
participant’s home prior to initiation of the IP infusion. Via the telemedicine platform, the home 
healthcare provider will provide the necessary participant-identifying information, including the 
participant identification number assigned at screening, and obtain the medication identification 
number for the IP to be dispensed and the weight-based dosing information for that participant. 
The medication ID number that was received at the participant’s home must be recorded. 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
31 
 
 
  
 
The IP provided is for use only as directed in this protocol. The investigator, pharmacist or 
qualified designee, and other home infusion provider staff involved in dispensing and 
administering the IP infusion must keep a record of all IP and ancillary supplies (see 
Section 10.8) received, used, and returned/discarded. 
Sage Therapeutics will be permitted access to the study supplies at any time with appropriate 
notice during or after completion of the study to perform drug accountability reconciliation. 
The investigator, pharmacist or qualified designee, and other home infusion provider staff are 
responsible for IP and ancillary supply accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
At the end of the infusion for each participant, all used and unused IV bags will be returned to 
the home infusion provider for destruction per the home infusion provider’s procedures; 
disposition of IP will be documented. IP may not be destroyed until accountability and 
reconciliation procedures have been completed. 
10.7. 
Product Complaints 
A product complaint is any written, electronic, or verbal expression of dissatisfaction regarding 
the identity, quality, reliability, safety, purity, potency, effectiveness, or performance (applicable 
for approved marketed products) of a drug product after it is released for distribution. 
In the course of conduct of the study, study personnel may become aware of a product complaint 
associated with the use of a Sage product. Personnel shall notify Sage within 24 hours by 
forwarding the product complaint information via the contact information listed in Table 1 and in 
the pharmacy manual. Where possible, personnel should segregate and retain any product, 
materials, or packaging associated with the product complaint until further instruction is 
provided by Sage or its designated representative(s). 
10.8. 
Ancillary Supplies 
The home infusion provider will provide PVC, non-DEHP, nonlatex infusion sets and a 
programmable peristaltic infusion pump with alarm for each participant. The pharmacist or 
qualified designee will ship the infusion sets and preprogrammed infusion pump to the 
participant’s home prior to Day 1. At the end of the infusion for each participant, the infusion 
set(s) and pump will be returned to the home infusion provider per the home infusion provider’s 
procedures; disposition of ancillary supplies will be documented. 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
32 
 
 
  
 
11. 
EFFICACY AND CLINICAL PHARMACOLOGY ASSESSMENTS 
11.1. 
Efficacy Assessments 
Not applicable 
11.2. 
Clinical Pharmacology Assessments 
Not applicable 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
33 
 
 
  
 
12. 
SAFETY ASSESSMENTS 
12.1. 
Safety Parameters 
All assessments will be recorded at the time points summarized in the Schedule of Assessments 
(Table 3). 
12.1.1. 
Demography and Medical History 
Demographic characteristics (age, race, sex, ethnicity) and a full medical and surgical history 
will be documented. 
Information regarding diagnosis, isolation, and/or hospitalization due to COVID-19 will be 
documented as part of medical history, AE collection, and prior/concomitant 
medication/procedure collection at screening and throughout the study. 
12.1.2. 
Weight and Height  
After the participant provides informed consent, a body weight scale will be delivered to the 
participant’s home. The participant will weigh herself on the scale approximately 7 days prior to 
Day 1 and report her body weight to study personnel. Body weight at screening/baseline is used 
to calculate ZULRESSO dose and is to be confirmed by the home healthcare provider on Day 1 
prior to dosing to determine whether any change to ZULRESSO dose is required. 
12.1.3. 
Vital Signs 
Vital signs include blood pressure, respiratory rate, heart rate, and oxygen saturation. Blood 
pressure should be collected in the supine position at all scheduled time points. Respiratory rate, 
heart rate, and oxygen saturation will be monitored continuously through a wearable device. The 
wearable device may also track additional patient parameters such as body temperature and step 
count that will not be collected in the telemedicine platform or study database.  
Additionally, vital signs should be collected for any participant who experiences an AESI 
(defined in Section 12.2.3) as soon as is feasible after the onset of the event and recorded as 
unscheduled in the eCRF. Collection of vital signs should occur per local clinical practice, at a 
minimum until the participant is considered to have recovered from the event.  
12.1.4. 
Oxygen Saturation 
Participants will be monitored for hypoxia using continuous pulse oximetry equipped with an 
alarm. Oxygen saturation will only be recorded in the event of excessive sedation, loss of 
consciousness, hypoxia, or AESI. The infusion will be immediately stopped if pulse oximetry 
reveals hypoxia. After an episode of hypoxia, the infusion should not be resumed. 
For any potentially serious adverse reaction, the home healthcare provider must assess the 
participant and administer oxygen in case of hypoxia and should contact local emergency 
services and the investigator, if warranted. 
12.1.5. 
Remote Monitoring of Oxygen Saturation and Vital Signs 
In addition to local monitoring in the home, oxygen saturation and vital signs will also be 
remotely monitored continuously throughout the duration of the infusion using a wireless, 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
34 
 
 
  
 
 
 
 
 
12.1.6. 
Monitoring for Excessive Sedation 
For the duration of the infusion, participants must be assessed for excessive sedation by a 
healthcare provider every 2 hours during planned nonsleep periods. If excessive sedation occurs 
at any time during the infusion, the infusion will be stopped until the symptoms resolve. The 
infusion may be resumed at the same or lower dose as clinically appropriate (see Section 7.4), 
and an AESI is to be reported (see Section 12.2.3). 
For any potentially serious adverse reaction, the home healthcare provider must assess the 
participant and should contact local emergency services and the investigator, if warranted. 
12.1.7. 
Suicidal Thoughts and Behaviors 
Participants should be counseled before the start of the ZULRESSO infusion to pay close 
attention to any changes related to suicidal thoughts or behaviors, especially sudden changes in 
mood, behavior, thoughts, or feelings; participants should tell the healthcare provider right away 
if she has any new or sudden changes in mood, behavior, thoughts, or feelings. 
The investigator should consider changing the therapeutic regimen, including discontinuing 
ZULRESSO, in participants whose depression becomes worse or who experience emergent 
suicidal thoughts and behaviors. 
12.1.8. 
Pregnancy Screen 
A urine pregnancy test will be conducted for all participants at screening; a urine pregnancy test 
will be conducted on Day 1 prior to the start of the infusion. 
12.1.9. 
Nonadherence with the Safe-use Conditions for Administration of ZULRESSO 
A secondary endpoint of this study is incidence of nonadherence with the safe-use conditions for 
administration of ZULRESSO. Nonadherence with safe-use conditions for administration of 
ZULRESSO in the home setting is defined by any of the following: 
• Failure of the home infusion provider to train all pharmacy and home healthcare 
provider staff involved in dispensing and administration of ZULRESSO on risk of 
excessive sedation and loss of consciousness 
• Failure of home healthcare providers to counsel participants on risk of excessive 
sedation and loss of consciousness 
• Failure of home infusion provider to deliver ZULRESSO as per protocol 
requirements 
• Failure to provide preprogrammed peristaltic pump with alarm 
• Failure by the home healthcare provider to assess for excessive sedation every 
2 hours during planned nonsleep periods 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
35 
 
 
  
 
• Failure to have at least one home healthcare provider continuously available on site in 
the participant’s home for the duration of the ZULRESSO infusion 
• Failure to have fall protocol in place 
• Failure to continuously monitor participants with pulse oximeter with alarm 
• Failure to stop infusion when participant is primary caregiver of dependents 
• Failure by the home healthcare provider to change the infusion bag according to the 
protocol 
• Failure to stop the infusion upon identification of excessive sedation, loss of 
consciousness, or hypoxic episode 
• Infusion resumed after an episode of hypoxia 
• Failure to caution participants post-infusion against engaging in potentially hazardous 
activities requiring mental alertness, such as driving, until any sedative effects have 
dissipated 
• Failure to complete the AESI/SAE form(s), as applicable 
12.1.10. 
Daily and/or End-of-Shift Checklist/Journal 
Throughout the duration of the infusion, home healthcare provider staff will complete checklists 
and/or journals at the end of each day and/or shift to document any use-related issues, including 
how the issues were addressed and followed-up. Any use-related issues determined to be critical 
in nature will be followed up immediately by a remote HF team member so that the information 
is recent and can be reported adequately and analyzed for root causes. This also includes 
nonadherence issues in relation to safe-use conditions for administration of ZULRESSO as 
described in Section 12.1.9. 
12.1.11. 
Post-infusion Interview of Home Healthcare Providers 
An HF team member will conduct a post-infusion remote interview (no more than 3 days after 
completion of the infusion) with the home healthcare provider to assess their comprehension of 
and compliance to processes and procedures and to identify potential procedural changes 
specifically for ZULRESSO administration in a home setting. Situations such as difficulties 
performing the tasks required to administer the infusion, procedural challenges, and unforeseen 
circumstances (eg, childcare issues, participant attempts to drive) will be documented. 
 
 
 
 
 
 
 
 
 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
36 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
37 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12.2. 
Adverse and Serious Adverse Events 
12.2.1. 
Adverse Event Definition 
An AE is any untoward medical occurrence in a patient or clinical investigation participant 
administered a pharmaceutical product and 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), symptom or disease temporally associated with the use of a 
medicinal (investigational) product whether or not related to the medicinal (investigational) 
product. In clinical studies, an AE can include an undesirable medical condition occurring at any 
time, including baseline or washout periods, even if no study treatment has been administered. 
A TEAE is defined as an adverse event with onset after the start of IP, or any worsening of a pre-
existing medical condition/adverse event with onset after the start of IP and throughout the study. 
The term IP includes any Sage IP, a comparator, or a placebo administered in a clinical study. 
Laboratory abnormalities and changes from baseline in vital signs, and ECGs are considered AEs 
if they result in discontinuation or interruption of study treatment, require therapeutic medical 
intervention, meet protocol specific criteria (if applicable) or if the investigator considers them to 
be clinically significant. Any abnormalities that meet the criteria for a serious adverse event 
(SAE) should be reported in an expedited manner (see Section 12.2.6). Laboratory abnormalities 
and changes from baseline in vital signs and ECGs that are clearly attributable to another AE do 
not require discrete reporting (eg, electrolyte disturbances in the context of dehydration, 
chemistry and hematologic disturbances in the context of sepsis). 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
38 
 
 
  
 
All AEs that occur after any participant has signed the informed consent and throughout the 
duration of the study, whether or not they are related to the study, must be reported to Sage 
Therapeutics. 
Participants who discontinue the IP due to an AE, regardless of investigator-determined 
causality, should be followed until the event is resolved, considered stable, or the investigator 
determines the event is no longer clinically significant. Any AEs that are unresolved at the 
participant’s last AE assessment in the study are followed up by the investigator for as long as 
medically indicated, but without further recording in the eCRF (which includes the telemedicine 
platform). The sponsor or its representative retains the right to request additional information for 
any patient with ongoing AE(s)/SAE(s) at the end of the study, if judged necessary. 
12.2.2. 
Serious Adverse Event Definition 
An SAE is any untoward medical occurrence that at any dose: 
• Results in death 
• Places the participant at immediate risk of death (a life-threatening event); however, 
this does not include an event that, had it occurred in a more severe form, might have 
caused death 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability or incapacity 
• Results in a congenital abnormality or birth defect 
An SAE may also be any other medically important event that, in the opinion of the investigator 
may jeopardize the participant or may require medical intervention to prevent one of the 
outcomes listed above (examples of such events include allergic bronchospasm requiring 
intensive treatment in an emergency room or convulsions occurring at home that do not require 
an inpatient hospitalization). 
All SAEs that occur after any participant has signed the ICF and throughout the duration of the 
study, whether or not they are related to the study, must be recorded on the SAE/AESI report 
form provided by Sage Therapeutics. Any SAE that is ongoing when the participant completes 
their final study visit, will be followed by the investigator until the event has resolved, stabilized, 
returned to baseline status, or until the participant dies or is lost to follow up. 
A prescheduled or elective procedure or routinely scheduled treatment will not be considered an 
SAE, even if the participant is hospitalized. The site must document all of the following: 
• The prescheduled or elective procedure or routinely scheduled treatment was 
scheduled (or on a waiting list to be scheduled) prior to obtaining the participant’s 
consent to participate in the study. 
• The condition requiring the prescheduled or elective procedure or routinely scheduled 
treatment was present before and did not worsen or progress, in the opinion of an 
Investigator, between the participant’s consent to participate in the study and at the 
time of the procedure or treatment. 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
39 
 
 
  
 
12.2.3. 
Definition of Adverse Events of Special Interest 
An AESI is an AE/SAE of scientific and/or medical concern, specific to the product or program 
for which ongoing monitoring and rapid communication by the investigator to the sponsor is 
required. Such adverse events normally require thorough documentation and investigation in 
order to characterize them. 
The following events are considered AESIs and should be reported on the SAE/AESI form 
within 72 hours. 
• Excessive sedation 
• Loss of consciousness 
• Any sedation-related AE that leads to dose reduction, interruption, or termination 
If the AESI also qualifies as an SAE, the SAE/AESI form should be submitted per the guidelines 
per Section 12.2.6. At the end of the ZULRESSO infusion, the home healthcare provider must 
ensure the SAE/AESI form(s), if applicable, have been submitted prior to leaving the 
participant’s home. 
12.2.4. 
Relationship to Investigational Product 
The investigator must make the determination of relationship to the IP for each adverse event 
(not related, related). The following definitions should be considered when evaluating the 
relationship of AEs and SAEs to the IP. 
Not Related 
An AE will be considered “not related” to the use of the IP if there is not a reasonable 
possibility that the event has been caused by the IP. Factors pointing towards this 
assessment include but are not limited to: the lack of temporal relationship between 
administration of the IP and the event, the presence of biologically implausible 
relationship between the product and the AE, or the presence of a more likely 
alternative explanation for the AE 
Related 
An AE will be considered “related” to the use of the IP if there is a reasonable 
possibility that the event may have been caused by the product under investigation. 
Factors that point towards this assessment include but are not limited to: a positive 
rechallenge, a reasonable temporal sequence between administration of the drug and 
the event, a known response pattern of the suspected drug, improvement following 
discontinuation or dose reduction, a biologically plausible relationship between the 
drug and the AE, or a lack of alternative explanation for the AE 
12.2.5. 
Recording Adverse Events 
Adverse events spontaneously reported by the participant and/or in response to an open question 
from the study personnel or revealed by observation will be recorded during the study. The AE 
term should be reported in standard medical terminology when possible. For each AE, the 
investigator will evaluate and report the onset (date and time), resolution (date and time), 
intensity, causality, action taken, outcome and seriousness (if applicable), and whether the AE 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
40 
 
 
  
 
resulted in IP dose reduction or interruption, discontinuation of the IP, or withdrawal from the 
study. 
Intensity will be assessed according to the following scale: 
• Mild: symptom(s) barely noticeable to participant or does not make participant 
uncomfortable; does not influence performance or functioning; prescription drug not 
ordinarily needed for relief of symptom(s) 
• Moderate: symptom(s) of a sufficient severity to make participant uncomfortable; 
performance of daily activity is influenced; participant is able to continue in study; 
treatment for symptom(s) may be needed 
• Severe: symptom(s) cause severe discomfort; symptoms cause incapacitation or 
significant impact on participant’s daily life; severity may cause cessation of 
treatment with IP; treatment for symptom(s) may be given and/or participant 
hospitalized 
It is important to distinguish between serious and severe AEs. Severity is a measure of intensity 
whereas seriousness is defined by the criteria under Section 12.2.2. An AE of severe intensity 
may not necessarily be considered serious. 
12.2.6. 
Reporting Serious Adverse Events 
In order to adhere to all applicable laws and regulations for reporting an SAE(s), the investigator 
must notify Sage or designee within 24 hours of the study site staff becoming aware of the 
SAE(s). The investigator must complete, sign and date the SAE report form, verify the accuracy 
of the information recorded on the SAE report form with the corresponding source documents, 
and send a copy to Sage or designee. 
Additional follow-up information, if required or available, should all be sent to Sage or designee 
within 24 hours of receipt on a follow-up SAE report form and placed with the original SAE 
information and kept with the appropriate section of the eCRF and/or study file. 
Serious adverse events occurring after the designated follow-up time for the study, should be 
reported to Sage or designee according to the timelines noted above only if the investigator 
considers the SAE related to IP. 
Sage, or designee, is responsible for notifying the relevant regulatory authorities of certain 
events. It is the Principal Investigator’s responsibility to notify the IRB/IEC of all SAEs that 
occur in participants who are under his or her oversight. Investigators will also be notified of all 
suspected unexpected serious adverse reactions (SUSARs) that occur during the clinical study. 
IRBs/IECs will be notified of SAEs and/or SUSARs as required by local law. 
In addition, appropriate personnel in Sage Drug Safety and Pharmacovigilance or designee will 
unblind SUSARs for the purpose of regulatory reporting. Sage or designee will submit SUSARs 
(in blinded or unblinded fashion) to regulatory agencies according to local law. Sage, or 
designee, will submit SUSARS to Investigators in a blinded fashion. 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
41 
 
 
  
 
12.3. 
Pregnancy 
Based on findings from animal studies of other drugs that enhance GABAergic inhibition, 
ZULRESSO may cause fetal harm. If a participant becomes pregnant after the first 
administration of IP, pregnancy information must be collected and recorded on the Pregnancy 
Form and submitted to the sponsor within 24 hours of learning of the pregnancy. Details will be 
collected for all pregnancies for which conception was likely to have occurred after the start of 
IP administration until 5 terminal half-lives following the last administration of IP or until the 
completion of the study whichever is longer. Any pregnancy occurring in that time frame will be 
followed until delivery or termination of the pregnancy.  
The participant will be followed to determine the outcome of the pregnancy. The outcome of all 
pregnancies (eg, spontaneous abortion, elective abortion, normal birth) must be followed and 
documented even if the participant was discontinued from the study. The investigator will collect 
follow-up information on the participant and the neonate, and the information will be forwarded 
to Sage or designee. Generally, follow up will not be required for longer than 6 to 8 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, regardless of 
fetal status (presence or absence of anomalies) or indication for the procedure. 
Pregnancy in itself is not regarded as an AE unless there is a suspicion that an IP may have 
interfered with the effectiveness of a contraceptive medication. Any complication during 
pregnancy (eg, anemia, infections, pre-eclampsia) should be reported as an AE/SAE. If the 
outcome of the pregnancy meets the criteria for immediate classification as an SAE (ie, 
spontaneous abortion, stillbirth, neonatal death,), the investigator should follow the procedures 
for reporting an SAE. 
12.4. 
Overdose 
Overdoses in the absence of clinical signs and symptoms should not be recorded as a separate 
AE on the eCRF; however, all overdoses must be recorded on an Overdose form and sent to Sage 
or designee within 24 hours of the site becoming aware of the overdose. An overdose must be 
reported to Sage or designee even if the overdose does not result in an AE. If an overdose results 
in an AE, the AE must be recorded. 
12.5. 
Medication Error 
Medication error is any preventable event that may cause or lead to inappropriate medication use 
or patient harm while the medication is in the control of the healthcare professional, patient, or 
consumer. All medication errors must be recorded and sent to Sage or designee within 24 hours 
of the site becoming aware of the medication error. The medication error must be reported to 
Sage or designee even if the medication error does not result in an AE. If a medication error 
results in an AE, the AE must be recorded and reported as described in Section 12.2. 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
42 
 
 
  
 
13. 
STATISTICS 
Detailed description of the analyses to be performed in the study will be provided in the 
statistical analysis plan (SAP). The SAP will be finalized and approved prior to database lock. 
Any changes/additions to the SAP following database lock will be described in detail in the 
clinical study report. 
13.1. 
Data Analysis Sets 
The Safety Set will include all participants administered ZULRESSO. 
13.2. 
Handling of Missing Data 
Every attempt will be made to avoid missing data. All participants will be used in the analyses, 
as per the analysis populations, using all nonmissing data available. No imputation process will 
be used to estimate missing data. 
13.3. 
General Considerations 
For the purpose of all primary and secondary analyses where applicable, baseline is defined as 
the last measurement prior to initiation of the ZULRESSO infusion. 
Continuous endpoints will be summarized with number (n), mean, standard deviation, median, 
minimum, and maximum. In addition, change from baseline values will be calculated at each 
time point and summarized descriptively. For categorical endpoints, descriptive summaries will 
include counts and percentages. 
13.4. 
Demographics and Baseline Characteristics 
Demographic data, such as age, race, and ethnicity, and baseline characteristics (eg, weight), will 
be summarized using the Safety Set. 
Pregnancy test results will be listed but not summarized. 
Medical history will be listed by participant. 
13.5. 
Efficacy Analysis 
Not applicable 
13.6. 
Safety Analyses 
Safety data collected in this study (ie, AEs, concomitant medication usage, changes from 
baseline in vital signs, nonadherence with safe-use conditions with administration of 
ZULRESSO, and 
) will be listed 
by participant and summarized. All safety summaries will be performed on the Safety Set using 
treatment received. 
13.6.1. 
Adverse Events 
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA) 
Version 24.0 or higher. A TEAE is defined as an AE with onset after the start of IP. The analysis 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
43 
 
 
  
 
of AEs will be based on the concept of TEAEs. The incidence of TEAEs will be summarized by 
System Organ Class (SOC) and preferred term. In addition, summaries will be provided by 
intensity (mild, moderate, severe) and by causality (related, not related) to IP. 
Any TEAEs leading to IP discontinuation, dose reduction or interruption, or study withdrawal 
and any treatment-emergent SAEs and AESIs will be summarized. 
All AEs, SAEs, and AESIs (including those with onset or worsening before the start of IP) 
through the end of the study will be listed. 
13.6.2. 
Vital Signs 
Vital sign results at each visit and mean changes from baseline will be summarized by scheduled 
visit. Potentially clinically significant values will be summarized. Vital sign results will be listed 
by participant and timing of collection. 
13.6.3. 
Oxygen Saturation 
Oxygen saturation results at baseline and results recorded for any event of excessive sedation, 
loss of consciousness, hypoxia or AESI, if applicable, will be summarized. Oxygen saturation 
results, if applicable, will be listed by participant and timing of collection. 
 
 
 
 
13.6.5. 
Nonadherence with Safe-use Administration of ZULRESSO 
The incidence of nonadherence with safe-use administration of ZULRESSO will be summarized. 
13.6.6. 
Use-related Issues Related to the Home Administration of ZULRESSO 
Use-related issues of ZULRESSO will be summarized. 
13.6.7. 
Medication Error  
The incidence of medication error will be summarized.  
 
 
 
 
 
 
13.6.9. 
Prior and Concomitant Medications 
Medications will be recorded throughout the duration of the study and may be coded using 
World Health Organization-Drug dictionary Global B3 March 2020, or later. 
Medications taken prior to the initiation of the start of IP will be denoted “Prior”. Those 
medications taken prior to the initiation of the IP and continuing beyond the initiation of the IP 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
44 
 
 
  
 
or those medications started at the same time or after the initiation of the IP will be denoted 
“Concomitant”. 
Medications will be presented according to whether they are “Prior” or “Concomitant” as 
defined above. If medication dates are incomplete and it is not clear whether the medication was 
concomitant, it will be assumed to be concomitant. 
Details of prior and concomitant medications will be listed by participant, start date, and 
verbatim term. 
13.6.10. 
Other Safety Analysis 
Analysis of use-related issues and home healthcare provider comprehension of and compliance 
to processes and procedures will be described in the SAP. 
13.7. 
Clinical Pharmacology Analyses 
Not applicable. 
13.8. 
Sample Size and Power 
The sample size is based on assuming a 7% incidence rate of TEAEs leading to IP 
discontinuation or interruption, which is the rate observed in the post-marketing setting. With 
50 participants who receive ZULRESSO, the probability is 0.87 for observing at least 2 events; 
0.69 for observing at least 3 events, and 0.47 for observing at least 4 events. 
13.8.1. 
Interim and Data Monitoring Committee Analyses 
Not applicable. 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
45 
 
 
  
 
14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
14.1. 
Study Monitoring 
Before an investigational site can enter a participant into the study, a representative of Sage 
Therapeutics will remotely assess the investigational study site per Sage SOPs to determine 
suitability of the investigator to oversee the clinical study and discuss with the investigator(s) and 
other personnel their responsibilities with regard to protocol adherence, and the responsibilities 
of Sage Therapeutics or its representatives. This will be documented in a Clinical Trial 
Agreement between Sage Therapeutics and the investigator. 
During the study, a monitor from Sage Therapeutics or representative will have regular contacts 
with the investigational site, for the following: 
• Provide information and support to the investigator(s) 
• Confirm that the investigational team is adhering to the protocol, and that data are being 
accurately recorded 
• Remotely review electronic source data collected through the telemedicine platform and 
review any participant medical records, and other records relevant to the study. This will 
require direct access to all original records for each participant (eg, clinic charts). 
• Record and report any protocol deviations not previously sent to Sage Therapeutics. 
• Confirm AEs and SAEs have been properly documented in the telemedicine platform and 
confirm any AESIs or SAEs have been forwarded to Sage Therapeutics and those SAEs 
that met criteria for reporting have been forwarded to the IRB or IEC. 
14.2. 
Audits and Inspections 
Sage Therapeutics or authorized representatives of Sage Therapeutics, a regulatory authority, or 
an IEC or an IRB may visit the site to perform an audit(s) or inspection(s). The purpose of a Sage 
Therapeutics audit or a regulatory authority inspection is to systematically and independently 
examine all study-related activities and documents to determine whether these activities were 
conducted, and data were recorded, analyzed, and accurately reported according to the protocol, 
GCP/ICH GCP guidelines, and any applicable regulatory requirements. The investigator should 
contact Sage Therapeutics immediately if contacted by a regulatory agency or IRB/IEC about an 
inspection. 
14.3. 
Institutional Review Board or Ethics Committee 
The Principal Investigator must obtain IRB (or IEC) approval for the clinical study prior to 
enrolling a participant. Initial IRB (or IEC) approval, and all materials approved by the IRB (or 
IEC) for this study including the participant consent form and recruitment materials must be 
maintained by the investigator and made available for inspection. 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
46 
 
 
  
 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with GCP and all applicable regulatory requirements, Sage Therapeutics 
may conduct a quality assurance audit(s) at the clinical site. Please see Section 14.2 for more 
details regarding the audit process. 
The investigator must have adequate quality control practices to ensure that the study is 
performed in a manner consistent with the protocol, GCP/ICH GCP guidelines, and applicable 
regulatory requirements. The investigator is responsible for reviewing all identified protocol 
deviations. Significant protocol deviations should be reported to the IRB/IEC per the IRB/IEC’s 
written procedures. 
The investigator is responsible for supervising any individual or party to whom the investigator 
delegates study-related duties and functions conducted during the study. When the investigator 
retains the services of any individual or party to perform study-related duties and functions, the 
investigator must ensure the individual or party is qualified to perform study-related duties and 
functions and should implement procedures to ensure the integrity of the study-related duties and 
functions performed, and any data generated. 
The investigator must maintain adequate and accurate source documents and study records that 
include all pertinent observations on each of the site’s study participants. Source data must be 
attributable, legible, contemporaneous, original, accurate, and complete. Changes to source data 
should be traceable, should not obscure the original entry, and should be explained, if necessary, 
to provide clarification. 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
47 
 
 
  
 
16. 
ETHICS 
16.1. 
Ethics Review 
The final study protocol, including the final version of the Informed Consent Form, must be 
given a written and dated approval or favorable opinion by an IRB or IEC as appropriate. The 
investigator must obtain and document approval before he or she can enroll any participant into 
the study. The IRB or IEC must supply to the sponsor a list of the IRB/IEC membership and a 
statement to confirm that the IRB/IEC is organized and operates according to GCP and 
applicable laws and regulations. 
The Principal Investigator is responsible for informing the IRB or IEC of any amendment to the 
protocol in accordance with local requirements. In addition, the IRB or IEC must approve all 
advertising used to recruit participants for the study. The protocol must be re-approved by the 
IRB or IEC upon receipt of amendments and annually, as local regulations require. 
The Principal Investigator is also responsible for providing the IRB or IEC with reports of any 
reportable serious adverse drug reactions from any other study conducted with the IP. Sage 
Therapeutics will provide this information to the principal investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or IEC according to local regulations and guidelines. In addition, the Principal Investigator must 
inform the IRB/IEC and sponsor of any changes significantly affecting the conduct of the study 
and/or increasing the risk to participants (eg, violations to the protocol or urgent safety measures 
taken for participant safety). 
16.2. 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH and GCP guidelines, as well as all 
applicable regional or national regulatory requirements. 
16.3. 
Informed Consent Process 
The informed consent process for this study will be conducted by telephone/videoconference 
using electronic informed consent technology. Prior to enrolling a study participant, the 
investigator(s) will ensure that the participant is given full and adequate oral and 
written/electronic information about the nature, purpose, possible risk and benefit of the study. 
Participants must also be notified that they are free to discontinue from the study at any time. 
The participant should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
When the participant decides to participate in the study, the participant (or the participant’s 
legally authorized representative) must give informed consent by providing their handwritten 
signature executed to an electronic record. The electronic record must also capture and record the 
date that the participant (or the participant’s legally authorized representative) provides informed 
consent. If any or all of the consent process takes place remotely and is not personally witnessed 
by study personnel, the electronic system must include a method to ensure that the person 
electronically signing the informed consent is the participant who will be participating in the 
study or is the participants’ legally authorized representative. The electronic consent must be 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
48 
 
 
  
 
obtained before conducting any study procedures. The investigator must document the consent 
process in the participant’s source records. The investigator must maintain the electronic, signed 
Informed Consent Form. A copy of the electronic, signed Informed Consent Form must be given 
to the participant or to the participant’s legally authorized representative. 
Throughout the study participants should be informed of any changes made to the study and as 
new safety and or risk information becomes known. The provision of this information will be 
documented in the participant’s source records, and when applicable, an updated ICF will be 
provided. 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
49 
 
 
  
 
17. 
DATA HANDLING AND RECORDKEEPING 
17.1. 
Inspection of Records 
Sage Therapeutics or its representative(s) will be allowed to conduct site visits at the 
investigation facilities for the purpose of monitoring any aspect of the study. The investigator 
agrees to allow the monitor to inspect the facility, drug storage area, drug accountability records, 
participant charts and study source documents, and other records relative to study conduct. 
Inspection of the study by a regulatory authority may occur at any time. The investigator must 
agree to the inspection of study-related records and source documents by the regulatory authority 
representative(s). 
17.2. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for the period 
outlined in the site contract, or for a period of 2 years after the last marketing application 
approval, and until there are no pending or contemplated marketing applications in an ICH 
region or at least 2 years have elapsed since the formal discontinuation of clinical development 
of the investigational product. Sage is responsible to inform the investigator/institution as to 
when study documents no longer need to be retained. 
 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
50 
 
 
  
 
18. 
PUBLICATION POLICY 
All information concerning ZULRESSO is considered confidential and shall remain the sole 
property of Sage Therapeutics. The investigator agrees to use this information only in conducting 
the study and shall not use it for any other purposes without written approval from Sage 
Therapeutics. No publication or disclosure of study results will be permitted except as specified 
in a separate, written, agreement between Sage Therapeutics and the investigator. 


Clinical Protocol 
Sage Therapeutics, Inc. 
547-PPD-404, Version 2.0 
CONFIDENTIAL 
 
51 
 
 
  
 
19. 
LIST OF REFERENCES 
Bauman BL, Ko JY, Cox S, et al. Vital signs: Postpartum depressive symptoms and provider 
discussions about perinatal depression – United States 2018. MMWR Morb Moral Wkly Rep. 
2020;69(19):575-581. 
Bloch M, Schmidt PJ, Danaceau M, et al. Effects of gonadal steroids in women with a history of 
postpartum depression. Am J Psychiatry. 2000;157(10831472):924–930. 
CPS. Maternal depression and child development. Paediatr Child Health. 2004;9(8):575–98. 
DSM-5. Diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric 
Association. 
Kanes S, Colquhoun H, Gunduz-Bruce H, et al. Brexanolone (SAGE-547 injection) in post-
partum depression: a randomised controlled trial. Lancet. 2017 Jul 29;390(10093):480-489. 
Maguire J, Mody I. GABA(A)R plasticity during pregnancy: Relevance to postpartum 
depression. Neuron. 2008;59(2);207-13. 
Maguire J, Ferando I, Simonsen C, Mody I. Excitability changes related to GABAA receptor 
plasticity during pregnancy. J Neurosci. 2009;29(30):9592-601. 
Nappi RE, Petraglia F, Luisi S, Polatti F, Farina C, Genazzani AR. Serum allopregnanolone in 
women with postpartum “blues”. Obstet Gynecol 2001; 97: 77–80. 
Noorlander Y, Bergink V, van den Berg MP. Perceived and observed mother-child interaction at 
time of hospitalization and release in postpartum depression and psychosis. Arch Womens Ment 
Health. 2008;11(1):49–56. 
Paul SM, Purdy RH. Neuroactive steroids. FASEB J. 1992;6(6):2311-22. 
Savitz DA, Stein CR, Ye F, Kellerman L, Silverman M. The epidemiology of hospitalized 
postpartum depression in New York State, 1995-2004. Ann Epidemiol. 2011;21(6):399–406. 
Schule C, Nothdurfter C, Repprecht R. The role of allopregnanolone in depression and anxiety. 
Prog Neurobiol 2014;113:79-87. 
World Health Organization. Classification of Mental and Behavioural Disorders, 2010 (10th 
Revision). 


547-PPD-404 Summary of Changes 
Sage Therapeutics 
Version 2, Amendment 1  
 
 
1 
 
Protocol 547-PPD-404, Amendment 1 
Date of Amendment: 23 June 2021 
Assessment of Safe-Use Conditions for Administration of ZULRESSO in a Home Setting 
 
Rationale for Protocol Amendment 
The primary purpose for this protocol amendment is to address FDA comments regarding the 
recommendation to document ZULRESSO home infusion use-related issues. Associated changes 
to the amendment have been incorporated, including:  
• Addition of incidence of use-related issues related to the home administration of 
ZULRESSO as a secondary endpoint.  
• Clarification on documenting situations such as difficulties performing the tasks 
required to administer the infusion, procedural challenges, and unforeseen 
circumstances (eg, childcare issues, participant attempts to drive, etc.).  
Other changes incorporated with this amendment include the following: 
• Correction to the synopsis stating that the SAE/AESI form must be completed and 
submitted to the investigator (instead of the post infusion/loss of consciousness form) 
to align with the protocol body. 
• Clarification on the schedule of the vital signs collection (in Table 3, Schedule of 
Assessments footnotes). 
• Clarification on vital signs remote monitoring and reporting.  
• Clarification on medication error definition and reporting. 
• Clarification on documenting information regarding diagnosis, isolation, and/or 
hospitalization due to COVID-19 as part of medical history (in Table 3, Schedule of 
Assessments footnotes).  
• Clarification on the schedule of AEs and prior/concomitant medication/procedure 
collection (in Table 3, Schedule of Assessments footnotes).  
• Minor textual changes have been made throughout the protocol to increase clarity of 
the study procedures. 
• Minor corrections to typographical errors, punctuation, grammar, abbreviations, and 
formatting have been made. 
Confidential Information

SAP_001.pdf: 














D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  7  of  4 8  
 
 
 
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s, I n c.;  Pr ot o c ol  N o.:  5 4 7- P P D -4 0 4  
 
 
 
 
 
 
Q u alit y  C o ntr ol  .................................................................................................................... 3 5  
S h ell s  .................................................................................................................................. 3 6  
A p p e n di x   A .................................................................................................................................. 3 7  
A p p e n di x   B .................................................................................................................................. 4 6  
A p p e n di x   C .................................................................................................................................. 4 7  




D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  9  of  4 8  
 
 
 
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s, I n c.;  Pr ot o c ol  N o.:  5 4 7- P P D -4 0 4  
 
P ur p o s e  
 
T h e  p ur p o s e  of  t hi s st ati sti c al  a n al y si s  pl a n  ( S A P) i s t o e n s ur e  t h at t h e d at a  li sti n g s, s u m m ar y  t a bl e s a n d 
fi g ur e s  w hi c h  will  b e  pr o d u c e d,  a n d t h e  st ati sti c al  m et h o d ol o gi e s  w hi c h  will  b e  u s e d  ar e  c o m pl et e  a n d 
a p pr o pri at e t o  all o w  v ali d  c o n cl u si o n s r e g ar di n g t h e  st u d y  o bj e cti v e s.  
 
R e s p o n si biliti e s  
S y n e o s  H e alt h  will  p erf or m  t h e st ati sti c al  a n al y s e s  a n d i s  re s p o n si bl e  f or t h e pr o d u cti o n  a n d  q u alit y 
c o ntr ol  of  all t a bl e s, fi g ur e s,  a n d li sti n g s . 
 
Ti mi n g s  of  A n al y s e s  
T h e  pri m ar y  a n al y si s  i s  pl a n n e d aft er  all  s u bj e ct s  c o m pl et e  t h e fi n al st u d y  vi sit  or t er mi n at e  e arl y  fr o m t h e 
st u d y.  U nl e s s  ot h er wi s e  s p e cifi e d, t h e  a n al y si s i n cl u d e s  all  d at a  c oll e ct e d i n t h e  d at a b a s e t hr o u g h t h e 
ti m e  of t h e  d at a b a s e l o c k. 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  1 0  of  4 8  
 
 
 
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s, I n c.;  Pr ot o c ol  N o.:  5 4 7- P P D -4 0 4  
 
St u d y  O bj e cti v e s  
 
Pri m ar y  O bj e cti v e  
T h e  pri m ar y  o bj e cti v e  of  St u d y  5 4 7 -P P D -4 0 4  i s t o e v al u at e  w h et h er  t h e s af e -u s e  c o n diti o n s  f or 
a d mi ni str ati o n  of  Z U L R E S S O  c a n  b e i m pl e m e nt e d i n  a  h o m e  s etti n g.  
 
S e c o n d ar y  O bj e cti v e  
T h e  s e c o n d ar y  o bj e cti v e  of  St u d y  5 4 7 -P P D -4 0 4  i s t o i d e ntif y a n y  pr o c e s s  a n d  pr o c e d ur al  c h a n g e s  t o  b e 
i m pl e m e nt e d f or  Z U L R E S S O  a d mi ni str ati o n  at  h o m e. 
 
 
 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  1 1  of  4 8  
 
 
 
St u d y  D et ail s/ D e si g n  
 
Bri ef  D e s cri pti o n  
T hi s  i s a n  o p e n -l a b el, m ulti c e nt er  st u d y  d e si g n e d  t o a s s e s s  t h e s af e -u s e  c o n diti o n s  f or a d mi ni str ati o n  of 
Z U L R E S S O i n  a  h o m e  s etti n g t o  w o m e n  wit h  p o st p art u m  d e pr e s si o n ( P P D)  wit h t h e  o v er all  g o al t o 
i m pr o v e  p ati e nt  a c c e s s t o  Z U L R E S S O tr e at m e nt.  U p t o  5 0  p arti ci p a nt s  m a y  p arti ci p at e. 
 
T hi s  st u d y  c o n si st s  of   a s cr e e ni n g  p eri o d  of  u p  t o 2 8  d a y s  a n d   a 6 0 -h o ur  h o m e  i nf u si o n of  Z U L R E S S O 
( D a y s  1 t hr o u g h  3). 
 
T h e  s cr e e ni n g  p eri o d  b e gi n s  wit h  t h e i nf or m e d c o n s e nt  pr o c e s s,  w hi c h  m a y  b e  c o n d u ct e d  el e ctr o ni c all y. 
C o n s e nt e d  p arti ci p a nt s  will  u n d er g o r e m ot e  or i n -p er s o n  s cr e e ni n g  pr o c e d ur e s t o  d et er mi n e  eli gi bilit y.  
 
D uri n g t h e tr e at m e nt  p eri o d,  a  h o m e  h e alt h c ar e  pr o vi d er  will  arri v e  at t h e  eli gi bl e  p arti ci p a nt’ s  h o m e  o n 
D a y   1 t o i niti at e t h e 6 0 -h o ur  i ntr a v e n o u s (I V) i nf u si o n  of Z U L R E S S O.   T h e h o m e  h e alt h c ar e  pr o vi d er  m u st 
c o nfir m t h at t h e  p arti ci p a nt  c o nti n u e s t o  m e et  all t h e  eli gi bilit y  crit eri a  a n d  c o m pl et e  a n y  pr e d o s e 
a s s e s s m e nt s  pri or t o  a d mi ni st eri n g t h e i nf u si o n.  
 
T h e  o p e n -l a b el 6 0 -h o ur  i nf u si o n will  b e  a d mi ni st er e d  a s  f oll o w s: 3 0  m c g/ k g/ h o ur  ( H o ur  0 t o 4),  t h e n 
6 0  m c g/ k g/ h o ur ( H o ur  4 t o  2 4), t h e n  9 0  m c g/ k g/ h o ur ( H o ur  2 4 t o  5 2), f oll o w e d  b y  6 0  m c g/ k g/ h o ur ( H o ur 
5 2  t o 5 6),  a n d  3 0  m c g/ k g/ h o ur  ( H o ur 5 6  t o 6 0).   A pr o gr a m m a bl e  p eri st alti c  i nf u si o n p u m p  wit h  al ar m i s  t o 
b e  u s e d t o  e n s ur e  a c c ur at e  d eli v er y  of  Z U L R E S S O.  
 
S u bj e ct  S el e cti o n  
I n cl u si o n Crit eri a  
P arti ci p a nt s  m u st  m e et  all  t h e f oll o wi n g crit eri a  t o q u alif y  f or p arti ci p ati o n  i n t hi s st u d y:  
 
1.  A m b ul at or y  f e m al e ≥ 1 8  y e ar s  of  a g e.  
 
2.  P arti ci p a nt  h a s   a c urr e nt  di a g n o si s  of  P P D,  a s  c o nfir m e d  b y  t h e i n v e sti g at or. 
 
3.  P arti ci p a nt  a gr e e s  n ot  t o b e  t h e pri m ar y  c ar e gi v er  of  a n y  d e p e n d e nt s  d uri n g  t h e i nf u si o n a n d 
m u st  b e  a c c o m p a ni e d  b y  a n ot h er  a d ult ( ot h er t h a n t h e  h o m e  h e alt h c ar e  pr o vi d er)  d uri n g 
i nt er a cti o n s  wit h t h eir  c hil d(r e n). 
 
4.  P arti ci p a nt  h a s  n o  hi st or y  of  sl e e p  a p n e a  or  a n y  cli ni c all y  si g nifi c a nt  r e s pir at or y c o n diti o n s.  
 
5.  P arti ci p a nt  a gr e e s  t o r efr ai n fr o m t h e u s e  of  c e ntr al  n er v o u s  s y st e m  d e pr e s s a nt s,  s u c h  a s 
o pi oi d s,  b e n z o di a z e pi n e s,  sl e e p  ai d s  a n d fr o m  dri n ki n g  al c o h ol  d uri n g t h e i nf u si o n.  
 
6.  P arti ci p a nt  i s s uit a bl e  f or a d mi ni str ati o n  of  Z U L R E S S O  i n  a h o m e  s etti n g,  a s  p er  t h e j u d g e m e nt of 
t h e i n v e sti g at or. 
 
7.  P arti ci p a nt’ s  h o m e  i s s uit a bl e  a n d  h a s  n e c e s s ar y  pr o vi si o n s  f or a d mi ni str ati o n  of  Z U L R E S S O  a n d 
m e et s t h e f oll o wi n g  crit eri a:  
 
• 
S af e  e n vir o n m e nt  f or t h e h o m e  i nf u si o n pr o vi d er  st aff  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  1 2  of  4 8  
 
 
 
• 
A c c e s s  t o  a w or ki n g  t el e p h o n e 
 
• 
El e ctri cit y  a n d  gr o u n d e d  el e ctri c al  o utl et s  
 
• 
R u n ni n g  w at er  
 
• 
A c c e s s  t o b a c k -u p  e m er g e n c y  s er vi c e s  ( 9 1 1 s er vi c e  or  a m b ul a n c e  a v ail a bilit y)  
 
• 
S a nit ar y  e n vir o n m e nt  
 
8.  P arti ci p a nt  a gr e e s  t o st a y  at  h o m e  u ntil  t h e e n d -of -st u d y  vi sit  h a s  b e e n  c o m pl et e d,  e x c e pt  f or a 
m e di c al  e m er g e n c y.  
 
9.  P arti ci p a nt  m u st  h a v e   a n e g ati v e  pr e g n a n c y  t e st at  s cr e e ni n g  a n d  o n  D a y   1 pri or  t o t h e st art  of 
t h e  Z U L R E S S O i nf u si o n. 
 
E x cl u si o n  Crit eri a  
P arti ci p a nt s  w h o  m e et  a n y  of  t h e f oll o wi n g crit eri a  ar e  di s q u alifi e d  fr o m p arti ci p ati o n  i n t hi s st u d y:  
 
1.  P arti ci p a nt  h a s  e n d  st a g e  r e n al f ail ur e. 
 
2.  P arti ci p a nt  h a s  k n o w n  all er g y  t o pr o g e st er o n e  or  all o pr e g n a n ol o n e  or  a n y  e x ci pi e nt s  i n t h e 
br e x a n ol o n e i nj e cti o n.  
 
3.  P arti ci p a nt  i s c urr e ntl y  at  ri s k of  s ui ci d e,  a s  j u d g e d b y  t h e i n v e sti g at or, or  h a s  att e m pt e d  s ui ci d e 
a s s o ci at e d  wit h t h e  c urr e nt  e pi s o d e  of  P P D.  
 
D et er mi n ati o n   of S a m pl e  Si z e  
T h e  s a m pl e  si z e i s  b a s e d  o n  a s s u mi n g  a  7 % i n ci d e n c e r at e  of tr e at m e nt -e m er g e nt  a d v er s e  e v e nt s 
( T E A E s) l e a di n g t o i n v e sti g ati o n al pr o d u ct  (I P)  di s c o nti n u ati o n  or i nt err u pti o n,  w hi c h i s t h e r at e  o b s er v e d 
i n t h e  p o st-m ar k eti n g  s etti n g.  Wit h  5 0  p arti ci p a nt s  w h o r e c ei v e  Z U L R E S S O, t h e  pr o b a bilit y i s  0. 8 7 f or 
o b s er vi n g  at  l e a st  2 e v e nt s;  0. 6 9  f or o b s er vi n g  at  l e a st  3 e v e nt s,  a n d  0. 4 7  f or o b s er vi n g  at  l e a st  4 e v e nt s.  
 
Tr e at m e nt  A s si g n m e nt   a n d Bli n di n g  
T hi s  i s a n  o p e n -l a b el st u d y  i n w hi c h  all  p arti ci p a nt s  will  r e c ei v e Z U L R E S S O. I n  t hi s  st u d y,  p arti ci p a nt s will 
b e  a d mi ni st er e d  a  si n gl e,  c o nti n u o u s,  6 0 -h o ur, I V i nf u si o n  of  Z U L R E S S O  st arti n g  o n  D a y  1.  
 
A d mi ni str ati o n   of St u d y  M e di c ati o n  
I P will  b e  a d mi ni st er e d  a s   a si n gl e,  c o nti n u o u s,  I V i nf u si o n f or 6 0  h o ur s,  b y   a h o m e  h e alt h c ar e  pr o vi d er  i n 
t h e  p arti ci p a nt’ s  h o m e.  T h e  pr e p ar e d  a d mi xt ur e  will  b e  a d mi ni st er e d  at r o o m t e m p er at ur e. 
 
T h e  s p e cifi c  i nf u si o n d o s e  of I P  will  b e  c al c ul at e d  b a s e d  o n  w ei g ht  ( o bt ai n e d  at s cr e e ni n g  a n d  v erifi e d  o n 
D a y   1 pri or  t o t h e st art  of  t h e i nf u si o n) f or e a c h  p arti ci p a nt  a n d  will  b e  a d mi ni st er e d  a c c or di n g  t o t h e d o s e 
r e gi m e n i n  T a bl e  1. 
 
T a bl e  1.  I nf u si o n R at e  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  1 3  of  4 8  
 
 
 
Ti m e  p oi nt  
D a y  1  
0  t o  4 h o ur s  
D a y  1  
4  t o 2 4  h o ur s  
D a y  2  t o 3  
2 4  t o 5 2  h o ur s  
D a y  3  
5 2  t o 5 6  h o ur s  
D a y  3  
5 6  t o 6 0  h o ur s  
D o s e  
3 0  m c g/ k g/ h   
6 0  m c g/ k g/ h   
9 0  m c g/ k g/ h   
6 0  m c g/ k g/ h   
3 0  m c g/ k g/ h  
 
 
T h e  d o s e  r e gi m e n will  b e  pr e pr o gr a m m e d  i nt o t h e i nf u si o n p u m p  b y  t h e p h ar m a ci st  or  q u alifi e d  d e si g n e e. 
If  n e c e s s ar y, t h e  h o m e  h e alt h c ar e  pr o vi d er  m a y r e pr o gr a m t h e  p u m p i n  c o n s ult ati o n  wit h t h e  h o m e 
i nf u si o n  pr o vi d er  p h ar m a c y  st aff f or  a n y i s s u e s  u nr el at e d t o  s af et y. If t h e  p u m p  m u st  b e r e pr o gr a m m e d 
d uri n g t h e i nf u si o n  d u e t o  s af et y, t h e  h o m e  h e alt h c ar e  pr o vi d er  m u st  c o n s ult t h e i n v e sti g at or  a n d if 
n e c e s s ar y, t h e  p h ar m a ci st  or  q u alifi e d  d e si g n e e.  
 
T h e  t ar g et I V fl o w r at e f or t h e i nf u si o n p u m p  i s d eri v e d  fr o m t h e b el o w  f or m ul a. 
 
P u m p  Fl o w  R at e  ( m L/ h)  = [ W ei g ht ( k g)  x D o s e  L e v el  ( m c g/ k g/ h)] / S ol uti o n  C o n c e ntr ati o n 
( m c g/ m L) 
 
T h e  s ol uti o n  c o n c e ntr ati o n  i s e x p e ct e d  t o b e  1 0 0 0  m c g/ m L  of  s ol uti o n.  
 
D o si n g  s h o ul d  b e gi n  i n t h e m or ni n g  ( o n D a y  1)  t o all o w  f or r e c o g niti o n of  e x c e s si v e  s e d ati o n  d uri n g 
pl a n n e d  n o n -sl e e p  p eri o d s  w h e n t h e  d o s e i n cr e a s e s t o  6 0  m c g/ k g/ h o ur  a n d  s u b s e q u e ntl y t o  
9 0  m c g/ k g/ h o ur.  
 
If  e x c e s si v e  s e d ati o n  o c c ur s  at  a n y ti m e  d uri n g t h e i nf u si o n, t h e i nf u si o n  will  b e  st o p p e d  u ntil t h e 
s y m pt o m s  r e s ol v e.  T h e i nf u si o n m a y  b e  r e s u m e d at  t h e s a m e  or  l o w er d o s e  a s  cli ni c all y  a p pr o pri at e.  T h e 
i nf u si o n  will  b e i m m e di at el y  st o p p e d if  p ul s e  o xi m etr y r e v e al s  h y p o xi a.  Aft er  a n  e pi s o d e  of  h y p o xi a, t h e 
i nf u si o n  s h o ul d  n ot  b e r e s u m e d. 
 
F or  p arti ci p a nt s  w h o  d o  n ot  t ol er at e t h e 9 0  m c g/ k g/ h o ur  d o s e  f or r e a s o n s ot h er  t h a n h y p o xi a,   a r e d u cti o n 
t o  6 0  m c g/ k g/ h o ur  m a y b e  c o n si d er e d  d uri n g t h e ti m e  p eri o d t h at t h e  9 0  m c g/ k g/ h o ur i s  s c h e d ul e d t o 
o c c ur.  
 
A n y  s e d ati o n -r el at e d A E s  t h at l e a d t o d o s e  i nt err u pti o n, t er mi n ati o n, or  r e d u cti o n s h o ul d  b e  r e c or d e d a s 
A E SI s . If  ot h er i nt ol er a bl e  A E s  o c c ur, t h e i nf u si o n  will  b e  st o p p e d  u ntil t h e  s y m pt o m s r e s ol v e.  T h e 
i nf u si o n  m a y  b e r e s u m e d  at t h e  s a m e  or l o w er  d o s e  a s  cli ni c all y  a p pr o pri at e. 
 
St u d y  Pr o c e d ur e s  a n d  Fl o w c h art  
T a bl e  2.  S c h e d ul e  of  A s s e s s m e nt s  
 
 
S cr e e ni n g /  B as eli n e 
( R e m ot e  or I n- 
p ers o n)  
6 0 -H o ur  Z U L R E S S O  
H o m e  I nf usi o n 
 
P ost -I nf usi o n / E T 
St u d y  Pr o c e d ur e   
D a y  -2 8  t o D a y  - 1 
D a ys  1  t o 3  
( 0 t o 6 0  h o urs)  
D a y  3  
( > 6 0 h o urs)  
I nf or m e d C o ns e nt  
X  
 
 
I n cl usi o n/ E x cl usi o n crit eri a  
X  
X  
 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  1 4  of  4 8  
 
 
 
 
 
( c o nfir m p arti ci p a nt 
c o nti n u es t o  m e et 
eli gi bilit y  crit eri a  
pri or  t o st art of 
i nf usi o n) 
 
D e m o gr a p hi cs/ m e di c al  a n d  
s ur gi c al hist or y  
X 
 
 
B o d y  w ei g ht/ h ei g ht  1 
X 
X  ( pri or t o st art of  
i nf usi o n) 
 
Pr e g n a n c y  t est ( uri n e) 
X 
X  ( pri or t o st art of  
i nf usi o n) 
 
P arti ci p a nt  tr ai ni n g b y  h o m e  
h e alt h c ar e  pr o vi d er  
 
X  ( pri or t o st art of  
i nf usi o n) 
 
Vit al  Si g ns  2 
 
X  
 
Z U L R E S S O  i nf usi o n at  h o m e  
 
X  
 
C o nti n u o us  p uls e  o xi m etr y  
(l o c al m o nit ori n g)  3 
 
X 
 
R e m ot e  m o nit ori n g  of 
o x y g e n  s at ur ati o n a n d  h e art 
r at e  vi a  wir el ess  p uls e 
o xi m et er  
 
 
X 
 
 
M o nit ori n g  f or  e x c essi v e 
s e d ati o n 
 
X  
( e v er y  2 h o urs  d uri n g 
pl a n n e d  n o n -sl e e p 
p eri o ds)  
 
D ail y  a n d/ or  e n d -of -s hift 
c h e c klist/j o ur n al  c o m pl et e d 
b y  h o m e  h e alt h c ar e 
pr o vi d ers t o  d o c u m e nt  a n y  
us e -r el at e d iss u es 
 
 
X 
 
 
X 
P ost -i nf usi o n i nt er vi e w  of 
h o m e   h e alt h c ar e pr o vi d er(s)  
c o n d u ct e d  b y  H F  r es e ar c h ers 
 
 
 
X 
H o m e  h e alt h c ar e  pr o vi d er  t o 
c o m pl et e  a n d s u b mit 
S A E/ A E SI f or m(s), if  
a p pli c a bl e  
 
 
X 
( pri or t o l e a vi n g 
p arti ci p a nt’s  h o m e)  
A d v ers e  E v e nts  4 
X  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  1 5  of  4 8  
 
 
 
 
A b br e vi ati o n s:  B P   = bl o o d  pr e s s ur e;  E T   = e arl y  t er mi n ati o n; H F   = h u m a n  f a ct or s; H R   = h e art  r at e; R R   = 
r e s pir at or y r at e. 
 
N ot e:  U s e  of  t el e h e alt h b y  t h e i n v e sti g at or i s p er mitt e d  f or t h e s cr e e ni n g  vi sit,  i n a d diti o n  t o r e m ot e 
a s s e s s m e nt s  c o n d u ct e d  d uri n g t h e  Z U L R E S S O i nf u si o n,  a s r e q uir e d.  
1 Aft er  t h e p arti ci p a nt  pr o vi d e s  i nf or m e d c o n s e nt,   a b o d y  w ei g ht  s c al e  will  b e  d eli v er e d  t o t h e p arti ci p a nt’ s 
h o m e.  T h e  p arti ci p a nt  will  w ei g h  h er s elf  o n t h e  s c al e  a p pr o xi m at el y  7  d a y s  pri or t o  D a y  1  a n d r e p ort  h er 
b o d y  w ei g ht  t o st u d y  p er s o n n el.  B o d y  w ei g ht  at  s cr e e ni n g/ b a s eli n e  i s u s e d  t o c al c ul at e  Z U L R E S S O  d o s e 
a n d t o  b e  c o nfir m e d  b y t h e  h o m e  h e alt h c ar e  pr o vi d er  o n  D a y  1 t o  d et er mi n e  w h et h er  a n y  c h a n g e t o 
Z U L R E S S O  d o s e i s r e q uir e d.  H ei g ht  will  b e  c oll e ct e d  at  D a y  1.  
2 Vit al  si g n s i n cl u d e  B P,  R R,  H R,  a n d  o x y g e n  s at ur ati o n.  O x y g e n  s at ur ati o n,  R R,  a n d  H R  c oll e cti o n  will 
b e gi n i m m e di at el y  pri or t o t h e  st art  of t h e i nf u si o n  a n d  will  b e  m o nit or e d  c o nti n u o u sl y t hr o u g h  a  w e ar a bl e 
d e vi c e.  B P  will  b e  c oll e ct e d  pri or  t o t h e st art  of  t h e i nf u si o n, a n d  all  vit al  si g n s  will  b e  r e c or d e d i n t h e e v e nt 
of  e x c e s si v e  s e d ati o n, l o s s  of  c o n s ci o u s n e s s,  or  a n y  ot h er  a d v er s e  e v e nt  of  s p e ci al i nt er e st.  
3 O x y g e n  s at ur ati o n  will  o nl y  b e  r e c or d e d i n t h e e v e nt  of  e x c e s si v e  s e d ati o n,  l o s s of  c o n s ci o u s n e s s, 
h y p o xi a,  or  a d v er s e  e v e nt  of  s p e ci al i nt er e st ( A E SI).  
4 I nf or m ati o n r e g ar di n g di a g n o si s,  i s ol ati o n, a n d/ or  h o s pit ali z ati o n  d u e  t o C O VI D -1 9  will  b e  d o c u m e nt e d 
a s  p art  of  m e di c al  hi st or y,  A E  c oll e cti o n,  a n d  pri or/ c o n c o mit a nt  m e di c ati o n/ pr o c e d ur e  c oll e cti o n  at 
s cr e e ni n g  a n d t hr o u g h o ut t h e  st u d y.  
5 Pri or  m e di c ati o n s  will  b e  c oll e ct e d  at  s cr e e ni n g  a n d  c o n c o mit a nt  m e di c ati o n s  a n d/ or  pr o c e d ur e s  will  b e 
c oll e ct e d t h er e aft er.  
X  
Pri or/ C o n c o mit a nt 
M e di c ati o ns 
4, 5 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  1 6  of  4 8  
 
 
 
E n d p oi nt s  
 
Pri m ar y  E n d p oi nt  
•  
I n ci d e n c e of  T E A E s  l e a di n g t o d o s e  i nt err u pti o n/ di s c o nti n u ati o n. 
 
S e c o n d ar y  E n d p oi nt s  
•  
I n ci d e n c e of  n o n a d h er e n c e  wit h  t h e s af e -u s e  c o n diti o n s  f or a d mi ni str ati o n  of  Z U L R E S S O  
 
•  
I n ci d e n c e of  u s e -r el at e d i s s u e s r el at e d t o t h e h o m e  a d mi ni str ati o n  of  Z U L R E S S O  
 
•  
I n ci d e n c e of  all  T E A E s  
 
•  
I n ci d e n c e of  m e di c ati o n  err or  
 
It i s  n ot e d t h at t h e  e n d p oi nt s “I n ci d e n c e  of  n o n a d h er e n c e  wit h t h e  s af e-u s e  c o n diti o n s f or 
a d mi ni str ati o n  of  Z U L R E S S O”  a n d “I n ci d e n c e  of  u s e -r el at e d i s s u e s r el at e d t o t h e  h o m e 
a d mi ni str ati o n  of  Z U L R E S S O”  will  n ot  b e  a n al y z e d  b y  S y n e o s  H e alt h  a n d  ar e  s ol el y  li st e d f or 
c o m pl et e n e s s.   C o m pli a n c e  t o s af e -u s e  c o n diti o n s,  pr o c e s s e s,  a n d  pr o c e d ur e s  will  b e  a s s e s s e d 
s e p ar at el y  b y  h u m a n f a ct or s ( H F) r e s e ar c h er s.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  1 7  of  4 8  
 
 
 
A n al y si s  S et s  
 
E nr oll e d  S et  
T h e  E nr oll e d  S et  will  i n cl u d e all  s u bj e ct s  w h o  pr o vi d e d  writt e n  i nf or m e d c o n s e nt  t o t h e st u d y . S cr e e n 
f ail ur e s  will  n ot  b e i n cl u d e d i n t hi s  s et. 
 
S af et y  S et  
T h e  S af et y  S et  will  i n cl u d e  all  p arti ci p a nt s a d mi ni st er e d  Z U L R E S S O.   T h e S af et y  S et  will  b e  u s e d  f or all 
a n al y s e s  of  s af et y  e n d p oi nt s . 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  1 8  of  4 8  
 
 
 
G e n er al  A s p e ct s  f or St ati sti c al  A n al y si s  
 
G e n er al  M et h o d s  
•  
S u m m ari e s  will  b e  pr e s e nt e d  f or t h e S af et y  S et  u nl e s s  ot h er wi s e  s p e cifi e d..  
 
•  
C o nti n u o u s  e n d p oi nt s  will  b e  s u m m ari z e d  wit h  n u m b er ( n),  m e a n,  st a n d ar d  d e vi ati o n,  m e di a n, 
mi ni m u m,  a n d  m a xi m u m.  I n a d diti o n,  c h a n g e  fr o m  b a s eli n e v al u e s  will  b e  c al c ul at e d  at  e a c h  ti m e 
p oi nt  a n d  s u m m ari z e d  d e s cri pti v el y.  T h e  s a m e  n u m b er  of  d e ci m al  pl a c e s  a s t h e r a w  d at a  will  b e 
pr e s e nt e d  w h e n r e p orti n g  mi n  a n d  m a x,  1  m or e  d e ci m al  pl a c e t h a n i n t h e r a w  d at a  will  b e 
pr e s e nt e d  w h e n  r e p orti n g m e a n  a n d  m e di a n,  a n d   2 m or e  d e ci m al  pl a c e s  t h a n i n t h e r a w d at a  will 
b e  pr e s e nt e d  w h e n r e p orti n g  st a n d ar d  d e vi ati o n ( S D).  
 
•  
F or  c at e g ori c al  e n d p oi nt s,  d e s cri pti v e  s u m m ari e s  will i n cl u d e  c o u nt s  a n d  p er c e nt a g e s. 
P er c e nt a g e s  will  b e  pr e s e nt e d  t o  1 d e ci m al  pl a c e  u nl e s s  ot h er wi s e  s p e cifi e d;  t h e d e n o mi n at or  of 
p er c e nt a g e s  will  b e t h e  n u m b er  of  p arti ci p a nt s i n t h e  a n al y si s  s et  u s e d  u nl e s s  s p e cifi e d 
ot h er wi s e.  
 
•  
N o  f or m al si g nifi c a n c e  t e sti n g will  b e  p erf or m e d.  
 
•  
All  r el e v a nt p arti ci p a nt s  d at a  will  b e  i n cl u d e d i n li sti n g s. All  s u bj e ct s  e nt er e d  t h e d at a b a s e  will  b e 
i n cl u d e d i n  s u bj e ct  d at a li sti n g s. 
 
K e y  D efi niti o n s  
B a s eli n e  
B a s eli n e  will  b e  d efi n e d  a s  t h e l a st m e a s ur e m e nt  pri or  t o i niti ati o n of  t h e Z U L R E S S O  i nf u si o n. C h a n g e 
fr o m  B a s eli n e  will  b e  d efi n e d  a s t h e  m e a s ur e m e nt  at  e a c h ti m e  p oi nt  mi n u s t h e  B a s eli n e  val u e.  
 
St u d y  D a y  
St u d y  D a y  i s c al c ul at e d  r el ati v e t o t h e st art  d at e  of  st u d y  tr e at m e nt a n d  d efi n e d  a s  f oll o w s: 
 
•  
T h e  d a y  of  p arti ci p a nt  r e c ei vi n g t h e fir st d o s e  of  i n v e sti g ati o n al pr o d u ct  i s d e si g n at e d  a s  D a y  1.  
 
•  
F or  vi sit  d a y s  aft er  D a y  1,  st u d y  d a y   = vi sit  d at e  –  D a y   1 d at e   + 1.  
 
•  
F or  vi sit  d a y s  pri or  t o  D a y 1,  st u d y  d a y   = vi sit  d at e  –  D a y   1 d at e.   T h u s,  st u d y  d a y s  f or s cr e e ni n g 
vi sit  ar e  n e g ati v e  n u m b er s.   T h er e i s  n o “ D a y  0”.  
 
T h e  st u d y  d a y  will  b e  di s pl a y e d  i n all  r el e v a nt d at a  li sti n g s. 
 
Mi s si n g  D at a  
All  p arti ci p a nt s  will  b e  u s e d  i n t h e a n al y s e s  u si n g  all  n o n -mi s si n g  d at a  a v ail a bl e.  N o  i m p ut ati o n pr o c e s s 
will  b e  u s e d t o  e sti m at e  mi s si n g  d at a.  
 
D at e s  mi s si n g  t h e d a y,  or  b ot h  t h e d a y  a n d  m o nt h  of  t h e y e ar  will  a d h er e  t o t h e f oll o wi n g c o n v e nt i o n s t o 
cl a s sif y  T E A E s  a n d t o  cl a s sif y  pri or  a n d  c o n c o mit a nt  m e di c ati o n s.  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  1 9  of  4 8  
 
 
 
I n  g e n er al, li sti n g s  will  pr e s e nt t h e  a ct u al  p arti al  or  mi s si n g  v al u e s r at h er t h a n t h e i m p ut e d  v al u e s t h at 
m a y  b e  u s e d  i n d eri v ati o n.  I n i n st a n c e s w h er e  i m p ut e d  v al u e s will  b e  pr e s e nt e d,  i m p ut e d v al u e s  will  b e 
fl a g g e d. 
 
A d v er s e  E v e nt s  
If a n  a d v er s e  e v e nt  ( A E) st art  d at e  i s c o m pl et el y  mi s si n g,  d o  n ot  i m p ut e t h e d at e  b ut  c o n si d er it  a s  T E A E, 
u nl e s s  t h e A E  e n d  d at e  i s b ef or e  t h e i niti ati o n of  tr e at m e nt, i n w hi c h  c a s e  t h e A E  will  b e  c o n si d er e d  pri or.  
 
F or  p arti al  A E  st art  d at e s:  
 
•  
W h e n  t h e y e ar  i s k n o w n,  b ut  t h e m o nt h  a n d  d a y  i s u n k n o w n,  t h e n: 
 
o  
If t h e  y e ar  m at c h e s t h e  y e ar  of fir st  d o s e  d at e  a n d t h e  e n d  d at e (if  pr e s e nt) i s  aft er fir st 
d o s e  d at e,  or  A E  i s  o n g oi n g, t h e n i m p ut e a s  t h e m o nt h  a n d  d a y  of  e arli er  d at e  of (t h e  fir st 
d o s e  d at e  +  1  d a y, l a st  d o s e  d at e).  
 
o  
If t h e y e ar  of  A E  o n s et   < y e ar  of  i niti ati o n of  t h e tr e at m e nt, t h e n t h e m o nt h  a n d  d a y  will  b e 
s et t o  D e c e m b er  3 1 st.  
 
o  
If t h e y e ar  of  A E  o n s et   > t h e y e ar  of  i niti ati o n of  tr e at m e nt, t h e n t h e m o nt h  a n d  d a y  will  b e 
s et t o  J a n u ar y  1 st.  
 
•  
If t h e y e ar  a n d  m o nt h  ar e  k n o w n,  b ut  t h e d a y  i s u n k n o w n,  t h e n: 
 
o  
If t h e y e ar  of  A E  o n s et   = t h e y e ar  of  i niti ati o n of  t h e tr e at m e nt a n d:  
 
 
t h e m o nt h  of  A E  o n s et   = t h e m o nt h  of  i niti ati o n of  t h e tr e at m e nt, t h e n t h e d a y  will 
b e  s et t o t h e  d a y  of i niti ati o n  of t h e tr e at m e nt.  
 
 
t h e m o nt h  of  A E  o n s et   < t h e m o nt h  of  i niti ati o n of  t h e tr e at m e nt, t h e n t h e d a y  will 
b e  s et t o t h e l a st  d a y  of  m o nt h  of t h e  p arti c ul ar  y e ar.  
 
 
if t h e m o nt h  of  A E  o n s et   > t h e m o nt h  of  i niti ati o n of  t h e tr e at m e nt, t h e n t h e d a y 
will  b e  s et t o t h e  1 st  d a y  of  m o nt h.  
 
o  
If t h e y e ar  of  A E  o n s et   < t h e y e ar  of  i niti ati o n of  t h e tr e at m e nt, t h e n t h e d a y  will  b e  s et  t o 
t h e l a st  d a y  of  m o nt h  of t h e  p arti c ul ar  y e ar. 
 
o  
If t h e y e ar  of  A E  o n s et   > t h e y e ar  of  i niti ati o n of  t h e tr e at m e nt, t h e n t h e d a y  will  b e  s et  t o 
t h e  1 st  d a y  of  m o nt h. 
 
•  
If t h e i m p ut e d A E  o n s et  d at e  i s aft er  t h e A E  st o p  d at e,  t h e n t h e o n s et  d at e  will  b e  s et  t o t h e st o p 
d at e.  
 
o  
W h e n t h e  y e ar  a n d  d a y  ar e  pr e s e nt  a n d t h e  m o nt h i s  mi s si n g, tr e at it  a s if t h e  d a y i s 
mi s si n g,  a n d  o nl y  y e ar  i s pr e s e nt.   F oll o w  t h e i m p ut ati o n r ul e s f or “ y e ar i s k n o w n,  b ut  t h e 
m o nt h  a n d  d a y i s  u n k n o w n”.  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  2 0  of  4 8  
 
 
 
o  
W h e n  t h e  y e ar i s mi s si n g,  b ut  t h e m o nt h  a n d/ or  d a y  i s  k n o w n, tr e at t hi s d at e  a s  mi s si n g; 
d o  n ot i m p ut e.  
 
D at e s  i n Di s e a s e  Hi st or y  ( D at e s of  di a g n o si s,  c urr e nt  e pi s o d e,  fir st e pi s o d e)  
•  
If t h e y e ar  i s pr e s e nt  a n d  t h e m o nt h  a n d  d a y  ar e  mi s si n g,  t h e n t h e m o nt h  a n d  d a y  will  b e  s et  t o 
J a n u ar y  1.  
 
•  
If t h e y e ar  a n d  d a y  ar e  pr e s e nt  a n d  t h e m o nt h  i s mi s si n g,  t h e n t h e m o nt h  will  b e  s et  t o J a n u ar y.  
 
•  
If t h e y e ar  a n d  m o nt h  ar e  pr e s e nt  a n d  t h e d a y  i s mi s si n g,  t h e n t h e d a y  will  b e  s et  t o t h e 1 st  d a y  of 
m o nt h  
 
Pri or  a n d  C o n c o mit a nt  M e di c ati o n s 
F or t h e  p arti al  st art  d at e  of  m e di c ati o n:  
•  
If t h e y e ar  i s pr e s e nt  a n d  t h e m o nt h  a n d  d a y  ar e  mi s si n g,  t h e n t h e m o nt h  a n d  d a y  will  b e  s et  t o 
J a n u ar y  1.  
 
•  
If t h e y e ar  a n d  d a y  ar e  pr e s e nt  a n d  t h e m o nt h  i s mi s si n g,  t h e n t h e m o nt h  will  b e  s et  t o J a n u ar y.  
 
•  
If t h e y e ar  a n d  m o nt h  ar e  pr e s e nt  a n d  t h e d a y  i s mi s si n g,  t h e n t h e d a y  will  b e  s et  t o t h e 1 st  d a y  of 
m o nt h.  
 
•  
If t h e i m p ut e d st art  d at e  of  m e di c ati o n  i s aft er  t h e e n d  d at e  (i m p ut e d d at e  if a p pli c a bl e)  of 
m e di c ati o n, t h e n t h e  st art  d at e  will  b e  s et t o t h e  e n d  d at e  of  m e di c ati o n.  
 
F or  t h e p arti al  e n d  d at e  of  m e di c ati o n:  
 
•  
If t h e y e ar  i s pr e s e nt  a n d  t h e m o nt h  a n d  d a y  ar e  mi s si n g,  t h e n t h e m o nt h  a n d  d a y  will  b e  s et  t o 
eit h er  D e c e m b er  3 1  or  d at e  of  d e at h  w hi c h e v er i s  e arli er.  
 
•  
If t h e y e ar  a n d  m o nt h  ar e  pr e s e nt  a n d  t h e d a y  i s mi s si n g,  t h e n t h e d a y  will  b e  s et  t o t h e l a st d a y 
of t h e  m o nt h  or  m o nt h  of  d e at h.  
 
•  
If t h e  y e ar  a n d  d a y  ar e  pr e s e nt  a n d t h e  m o nt h i s  mi s si n g, t h e n tr e at it  a s if t h e  d a y i s  al s o 
mi s si n g.   S et  t h e m o nt h  a n d  d a y  t o b e  eit h er  D e c e m b er  3 1  or  d at e  of  d e at h  w hi c h e v er  i s e arli er.  
 
Vi sit  Wi n d o w s  
T h er e  will  b e  n o  wi n d o wi n g  f or vi sit s.  
 
P o oli n g   of C e nt er s  
N ot  a p pli c a bl e.  
 
S u b gr o u p s  
N o  s u b gr o u p  a n al y si s  i s pl a n n e d  f or t hi s st u d y.  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  2 1  of  4 8  
 
 
 
D e m o gr a p hi c,  Ot h er  B a s eli n e  C h ar a ct eri sti c s  a n d  M e di c ati o n  
 
S u bj e ct  Di s p o siti o n   a n d Wit h dr a w al s  
T h e  s u m m ari e s  of  p arti ci p a nt  di s p o siti o n  will i n cl u d e t h e  n u m b er  a n d  p er c e nt a g e s  of  p arti ci p a nt s  w h o 
w er e  s cr e e n e d,  s cr e e n f ail e d, tr e at e d,  c o m pl et e d tr e at m e nt,  di s c o nti n u e d I P  pr e m at ur el y  wit h  pri m ar y 
r e a s o n s f or di s c o nti n ui n g  I P, c o m pl et e d t h e  st u d y,  a n d  pr e m at ur el y  wit h dr e w  fr o m t h e st u d y  wit h  pri m ar y 
r e a s o n s f or  n ot  c o m pl eti n g t h e  st u d y.  All  p er c e nt a g e s  will  b e  c al c ul at e d  b a s e d  o n t h e  p arti ci p a nt s  w h o 
r e c ei v e d I P. If  a p arti ci p a nt  i s r e s cr e e n e d b e c a u s e  t h e p arti ci p a nt  h a s  b e e n   a s cr e e n  f ail ur e t h e fir st ti m e, 
t h e  st at u s  of t h e  p arti ci p a nt  will  b e  d et er mi n e d fr o m t h e  s e c o n d  s cr e e ni n g. I n t h e  c o u nt  of  s cr e e n e d 
p arti ci p a nt s,  s u c h  a  p arti ci p a nt  will  b e  c o u nt e d  o nl y  o n c e.  
 
A li sti n g  will  b e  pr o vi d e d f or  p arti ci p a nt s  s cr e e n f ail e d  wit h  pri m ar y  r e a s o n.  A  s e p ar at e li sti n g  will  b e 
pr o vi d e d  f or t h e S af et y  S et  a n d  r e p ort e d f or p arti ci p a nt s  w h o  pr e m at ur el y  di s c o nti n u e d  I P, pr e m at ur el y 
wit h dr e w fr o m t h e  st u d y  wit h r e a s o n s,  a n d  d at e  of  wit h dr a w al fr o m t h e  st u d y.  
 
Pr ot o c ol  D e vi ati o n s  
All  m aj or  pr ot o c ol  d e vi ati o n s  will  b e  s u m m ari z e d  u si n g  t h e S af et y  S et.  All  pr ot o c ol  d e vi ati o n s  ( m aj or a n d 
mi n or)  will  b e i n cl u d e d i n  a  d at a li sti n g f or t h e  E nr oll e d  S et.  
 
A n y  vi ol ati o n  of  i n cl u si o n/ e x cl u si o n crit eri a  will  al s o  b e  pr e s e nt e d  i n  a s e p ar at e  d at a  li sti n g u si n g  t h e 
E nr oll e d  S et.  
 
D e m o gr a p hi c  a n d  B a s eli n e  C h ar a ct eri sti c s  
D e m o gr a p hi c  d at a,  s u c h  a s  a g e,  r a c e, a n d  et h ni cit y,  a n d  b a s eli n e  c h ar a ct eri sti c s  ( e. g., w ei g ht,  h ei g ht), 
will  b e  s u m m ari z e d  a n d li st e d  u si n g t h e  S af et y  S et.  T h e  b el o w  c o n v er si o n s  will  b e  u s e d if  n e e d e d.  
 
H ei g ht  (i n c m)   = h ei g ht  (i n i n c h e s) * 2. 5 4 
W ei g ht (i n  k g)  =  w ei g ht (i n l b s) *  0. 4 5 3 6  
B o d y  M a s s  I n d e x ( k g/ m2 )  = W ei g ht( k g)/[ H ei g ht( m)
2 ] 
 
M e di c al/ S ur gi c al  Hi st or y  
M e di c al  a n d  s ur gi c al  hi st or y  c oll e ct e d  at  s cr e e ni n g  will  b e  c o d e d  u si n g t h e  M e di c al  Di cti o n ar y f or 
R e g ul at or y  A cti viti e s  ( M e d D R A) t er mi n ol o g y. T h e  s u m m ar y  will  b e  pr e s e nt e d  b y  pri m ar y  s y st e m  or g a n 
cl a s s ( S O C)  a n d  pr ef err e d t er m ( P T).  A  P arti ci p a nt  will  b e  c o u nt e d  o n c e  wit hi n  e a c h l e v el  of 
s u m m ari z ati o n.  M e di c al  a n d  s ur gi c al  hi st or y  will  b e li st e d.  A  s e p ar at e li sti n g  will  b e  pr o vi d e d f or 
i nf or m ati o n r e g ar di n g  di a g n o si s, i s ol ati o n,  a n d/ or  h o s pit ali z ati o n  d u e t o  C O VI D-1 9. T h e  M e d D R A 
pr ef err e d t er m s  u s e d t o  c o d e  a n d i d e ntif y  C O VI D -1 9  ar e li st e d i n  A p p e n di x  C.  
 
Di s e a s e   Hi st or y  a n d P s y c hi atri c  Hi st or y  
T h e  f oll o wi n g a n al y s e s  will  u s e  t h e S af et y  S et.  
 
Di s e a s e  hi st or y  s u c h  a s  t h e di a g n o si s  of  P P D,  c urr e nt  or  p a st  e pi s o d e,  d at e  of  d eli v er y,  o n s et  d at e  of 
P P D  a n d  h o s pit ali z ati o n  will  b e li st e d.  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  2 2  of  4 8  
 
 
 
P arti ci p a nt  hi st or y  of  p s y c hi atri c  di s or d er s  will  b e  t a b ul at e d f or e a c h  pr e -d efi n e d  p s y c hi atri c  c o n diti o n  a n d 
if  e xi st e d  wit hi n t h e  p a st  1 2  m o nt h s.  A  c orr e s p o n di n g li sti n g  will  b e  pr o vi d e d. 
 
Pri or   a n d C o n c o mit a nt  M e di c ati o n s  
M e di c ati o n s  will  b e  r e c or d e d t hr o u g h o ut t h e d ur ati o n  of  t h e st u d y  a n d  m a y  b e  c o d e d  u si n g  W orl d  H e alt h 
Or g a ni z ati o n ( W H O)  Dr u g  di cti o n ar y  Gl o b al  B 3  M ar c h  2 0 2 0,  or l at er.  
 
M e di c ati o n s  t a k e n pri or  t o t h e i niti ati o n of  t h e st art  of  I P will  b e  d e n ot e d  “ Pri or”. T h o s e  m e di c ati o n s  t a k e n 
pri or t o t h e i niti ati o n  of t h e  I P a n d  c o nti n ui n g  b e y o n d t h e  i niti ati o n  of t h e I P, or t h o s e  m e di c ati o n s  st art e d 
at t h e  s a m e ti m e  or  aft er t h e i niti ati o n  of t h e I P  will  b e  d e n ot e d “ C o n c o mit a nt”.  
 
B ot h  pri or  a n d  c o n c o mit a nt  m e di c ati o n s  will  b e  s e p ar at el y  s u m m ari z e d  b y  a n at o mi c al t h er a p e uti c 
c h e mi c al ( A T C  L e v el  3)  cl a s s  a n d  pr ef err e d  n a m e.  All  pri or  a n d  c o n c o mit a nt  m e di c ati o n s  will  b e li st e d. 
M e di c ati o n s  will  b e  pr e s e nt e d  a c c or di n g  t o w h et h er  t h e y ar e  “ Pri or” or  “ C o n c o mit a nt”, a s  d efi n e d  a b o v e.  If 
m e di c ati o n  d at e s  ar e i n c o m pl et e  a n d it i s  n ot  cl e ar  w h et h er t h e  m e di c ati o n  w a s  c o n c o mit a nt, it  will  b e 
a s s u m e d t o  b e  c o n c o mit a nt.  Mi s si n g  d at e i m p ut ati o n r ul e s  ar e  pr o vi d e d i n  S e cti o n  7. 3. 3.  
 
C o n c o mit a nt  pr o c e d ur e s  ar e  r e c or d e d o n   a s e p ar at e  el e ctr o ni c  c a s e  r e p ort f or m ( e C R F) p a g e;  t hi s will  b e 
pr e s e nt e d i n  a li sti n g  b y  p arti ci p a nt.  
 
T h e  S af et y  s et  will  b e  u s e d  f or all  t a bl e s a n d  li sti n g s. 
 
E xt e nt   of E x p o s ur e  
 
T h e  n u m b er  a n d  p er c e nt a g e  of  tr e at e d s u bj e ct s  r e c ei vi n g 6 0  h o ur s  of  i nf u si o n will  b e  t a b ul at e d.  D et ail e d 
i nf or m ati o n r e g ar di n g t h e i nf u si o n ti m e p oi nt s, pl a n n e d  d o s e s,  a ct u al  i nf u si o n r at e s, i nf u si o n int err u pti o n s, 
i nf u si o n  di s c o nti n u ati o n s,  a n d  d o s e  c h a n g e s  will  b e li st e d f or  e a c h  p arti ci p a nt. 
Tr e at m e nt  C o m pli a n c e  
N ot  a p pli c a bl e.  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  2 3  of  4 8  
 
 
 
S af et y  
 
S af et y  d at a  will  b e  li st e d b y  p arti ci p a nt  a n d  s u m m ari z e d.  All  s af et y  s u m m ari e s  will  b e  p erf or m e d  o n  t h e 
S af et y  S et.  
 
A d v er s e  E v e nt s  
A d v er s e  e v e nt s  will  b e  c o d e d  u si n g  M e d D R A  V er si o n  2 4. 0  or  hi g h er.  A  T E A E i s  d efi n e d  a s  a n  A E  wit h 
o n s et  o n  or  aft er t h e  st art  of I P. If t h e  d at e  of  a n  a d v er s e  e v e nt i s i n c o m pl et e  a n d  a n  u n a m bi g u o u s 
d et er mi n ati o n  c o ul d  n ot  b e  m a d e  wit h  r e s p e ct t o it s o n s et  ti m e v er s u s  t h e fir st d o s e  of I P  a n d/ or  l a st d o s e 
of  I P, t h e a d v er s e  e v e nt  will  b e  a s s u m e d  t o b e   a T E A E.    F or i m p ut ati o n of  mi s si n g  A E  d at e s,  pl e a s e  r ef er 
t o  S e cti o n  7. 3. 1. 
 
If  a m e di c ati o n  err or  r e s ult s i n a n  A E,  t h e r e s ulti n g A E  will  b e  r e c or d e d a n d  r e p ort e d.   T h e m e di c ati o n 
err or it s elf  will  al s o  b e  c o d e d  u si n g t h e  a p pr o pri at e  M e d D R A  V er si o n  2 4. 0  or  hi g h er.  
 
A n  o v er vi e w  s u m m ar y  t a bl e of  T E A E s  will  pr e s e nt  t h e n u m b er  a n d  p er c e nt a g e  of  p arti ci p a nt s  a s  w ell  a s 
t h e  n u m b er  of  e v e nt s f or t h e f oll o wi n g: 
 
•  
T E A E s  
 
•  
T E A E s  b y  m a xi m u m  s e v erit y  ( s e v er e > m o d er at e > mil d) 
 
•  
St u d y  dr u g  r el at e d T E A E s  
 
•  
Tr e at m e nt -e m er g e nt  S eri o u s  A d v er s e  E v e nt  ( S A E) 
 
•  
T E A E s  l e a di n g t o i nt err u pti o n/ di s c o nti n u ati o n of  I P 
 
•  
T E A E s  l e a di n g t o wit h dr a w al  fr o m t h e st u d y  
 
•  
T E A E s  l e a di n g t o d o s e  r e d u cti o n 
 
•  
T E A E s  l e a di n g t o d e at h  
 
I n ci d e n c e of  T E A E s  i n f oll o wi n g c at e g ori e s  will  b e  pr o vi d e d  b y  S O C  a n d  P T.   A p arti ci p a nt  i s c o u nt e d  o nl y 
o n c e  u n d er  e a c h  S O C  a n d  P T i n  c a s e  of  m ulti pl e  o c c urr e n c e s  of t h e  s a m e  A E.  T h e s e t a bl e s  will  b e 
s ort e d  b y  o v er all  d e s c e n di n g  fr e q u e n c y of  S O C  a n d  t h e n, wit hi n   a S O C,  b y  o v er all  d e s c e n di n g  fr e q u e n c y 
of  P T.  
 
•  
T E A E  
 
•  
T E A E s  b y  m a xi m u m  S e v erit y  
 
•  
T E A E s  b y  r el ati o n s hi p 
 
•  
S eri o u s  T E A E s  
 
•  
T E A E s  l e a di n g t o i nt err u pti o n/ di s c o nti n u ati o n of  I P 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  2 4  of  4 8  
 
 
 
•  
T E A E s  l e a di n g t o wit h dr a w al  fr o m t h e st u d y  
 
•  
T E A E s  l e a di n g t o d o s e  r e d u cti o n or  i nt err u pti o n 
 
F or  m a xi m u m  s e v erit y,  p arti ci p a nt s  will  b e  c o u nt e d  o nl y  o n c e  wit hi n  e a c h  S O C  a n d  P T  at  t h e  m a xi m u m 
s e v erit y  i n t h e f oll o wi n g or d er:  s e v er e >  m o d er at e >  mil d;  a n  A E  wit h  mi s si n g  s e v erit y  will  b e  o mitt e d  fr o m 
s e v erit y  pr e s e nt ati o n.  F or r el ati o n s hi p t o I P,  p arti ci p a nt  will  b e  c o u nt e d  o nl y  o n c e  wit hi n  e a c h  S O C  a n d 
P T  at  t h e str o n g e st  r el ati o n s hi p t o I P i n t h e f oll o wi n g or d er:  r el at e d  > n ot  r el at e d, a n  A E  wit h  r el ati o n s hi p 
mi s si n g i s tr e at e d  a s r el at e d.  
 
All  A E s t hr o u g h t h e  e n d  of t h e  st u d y  will  b e li st e d i n cl u di n g,  b ut  n ot li mit e d t o,  v er b ati m t er m,  P T,  S O C, 
r el ati o n s hi p t o st u d y  dr u g,  st art  a n d  e n d  d at e,  s eri o u s n e s s,  a cti o n  t a k e n, a n d  o ut c o m e.  S e p ar at e  li sti n g s 
will  b e  pr o vi d e d f or  S A E s,  A E s  a s s o ci at e d  wit h  d e at h,  A E s  a s s o ci at e d  wit h  st u d y tr e at m e nt 
di s c o nti n u ati o n,  a n d  A E s l e a di n g t o  d o s e r e d u cti o n.  T E A E s  will  b e fl a g g e d i n t h e li sti n g.  
 
A E SI s  
A n  A E SI i s  a n  A E/ S A E  of  s ci e ntifi c  a n d/ or  m e di c al  c o n c er n,  s p e cifi c t o t h e  pr o d u ct  or  pr o gr a m f or  w hi c h 
o n g oi n g  m o n it ori n g a n d  r a pi d c o m m u ni c ati o n  b y  t h e i n v e sti g at or t o t h e s p o n s or  i s r e q uir e d. T h e  f oll o wi n g 
e v e nt s  ar e  c o n si d er e d  A E SI s  a n d  c oll e ct e d  a s  a n  A E SI.  
 
•  
E x c e s si v e  s e d ati o n  
 
•  
L o s s  of  c o n s ci o u s n e s s  
 
•  
A n y  s e d ati o n -r el at e d A E  t h at l e a d s t o d o s e  r e d u cti o n, i nt err u pti o n, or  t er mi n ati o n 
 
All  A E SI s (i n cl u di n g t h o s e  wit h  o n s et  or  w or s e ni n g  b ef or e t h e  st art  of I P)  will  b e  s e p ar at el y  s u m m ari z e d 
a n d  li st e d, i n a d diti o n  t o b ei n g  i n cl u d e d i n t h e pri m ar y  T E A E  t a bl e s di s c u s s e d  a b o v e.  Al s o,
 
E x c e s si v e 
s e d ati o n  a n d  l o s s of  c o n s ci o u s n e s s  will  b e  r e p ort e d i n  a li sti n g f or t h e i nf or m ati o n i n cl u di n g t h e ti m e p oi nt, 
w h et h er t h e  p arti ci p a nt  w a s  a s s e s s e d f or  e x c e s si v e  s e d ati o n,  a n d t h e  d at e  a n d ti m e.  
 
 
 
Vit al  Si g n s   a n d O x y g e n  S at ur ati o n  
Vit al  si g n s  d at a  c oll e ct e d  b y  t h e r e m ot e m o nit ori n g  s y st e m i n cl u d e s  bl o o d  pr e s s ur e,  r e s pir at or y r at e, h e art 
r at e,  a n d  o x y g e n  s at ur ati o n.  T hi s  s y st e m  will  c a pt ur e  d at a  e v er y t w o  s e c o n d s  a n d t h e s e  d at a  will 
tr a n sf err e d t o  S a g e  T h er a p e uti c s i n  b ot h  u n a g gr e g at e d  a n d  a g gr e g at e d f or m at s.  T h e  u n a g gr e g at e d 
f or m at  will i n cl u d e  all  a v ail a bl e  m e a s ur e m e nt s  o n  all  p arti ci p a nt s r e c ei vi n g  Z U L R E S S O.  T h e  a g gr e g at e d 
f or m at  will i n cl u d e t h e  m e a n,  m e di a n,  1 0t h,  a n d  9 0t h p er c e ntil e s  c al c ul at e d  o n  1 5 -mi n ut e  bl o c k s  of ti m e 
t h at  ar e  ali g n e d  wit h t h e  0-1 5  mi n ut e,  1 5 -3 0  mi n ut e,  3 0 -4 5  mi n ut e,  a n d  4 5 -6 0  mi n ut e  q u a dr a nt s  of  a 
st a n d ar d  cl o c k f a c e.   F or  c o n v e ni e n c e, t h e s e  d at a ( b ot h  u n a g gr e g at e d  a n d  a g gr e g at e d)  m a y  b e r ef err e d 
t o  a s “ a ut o m at e d”  vit al  si g n s  d at a. 
 
Vit al  si g n s  d at a  m a y  al s o  b e  c oll e ct e d  dir e ctl y  b y t h e  h o m e  h e alt h c ar e  pr o vi d er( s)  a n d r e c or d e d i n t h e 
E D C  s y st e m,  p arti c ul arl y  if  a st u d y  p arti ci p a nt  e x p eri e n c e s  a n  A d v er s e  E v e nt  of  S p e ci al  I nt er e st ( A E SI) or 
h y p o xi a.   F or  c o n v e ni e n c e, t h e s e  d at a  m a y  b e r ef err e d t o  a s “ m a n u al”  vit al  si g n s  d at a.  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  2 5  of  4 8  
 
 
 
Vit al  si g n s  d at a  will  b e li st e d  a n d  s u m m ari z e d  o nl y f or  A E SI s  a n d/ or  h y p o xi a.   F or  c o n v e ni e n c e, t h e s e 
m a y  b e r ef err e d t o  a s “ e v e nt s  of i nt er e st”.   T h e  M e d D R A  pr ef err e d t er m s  u s e d t o  c o d e  a n d i d e ntif y 
h y p o xi a  ar e  li st e d i n A p p e n di x  B.    T h e e v e nt  of  i nt er e st ti m e fr a m e will  b e gi n  t w o ( 2) mi n ut e s  pri or  t o t h e 
e v e nt  o n s et t o t w o ( 2)  mi n ut e s  aft er t h e  e v e nt  of i nt er e st  h a s  st o p p e d.   E v e nt s  of i nt er e st  n ot  h a vi n g  a 
st o p ti m e  will  n ot  b e  c o n si d er e d f or t h e s e li sti n g s  a n d  s u m m ari e s.  
 
•  
E X A M P L E:  If  a p arti ci p a nt  e x p eri e n c e s  t h e o n s et  of  a n  e v e nt  of  i nt er e st at  8: 2 0  a m  a n d  t h e e v e nt 
of i nt er e st  st o p s  at  8: 5 9  a m, t h e  e v e nt  of i nt er e st ti m e fr a m e  b e gi n s  at  8: 1 8  a m  a n d  e xt e n d s t o 
9: 0 1  a m.  
 
T h e  fir st  1 5-mi n ut e  bl o c k  of  ti m e  u s e d f or  a g gr e g ati n g  p ur p o s e s  will b e t h e  8: 1 5  –  8: 3 0  a m  cl o c k 
di al  q u a dr a nt  a n d  t h e l a st 1 5 - mi n ut e bl o c k  of  ti m e u s e d  f or a g gr e g ati n g  p ur p o s e s  will  b e  t h e  9: 0 0 
–  9: 1 5  a m  cl o c k  di al  q u a dr a nt.  
 
T h er e  will  b e  f o ur ( 4) m e di a n  v al u e s  f or e a c h  m e a s ur e d  vit al  si g n  c orr e s p o n di n g  t o f o ur ( 4) 1 5 - 
mi n ut e  bl o c k s  of ti m e  a n d  t h e s e bl o c k s  of ti m e  will  b e l a b el e d ‘ 0 -1 5  mi n s’,  ’ 1 5-3 0  mi n s’,  ’ 3 0-4 5 
mi n s’,  a n d ’ 4 5 -6 0  mi n s’ f or t a b ul ati o n  p ur p o s e s.  
 
If t h e h o m e  h e alt h c ar e  pr o vi d er( s)  t a k e m a n u al  vit al  si g n s  m e a s ur e m e nt s  at  8: 2 5  a m  a n d  8: 4 0 
a m,  diff er e n c e s  b et w e e n t h e  a g gr e g at e d  m e di a n  v al u e s  a n d  m a n u al  m e a s ur e m e nt s  will  b e 
c al c ul at e d f or t h e ‘ 0 -1 5  mi n s’  a n d ’ 1 5 -3 0  mi n s’  bl o c k s  of ti m e.  
 
F or  e a c h  e v e nt  of  i nt er e st, t h e f oll o wi n g will  b e  d o n e:  
 
•  
U n a g gr e g at e d  a ut o m at e d  vit al  si g n s  d at a  will  b e li st e d  b y  mi n ut e f or t h e  e v e nt  of i nt er e st ti m e 
fr a m e ( d efi n e d  a b o v e)  al o n g  wit h t h e  m a n u al  vit al  si g n s  d at a.  I n t h e  u nli k el y  e v e nt t h at t h e  d at e 
a n d  ti m e of  m a n u al  vit al  si g n s  d at a  c oll e cti o n i n cl u d e s   a n o n -tri vi al m e a s ur e m e nt  of  s e c o n d s,  t h e 
ti m e  will  b e r o u n d e d t o t h e  n e ar e st  mi n ut e. 
 
•  
T h e  a g gr e g at e d  m e di a n  of  a ut o m at e d  vit al  si g n s  d at a f or  e a c h  1 5 -mi n ut e  wi n d o w  h a vi n g  a n y 
o v erl a p  wit h  a n  e v e nt  of  i nt er e st ti m e fr a m e ( d efi n e d a b o v e)  will  b e  c o m p ar e d  t o t h e m a n u al  vit al 
si g n s  d at a.   T hi s  will  b e  d o n e  b y  c al c ul ati n g t h e  diff er e n c e( s)  b et w e e n t h e  m e di a n  wit hi n  a  1 5 - 
mi n ut e  wi n d o w  a n d  w h at e v er  m a n u al  vit al  si g n s  d at a  e xi st  wit hi n t h e  s a m e  1 5 -mi n ut e  wi n d o w. 
T h e s e  diff er e n c e s  will  b e  s u m m ari z e d  b y  e v e nt  of i nt er e st,  vit al  si g n,  a n d  1 5 -mi n u t e ti m e p oi nt. 
S e e  d et ail e d  e x a m pl e  a b o v e..  
 
N o n a d h er e n c e  wit h  S af e -U s e  A d mi ni str ati o n   of Z U L R E S S O  
T h e  i n ci d e n c e of  n o n a d h er e n c e  wit h  t h e s af e -u s e  c o n diti o n s  f or a d mi ni str ati o n  of  Z U L R E S S O  will  n ot  b e 
a n al y z e d i n t hi s  S A P.   A n al y si s  of t h e s e  d at a  will  b e  p erf or m e d  b y  H u m a n  F a ct or s.  
 
U s e -r el at e d Criti c al  I s s u e s R el at e d  t o t h e H o m e  A d mi ni str ati o n   of Z U L R E S S O  
T h e  h o m e  h e alt h c ar e  pr o vi d er  will  r e p ort a n y  u s e -r el at e d i s s u e s of  Z U L R E S S O.  T hi s  will  n ot  b e  a n al y z e d 
i n t hi s  S A P. 
 
M e di c ati o n  Err or  
A  m e di c ati o n  err or i s  a n y  pr e v e nt a bl e  e v e nt t h at  m a y  c a u s e  or l e a d t o i n a p pr o pri at e  m e di c ati o n  u s e  or 
p ati e nt  h ar m  w hil e  t h e m e di c ati o n  i s i n t h e c o ntr ol  of  a n y  h e alt h c ar e  pr of e s si o n al,  p ati e nt,  or  c o n s u m er.  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  2 6  of  4 8  
 
 
 
F or  t h e p ur p o s e s  of  t hi s st u d y,   a m e di c ati o n  err or  c a n  t h er ef or e o c c ur  a n yti m e  o n  or  aft er  a  p h ar m a ci st 
pr e p ar e s t h e I V  b a g s f or  s hi p m e nt t o t h e  p arti ci p a nt’ s  h o m e.  
 
T h e  m e di c ati o n  err or  a n al y s e s  d e s cri b e d  i n t h e S A P  ar e  li mit e d t o d at a  a v ail a bl e  fr o m t h e a d v er s e  e v e nt 
f or m i n t h e  E D C  s y st e m.  A d diti o n al i nf or m ati o n  m a y  b e  a v ail a bl e fr o m  H u m a n  F a ct or s r e p ort s  a n d/ or 
s af et y  n arr ati v e s.  
 
M e di c ati o n  err or s  ar e  c a pt ur e d  o n t h e  a d v er s e  e v e nt  E D C f or m  a n d  c o d e d  u si n g t h e  s a m e  v er si o n  of 
M e d D R A  th at  a p pli e s  t o a d v er s e  e v e nt s.    T h e s p e cifi c  M e d D R A  pr ef err e d  t er m s u s e d  t o c o d e  a n d  i d e ntif y 
m e di c ati o n  err or s  ar e li st e d i n  A p p e n di x  A  a n d  m e di c ati o n  err or s  will  n ot  b e i n cl u d e d i n  T E A E t a bl e s,  b ut 
r at h er  h a n dl e d  s e p ar at el y. 
 
T h e  i n ci d e n c e of  m e di c ati o n  err or  will  b e  s u m m ari z e d  u si n g  t h e s a m e  f or m at a s  t h e T E A E  o v er vi e w 
s u m m ar y t a bl e  a n d  will  pr e s e nt t h e  o v er all  n u m b er  a n d  p er c e nt a g e  of  p arti ci p a nt s  e x p eri e n ci n g 
m e di c a ti o n  err or,  a s  w ell  a s t h e  n u m b er  a n d  p er c e nt a g e  of  p arti ci p a nt s  e x p eri e n ci n g  e a c h  s p e cifi c 
pr ef err e d t er m.   T h e  n u m b er  of  e v e nt s  will  al s o  b e i n cl u d e d.  
 
All  m e di c ati o n  err or s  m u st  b e  r e c or d e d a n d  s e nt  t o S a g e  or  d e si g n e e  wit hi n  2 4  h o ur s  of  t h e sit e  b e c o mi n g 
a w ar e  of t h e  m e di c ati o n  err or.  T h e  m e di c ati o n  err or  m u st  b e r e p ort e d t o  S a g e  or  d e si g n e e  e v e n if t h e 
m e di c ati o n  err or  d o e s  n ot r e s ult i n  a n  A E.  T h e l o w er l e v el t er m “ m e di c ati o n  err or”  s h o ul d  b e  a v oi d e d 
u nl e s s t h er e i s  n o  ot h er i nf or m ati o n r e p ort e d  a b o ut t h e  m e di c ati o n  err or.   I n st e a d,  a  m or e  s p e cifi c t er m 
s h o ul d  b e  pr o vi d e d.  
 
If  a m e di c ati o n  err or  r e s ult s i n a n  a d v er s e  e v e nt,  t h e a d v er s e  e v e nt  s h o ul d  b e  h a n dl e d  s e p ar at el y  a n d 
al s o  e nt er e d  o n t h e  E D C  a d v er s e  e v e nt f or m.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Uri n e  Pr e g n a n c y  T e st  
A  uri n e  pr e g n a n c y  t e st will  b e  c o n d u ct e d  f or all  p arti ci p a nt s  at  s cr e e ni n g  a n d  a g ai n  o n  D a y   1 pri or  t o t h e 
st art  of t h e i nf u si o n.  U n s c h e d ul e d  pr e g n a n c y t e st s  will  b e  c o n d u ct e d  a s  n e e d e d.   R e s ult s  of t h e 
pr e g n a n c y t e st  will  b e li st e d.  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  2 7  of  4 8  
 
 
 
I nt eri m A n al y s e s  
 
N ot  a p pli c a bl e.  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  2 8  of  4 8  
 
 
 
C h a n g e s  fr o m A n al y si s  Pl a n n e d  i n Pr ot o c ol  
 
N o n e.  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  2 9  of  4 8  
 
 
 
R ef er e n c e  Li st  
 
Cli ni c al  st u d y  pr ot o c ol,  v er si o n  2. 0,  A m e n d m e nt  1,  2 3  J u n e  2 0 2 1,  C o m p a n y:  S a g e  T h er a p e uti c s  I n c. 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  3 0  of  4 8  
 
 
 
Pr o gr a m mi n g  C o n si d er ati o n s  
 
All  T F L s,  a n d  st ati sti c al  a n al y s e s  will  b e  g e n er at e d  u si n g  S A S f or  Wi n d o w s,  R el e a s e  9. 4  or  hi g h er ( S A S 
I n stit ut e I n c., C ar y,  N C,  U S A).  C o m p ut er -g e n er at e d  t a bl e, fi g ur e a n d  li sti n g ( T F L) o ut p ut  will  a d h er e  t o t h e 
f oll o wi n g  s p e cifi c ati o n s. 
 
G e n er al  C o n si d er ati o n s  
•  
O n e  S A S  pr o gr a m  c a n  cr e at e  s e v er al  o ut p ut s,  or   a s e p ar at e  S A S  pr o gr a m  will  b e  cr e at e d  f or 
e a c h  o ut p ut  
 
•  
O n e  o ut p ut  fil e c a n  c o nt ai n  s e v er al  o ut p ut s,  or  e a c h  o ut p ut  will  b e  st or e d  i n  a s e p ar at e  fil e 
 
•  
O ut p ut  fil e s will  b e  d eli v er e d  i n W or d  f or m at or  p ort a bl e  d o c u m e nt  f or m at p df  
 
•  
N u m b eri n g  of   T F L s will  f oll o w I C H E 3  g ui d a n c e  
 
T a bl e,  Fi g ur e,  a n d  Li sti n g  F or m at  
G e n er al  
•  
All   T F L s will  b e  pr o d u c e d  i n l a n d s c a p e f or m at. 
 
•  
All   T F L s will  b e  pr o d u c e d  u si n g  t h e C o uri er  N e w  f o nt, si z e.  
 
•  
T h e  d at a  di s pl a y s  f or  T F L s will  h a v e   a mi ni m u m  bl a n k   1-i n c h m ar gi n  o n  all   4 si d e s.  
 
•  
H e a d er s  a n d  f o ot er s f or fi g ur e s will  b e  i n C o uri er  N e w  f o nt, si z e  8.  
 
•  
L e g e n d s  will  b e  u s e d  f or all  fi g ur e s wit h  m or e  t h a n o n e  v ari a bl e,  gr o u p,  or  it e m di s pl a y e d.  
 
•  
T F L s  will  b e  i n bl a c k  a n d  w hit e  ( n o c ol or).  
 
•  
S p e ci ali z e d t e xt  st yl e s,  s u c h  a s  b ol di n g, it ali c s,  b or d er s,  s h a di n g,  a n d  s u p er s cri pt e d  a n d 
s u b s cri pt e d  t e xt, will  n ot  b e  u s e d  i n t h e  T F L s, u nl e s s  ot h er wi s e  s p e cifi e d.  O n  s o m e  o c c a si o n s, 
s u p er s cri pt s  1,  2,  or  3  m a y  b e  u s e d.  
 
•  
O nl y  st a n d ar d  k e y b o ar d  c h ar a ct er s  will  b e  u s e d  i n t h e  T F L s. S p e ci al  c h ar a ct er s,  s u c h  a s  n o n - 
pri nt a bl e  c o ntr ol  c h ar a ct er s,  pri nt er -s p e cifi c,  or f o nt -s p e cifi c  c h ar a ct er s,  will  n ot  b e  u s e d. 
H e x a d e ci m al -d eri v e d  c h ar a ct er s  will  b e  u s e d,  w h er e  p o s si bl e, if t h e y  ar e  a p pr o pri at e t o  h el p 
di s pl a y  m at h  s y m b ol s ( e. g.,  μ).  C ert ai n  s u b s cri pt s  a n d  s u p er s cri pt s ( e. g.,  c m 2,  C m a x)  will  b e 
e m pl o y e d  o n  a  c a s e -b y -c a s e  b a si s.  
 
•  
Mi x e d  c a s e  will  b e  u s e d  f or all  titl e s, f o ot n ot e s, c o l u m n h e a d er s,  a n d  pr o gr a m m er -s u p pli e d 
f or m at s,  a s  a p pr o pri at e. 
 
H e a d er s  
•  
All  o ut p ut  will  h a v e  t h e f oll o wi n g h e a d er  at  t h e t o p l eft of  e a c h  p a g e:  
 
•  
S a g e  T h er a p e uti c s,  I n c. Pr ot o c ol  5 4 7 -P P D -4 0 4  ( S y n e o s H e alt h  st u d y  n u m b er  7 0 2 7 1 2 3)  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  3 1  of  4 8  
 
 
 
•  Dr aft/ Fi n al  R u n  
 
•  
All  o ut p ut  will  h a v e  P a g e  n  of  N  at t h e t o p  or  b ott o m ri g ht  c or n er  of  e a c h  p a g e.  T F L s  ar e i nt er n all y 
p a gi n at e d  i n r el ati o n t o t h e t ot al l e n gt h (i. e., t h e p a g e  n u m b er  will  a p p e ar  s e q u e nti all y  a s  p a g e   n of  N, 
w h er e  N i s t h e t ot al  n u m b er  of  p a g e s i n t h e t a bl e)  
 
•  
T h e  d at e  t h e o ut p ut  w a s  g e n er at e d  will  a p p e ar  al o n g  wit h  t h e pr o gr a m  n a m e  a s   a f o ot er o n  e a c h 
p a g e  
 
Di s pl a y  Titl e s  
•  E a c h   T F L will  b e  i d e ntifi e d b y  t h e d e si g n ati o n  a n d   a n u m er al.  (i. e., T a bl e  1 4. 1. 1).   A d e ci m al  s y st e m 
( x. y  a n d  x. y. z)  ar e  u s e d t o i d e ntif y  T F L s  wit h r el at e d  c o nt e nt s.  T h e titl e  will  b e  c e nt er e d.  T h e 
a n al y si s  s et  will  b e i d e ntifi e d  o n t h e li n e i m m e di at el y f oll o wi n g t h e titl e  a n d  will  b e  e n cl o s e d i n 
p ar e nt h e si s.   T h e titl e a n d  t a bl e d e si g n ati o n  will  b e  si n gl e  s p a c e d.  A  s oli d  li n e  s p a n ni n g t h e m ar gi n s 
will  s e p ar at e t h e  di s pl a y titl e s fr o m t h e  C ol u m n  h e a d er s.  T h er e  will  b e  o n e  bl a n k li n e  b et w e e n t h e 
l a st titl e  a n d t h e  s oli d li n e. 
T a bl e  x. y. z 
Fir st  Li n e  of  Titl e  
S e c o n d  Li n e  of  Titl e  if  Ne e d e d 
( S af et y  A n al y si s  S et) 
 
 
C ol u m n  H e a d er s  
•  
C ol u m n  h e a di n g s  will  b e  di s pl a y e d  i m m e di at el y b el o w  t h e s oli d  li n e d e s cri b e d  a b o v e  i n i niti al u p p er - 
c a s e  c h ar a ct er s.  
 
•  
I n t h e  c a s e  of  effi c a c y t a bl e s, t h e  v ari a bl e ( or  c h ar a ct eri sti c)  c ol u m n i s  o n t h e f ar l eft f oll o w e d  b y t h e 
tr e at m e nt gr o u p  c ol u m n s  a n d  t ot al c ol u m n  (if a p pli c a bl e).   P-v al u e s  m a y  b e  pr e s e nt e d  u n d er  t h e t ot al 
c ol u m n  or i n  s e p ar at e  p -v al u e  c ol u m n (if  a p pli c a bl e).  Wit hi n -tr e at m e nt  c o m p ari s o n s  m a y  h a v e  p- 
v al u e s  pr e s e nt e d i n  a r o w  b e n e at h t h e  s u m m ar y  st ati sti c s f or t h at tr e at m e nt  
 
•  
F or  n u m eri c  v ari a bl e s,  i n cl u d e ‘ u nit’ i n c ol u m n  or  r o w h e a di n g  w h e n  a p pr o pri at e  
 
•  
A n al y si s  s et  si z e s  will  b e  pr e s e nt e d  f or e a c h  tr e at m e nt gr o u p  i n t h e c ol u m n  h e a di n g  a s  ( N = x x) ( or i n 
t h e r o w  h e a di n g s, if  a p pli c a bl e).  T hi s i s  di sti n ct fr o m t h e ‘ n’  u s e d f or t h e  d e s cri pti v e  st ati sti c s 
r e pr e s e nti n g t h e  n u m b er  of  s u bj e ct s i n t h e  a n al y si s  s et 
 
•  
T h e  or d er  of  tr e at m e nt s i n t h e t a bl e s a n d  li sti n g s will  b e  Pl a c e b o  fir st i n t h e c a s e  of  pl a c e b o -c o ntr oll e d 
st u di e s  a n d  A cti v e  c o m p ar at or s fir st  i n t h e c a s e  of  a cti v e  c o m p ar at or tri al s,  f oll o w e d b y  a t ot al  c ol u m n 
(if  a p pli c a bl e) 
 
B o d y  of  t h e D at a  Di s pl a y  
1 3. 2. 5. 1.  
G e n er al  C o n v e nti o n s  
D at a  i n c ol u m n s  of   a t a bl e or  li sti n g ar e  f or m att e d a s  f oll o w s: 
 
•  
Al p h a n u m eri c  v al u e s  will  b e  l eft-j u stifi e d; 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  3 2  of  4 8  
 
 
 
•  
W h ol e  n u m b er s  ( e. g., c o u nt s)  will  b e  ri g ht j u stifi e d; a n d  
 
•  
N u m b er s  c o nt ai ni n g  fr a cti o n al p orti o n s  will  b e  d e ci m al  ali g n e d.  
 
1 3. 2. 5. 2.  
T a bl e  C o n v e nti o n s  
•  
U nit s  will  b e  i n cl u d e d w h er e  a v ail a bl e  
 
•  
F or  c at e g ori c al  p ar a m et er s,  all  c at e g ori e s  will  b e  pr e s e nt e d i n t h e t a bl e,  e v e n if  n = 0 f or  all 
tr e at m e nt gr o u p s  i n e a c h  c at e g or y.  F or  e x a m pl e,  t h e fr e q u e n c y di stri b uti o n  f or s y m pt o m  s e v erit y 
w o ul d  a p p e ar  a s:  
 
S e v erit y  
R ati n g  
N  
s e v er e  
0  
m o d er at e  
8  
mil d  
3  
 
 
W h er e  p er c e nt a g e s  ar e  pr e s e nt e d  i n t h e s e t a bl e s, z er o  p er c e nt a g e s  will  n ot  b e  pr e s e nt e d  a n d  s o  c o u nt s 
of  0  will  b e  pr e s e nt e d  a s  0  a n d  n ot  a s  0 ( 0 %).  
•  
A n  U n k n o w n  or  Mi s si n g  c at e g or y  will  b e  a d d e d  t o e a c h  p ar a m et er  f or w hi c h  i nf or m ati o n i s n ot 
a v ail a bl e f or  1  or  m or e  s u bj e ct s  
 
•  
U nl e s s  ot h er wi s e  s p e cifi e d,  t h e e sti m at e d  m e a n  a n d  m e di a n  f or  a s et  of  v al u e s  will  b e  pri nt e d  o ut 
t o  1 m or e  si g nifi c a nt  di git  t h a n t h e ori gi n al  v al u e s,  a n d  st a n d ar d  d e vi ati o n s  will  b e  pri nt e d  o ut  t o  2 
m or e  si g nifi c a nt  di git s t h a n t h e  ori gi n al  v al u e s.  T h e  mi ni m u m  a n d  m a xi m u m  will r e p ort t h e  s a m e 
si g nifi c a nt  di git s  a s t h e  ori gi n al  v al u e s.  F or  e x a m pl e,  s y st oli c  bl o o d  pr e s s ur e  will  b e  pr e s e nt e d  a s 
f oll o w s: 
N 
X X  
M e a n  
X X X. X  
St d  D e v  
X. X X  
M e di a n  
X X X. X  
Mi ni m u m  
X X X  
M a xi m u m  
X X X  
•  
P- v al u e  will  b e  pr e s e nt e d  t o  4 d e ci m al  pl a c e s  wit h   p-v al u e s  l e s s t h a n 0. 0 0 0 1  r e p ort e d a s 
“ < 0. 0 0 0 1”.  P-v al u e s l ar g er t h a n  0. 9 9 9 9  will  b e r e p ort e d  a s “ > 0. 9 9 9 9”.  
•  
P er c e nt a g e  v al u e s  will  b e  pri nt e d t o  o n e  d e ci m al  pl a c e, i n  p ar e nt h e s e s  wit h  n o  s p a c e s,  o n e 
s p a c e  aft er t h e  c o u nt ( e. g.,  7 ( 1 2. 8 %),  1 3 ( 5. 4 %)).  <  Pr e -d et er mi n e  h o w t o  di s pl a y  v al u e s t h at 
r o u n d d o w n  t o 0. 0.   A c o m m o n  c o n v e nti o n  i s t o di s pl a y  a s  ' < 0. 1', or  a s  a p pr o pri at e  wit h  a d diti o n al 
d e ci m al  pl a c e s. >  U nl e s s  ot h er wi s e  n ot e d, f or  all  p er c e nt a g e s, t h e  n u m b er  of  s u bj e ct s i n t h e 
a n al y si s  s et f or t h e tr e at m e nt  gr o u p  w h o  h a v e  a n  o b s er v ati o n  will  b e t h e  d e n o mi n at or. 
P er c e nt a g e s  aft er  z er o  c o u nt s  will  n ot  b e  di s pl a y e d  a n d  p er c e nt a g e s  e q u ati n g t o  1 0 0 %  will  b e 
pr e s e nt e d  a s  1 0 0 %,  wit h o ut  d e ci m al  pl a c e s  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  3 3  of  4 8  
 
 
 
•  
T a b ul ar  di s pl a y  of  d at a  f or m e di c al  hi st or y,  pri or/ c o n c o mit a nt  m e di c ati o n s,  a n d  all  t a b ul ar di s pl a y s 
of  a d v er s e  e v e nt  d at a  will  b e  pr e s e nt e d  b y t h e  b o d y  s y st e m, tr e at m e nt  cl a s s,  or  S O C  wit h t h e 
hi g h e st  o c c urr e n c e i n t h e  a cti v e tr e at m e nt  gr o u p i n  d e cr e a si n g  or d er,  a s s u mi n g  all t er m s  ar e 
c o d e d.  Wit hi n t h e  b o d y  s y st e m,  dr u g  cl a s s  a n d  S O C,  m e di c al  hi st or y ( b y  pr ef err e d t er m),  dr u g s 
( b y  A T C 1  c o d e),  a n d  a d v er s e  e v e nt s ( b y  pr ef err e d t er m)  will  b e  di s pl a y e d i n  d e cr e a si n g  or d er. If 
i n ci d e n c e f or  m or e t h a n  1 t er m i s i d e nti c al, t h e y  will t h e n  b e  s ort e d  al p h a b eti c all y.  Mi s si n g 
d e s cri pti v e  st ati sti c s  or  p -v al u e s  w hi c h  c a n n ot  b e  e sti m at e d  will  b e r e p ort e d  a s ‘ -’ 
 
•  
T h e  p er c e nt a g e  of  s u bj e ct s  will  n or m all y  b e  c al c ul at e d  a s  a  pr o p orti o n  of t h e  n u m b er  of  s u bj e ct s 
a s s e s s e d i n t h e r el e v a nt tr e at m e nt  gr o u p ( or  o v er all) f or t h e  a n al y si s  s et  pr e s e nt e d.  H o w e v er, 
c ar ef ul  c o n si d er ati o n  i s r e q uir e d i n m a n y  i n st a n c e s d u e  t o t h e c o m pli c at e d  n at ur e  of  s el e cti n g  t h e 
d e n o mi n at or,  u s u all y t h e  a p pr o pri at e  n u m b er  of  s u bj e ct s  e x p o s e d.  D et ail s  will  b e  d e s cri b e d i n 
f o ot n ot e s  or  pr o gr a m mi n g  n ot e s,  a s  n e c e s s ar y 
 
•  
F or  c at e g ori c al  s u m m ari e s  ( n u m b er a n d  p er c e nt a g e  of  s u bj e ct s)  w h er e   a s u bj e ct  c a n  b e  i n cl u d e d 
i n  m or e t h a n  o n e  c at e g or y,  a f o ot n ot e  or  pr o gr a m mi n g n ot e  will  b e  a d d e d  d e s cri bi n g  w h et h er t h e 
s u bj e ct i s i n cl u d e d i n t h e  s u m m ar y  st ati sti c s f or  all r el e v a nt  c at e g ori e s  or j u st  1  c at e g or y  a s  w ell 
a s t h e  s el e cti o n  crit eri a  
 
•  
W h er e   a c at e g or y  wit h   a s u b h e a di n g  ( s u c h a s  s y st e m  or g a n  cl a s s)  m u st  b e  s plit  o v er  m or e  t h a n 
o n e  p a g e,  o ut p ut t h e  s u b h e a di n g f oll o w e d  b y ‘( c o nt.)’  at t h e t o p  of  e a c h  s u b s e q u e nt  p a g e.  T h e 
o v er all  s u m m ar y  st ati sti c s f or t h e  s u b h e a di n g  s h o ul d  o nl y  b e  o ut p ut  o n t h e fir st r el e v a nt  p a g e  
 
1 3. 2. 5. 3.  
Li sti n g  C o n v e nti o n s  
•  
Li sti n g s  will  b e  s ort e d  f or pr e s e nt ati o n  i n or d er  of  tr e at m e nt gr o u p s  a s  a b o v e,  s u bj e ct  n u m b er, 
vi sit/ c oll e cti o n  d a y,  a n d  vi sit/ c oll e cti o n ti m e  
 
•  
Mi s si n g  d at a  will  b e  r e pr e s e nt e d o n  s u bj e ct  li sti n g s a s  eit h er   a h y p h e n  (‘-’) wit h   a c orr e s p o n di n g 
f o ot n ot e (‘- =  u n k n o w n  or  n ot  e v al u at e d’),  or  a s ‘ N/ A’,  wit h t h e f o ot n ot e ‘ N/ A  =  n ot  a p pli c a bl e’, 
w hi c h e v er i s  a p pr o pri at e  
 
•  
D at e s  will  b e  pri nt e d  i n S A S  D A T E 9.f or m at  (‘ D D _ M M M _ Y Y Y Y’: 0 1 J U L 2 0 0 0).  Mi s si n g  p orti o n s  of 
d at e s  will  b e r e pr e s e nt e d  o n  s u bj e ct li sti n g s  a s  d a s h e s ( --J U L 2 0 0 0).  D at e s t h at  ar e  mi s si n g 
b e c a u s e  t h e y ar e  n ot  a p pli c a bl e  f or t h e s u bj e ct  will  b e  o ut p ut  a s  ‘ N/ A’, u nl e s s  ot h er wi s e  s p e cifi e d  
 
•  
All  o b s er v e d  ti m e v al u e s  will  b e  pr e s e nt e d  u si n g   a 2 4 -h o ur   cl o c k  H H: M M or  H H: M M: S S  f or m at 
( e. g.,  1 1: 2 6: 4 5,  or  1 1: 2 6).  Ti m e  will  o nl y  b e r e p ort e d if it  w a s  m e a s ur e d  a s  p art  of t h e  st u d y 
 
•  
U nit s  will  b e  i n cl u d e d w h er e  a v ail a bl e  
 
1 3. 2. 5. 4.  
Fi g ur e  C o n v e nti o n s  
•  U nl e s s  ot h er wi s e  s p e cifi e d,  f or all  fi g ur e s, st u d y  vi sit s  will  b e  di s pl a y e d  o n  t h e  X-a xi s  a n d  e n d p oi nt 
( e. g., tr e at m e nt  m e a n  c h a n g e fr o m  B a s eli n e)  v al u e s  will  b e  di s pl a y e d  o n t h e  Y-a xi s  
 
F o ot n ot e s  
•  A  s oli d  li n e s p a n ni n g  t h e m ar gi n s  will  s e p ar at e  t h e b o d y  of  t h e d at a  di s pl a y  fr o m t h e f o ot n ot e s. 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  3 4  of  4 8  
 
 
 
•  All  f o ot n ot e s will  b e  l eft j u stifi e d wit h  si n gl e  li n e s p a ci n g  i m m e di at el y b el o w  t h e s oli d  li n e 
u n d er n e at h t h e  d at a  di s pl a y  
 
•  F o ot n ot e s  will  al w a y s  b e gi n  wit h ‘ N ot e:’  if a n  i nf or m ati o n al f o ot n ot e, or  1,  2,  3,  et c.  if  a r ef er e n c e 
f o ot n ot e.  E a c h n e w f o ot n ot e  will  st art  o n  a  n e w li n e,  w h er e  p o s si bl e  
 
•  S u bj e ct  s p e cifi c  f o ot n ot e s ar e  a v oi d e d,  w h er e  p o s si bl e  
 
•  F o ot n ot e s  will  b e  u s e d  s p ari n gl y  a n d  a d d  v al u e  t o t h e  T F L. If m or e  t h a n si x  li n e s of  f o ot n ot e s ar e 
pl a n n e d, t h e n  a  c o v er  p a g e i s  str o n gl y r e c o m m e n d e d t o  b e  u s e d t o  di s pl a y f o ot n ot e s,  a n d  o nl y 
t h o s e  e s s e nti al t o  c o m pr e h e n si o n  of t h e  d at a  will  b e r e p e at e d  o n  e a c h  p a g e 
•  T h e  l a st li n e of  t h e f o ot n ot e s e cti o n  will  b e   a st a n d ar d  s o ur c e  li n e t h at i n di c at e s t h e n a m e  of  t h e 
pr o gr a m  u s e d  t o pr o d u c e  t h e d at a  di s pl a y, t h e  d at e  t h e pr o gr a m  w a s  r u n, a n d  t h e li sti n g s o ur c e 
(i. e., ‘ Pr o gr a m:  m y pr o gr a m. s a s  Li sti n g  s o ur c e:  1 6. x. y. z’)  
 
•  S o ur c e s  a n d/ or  cr o s s -r ef er e n c e s i n f o ot n ot e s will  u s e  t h e k e y w or d  pr efi x  (i n si n g ul ar  f or m) f or e a c h 
r ef er e n c e  a n d  will  b e  s e p ar at e d  b y  a  c o m m a  w h e n  m ulti pl e  cr o s s-r ef er e n c e s  ar e  di s pl a y e d 
E x a m pl e  
Li sti n g  s o ur c e:  Li sti n g  1 6. 2. 4. 1. 1,  Li sti n g  1 6. 2. 4. 1. 2,  Li sti n g  1 6. 2. 4. 2. 1  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  3 5  of  4 8  
 
 
 
Q u alit y  C o ntr ol  
 
S A S  pr o gr a m s  ar e  d e v el o p e d t o  pr o d u c e  o ut p ut  s u c h  a s  a n al y si s  d at a  s et s,  s u m m ar y t a bl e s,  d at a 
li sti n g s, fi g ur e s, or  st ati sti c al  a n al y s e s.  A n  o v er vi e w  of  t h e d e v el o p m e nt  of  pr o gr a m s  i s d et ail e d  i n  S y n e o s 
H e alt h  D e v el o pi n g  St ati sti c al  Pr o gr a m s  st a n d ar d  o p er ati n g  pr o c e d ur e ( S O P) ( 3 9 0 7) .  
 
S y n e o s  H e alt h  D e v el o pi n g  St ati sti c al  Pr o gr a m s  S O P ( 3 9 0 7),  C o n d u cti n g t h e  Tr a n sf er  of  Bi o st ati sti c al 
D eli v er a bl e s  S O P ( 3 9 0 8)  a n d t h e  S A S  Pr o gr a m mi n g  a n d  V ali d ati o n  Pl a n  d e s cri b e s t h e  q u alit y  c o ntr ol 
pr o c e d ur e s t h at  ar e  p erf or m e d f or  all  S A S  pr o gr a m s  a n d  o ut p ut.  Q u alit y  c o ntr ol i s  d efi n e d  h er e  a s t h e 
o p er ati o n al  t e c h ni q u e s a n d  a cti viti e s  u n d ert a k e n  t o v erif y  t h at t h e S A S  pr o gr a m s  pr o d u c e  t h e o ut p ut  b y 
c h e c ki n g f or t h eir l o gi c,  effi ci e n c y  a n d  c o m m e nti n g  a n d  b y r e vi e w  of t h e  pr o d u c e d  o ut p ut.  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  3 6  of  4 8  
 
 
 
S h ell s  
 
T a bl e s,  li sti n g s, a n d  fi g ur e s h ell s  ar e  pr o vi d e d  i n  a s e p ar at e  fil e. 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  3 7  of  4 8  
 
 
 
A p p e n di x   A 
 
M e d D R A  v 2 4. 1  Pr ef err e d  T er m s  t o I d e ntif y M e di c ati o n  Err or s  
A c ci d e nt al  d e vi c e  i n g e sti o n 
A c ci d e nt al  d e vi c e  i n g e sti o n b y  a  c hil d  
A c ci d e nt al  e x p o s ur e  t o pr o d u ct  
A c ci d e nt al  e x p o s ur e  t o pr o d u ct  b y  c hil d  
A c ci d e nt al  e x p o s ur e  t o pr o d u ct  b y  el d erl y  p er s o n  
A c ci d e nt al  e x p o s ur e  t o pr o d u ct  p a c k a gi n g  
A c ci d e nt al  e x p o s ur e  t o pr o d u ct  p a c k a gi n g  b y  c hil d  
A c ci d e nt al  o v er d o s e  
A c ci d e nt al  p oi s o ni n g  
A c ci d e nt al  u n d er d o s e  
A c ci d e nt al  u s e  of  pl a c e b o  
B o o st er  d o s e  mi s s e d  
Cir c u m st a n c e  or  i nf or m ati o n c a p a bl e  of  l e a di n g t o d e vi c e  u s e  err or  
Cir c u m st a n c e  or  i nf or m ati o n c a p a bl e  of  l e a di n g t o m e di c ati o n  err or  
C o m pli c ati o n  of  d e vi c e  i n s erti o n 
C o m pli c ati o n  of  d e vi c e  r e m o v al 
C o m pli c ati o n  of  dr u g  d eli v er y  s y st e m  r e m o v al 
C o ntr ai n di c at e d  d e vi c e  u s e d  
C o ntr ai n di c at e d  pr o d u ct  a d mi ni st er e d  
C o ntr ai n di c at e d  pr o d u ct  pr e s cri b e d  
C o ntr ai n di c ati o n  t o m e di c al  tr e at m e nt 
C o ntr ai n di c ati o n  t o v a c ci n ati o n  
D e pr e s cri bi n g  err or  
D e vi c e  a d h e si o n  i s s u e 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  3 8  of  4 8  
 
 
 
D e vi c e  c o n n e cti o n  i s s u e 
D e vi c e  d e pl o y m e nt  i s s u e 
D e vi c e  diffi c ult  t o u s e  
D e vi c e  di s p e n si n g  err or  
D e vi c e  i nf u si o n i s s u e 
D e vi c e  m ai nt e n a n c e  i s s u e 
D e vi c e  m alf u n cti o n  
D e vi c e  m o nit ori n g  pr o c e d ur e  n ot  p erf or m e d  
D e vi c e  pl a c e m e nt  i s s u e 
D e vi c e  pr o gr a m mi n g  err or  
D e vi c e  u s e  c o nf u si o n  
D e vi c e  u s e  err or  
D e vi c e  u s e  i s s u e 
D e vi c e -d e vi c e  i n c o m p ati bilit y 
Di s c o nti n u e d  pr o d u ct  a d mi ni st er e d  
D o c u m e nt e d  h y p er s e n siti vit y  t o a d mi ni st er e d  pr o d u ct  
D o s e  c al c ul ati o n  err or  
Dr u g  a d mi ni st er e d  i n wr o n g  d e vi c e  
Dr u g  d eli v er y  s y st e m  i s s u e 
Dr u g  d eli v er y  s y st e m  m alf u n cti o n  
Dr u g  di s p e n s e d  t o wr o n g  p ati e nt  
Dr u g  d o s e  o mi s si o n  b y  d e vi c e  
Dr u g  d o s e  titr ati o n n ot  p erf or m e d  
Dr u g  eff e cti v e  f or u n a p pr o v e d  i n di c ati o n 
Dr u g  i n eff e cti v e f or u n a p pr o v e d  i n di c ati o n 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  3 9  of  4 8  
 
 
 
Dr u g  m o nit ori n g  pr o c e d ur e  i n c orr e ctl y p erf or m e d  
Dr u g  m o nit ori n g  pr o c e d ur e  n ot  p erf or m e d  
Dr u g  titr ati o n err or  
D u pli c at e  t h er a p y err or  
E x pir e d  d e vi c e  u s e d  
E x pir e d  pr o d u ct  a d mi ni st er e d  
E x p o s ur e  t o c o nt a mi n at e d  d e vi c e  
E x p o s ur e  vi a  c o nt a mi n at e d  d e vi c e  
E x p o s ur e  vi a  dir e ct  c o nt a ct  
E x p o s ur e  vi a  e y e  c o nt a ct  
E x p o s ur e  vi a  i n g e sti o n 
E x p o s ur e  vi a  i n h al ati o n 
E x p o s ur e  vi a  p art n er  
E x p o s ur e  vi a  s ki n  c o nt a ct  
E x p o s ur e  vi a  u n k n o w n  r o ut e 
E xtr a  d o s e  a d mi ni st er e d  
F ail ur e  of  c hil d  r e si st a nt pr o d u ct  cl o s ur e  
F ail ur e  t o s u s p e n d  m e di c ati o n  
I m pl a nt ati o n c o m pli c ati o n  
I n a d e q u at e a s e pti c  t e c h ni q u e i n u s e  of  pr o d u ct  
I n a p pr o pri at e s c h e d ul e  of  pr o d u ct  a d mi ni str ati o n  
I n a p pr o pri at e s c h e d ul e  of  pr o d u c e  di s c o nti n u ati o n  
I n c o m pl et e c o ur s e  of  v a c ci n ati o n  
I n c orr e ct di s p o s al  of  pr o d u ct  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  4 0  of  4 8  
 
 
 
I n c orr e ct d o s a g e  a d mi ni st er e d  
I n c orr e ct d o s e  a d mi ni st er e d  
I n c orr e ct d o s e  a d mi ni st er e d  b y  d e vi c e  
I n c orr e ct d o s e  a d mi ni st er e d  b y  pr o d u ct  
I n c orr e ct dr u g  a d mi ni str ati o n  r at e 
I n c orr e ct pr o d u ct  a d mi ni str ati o n  d ur ati o n  
I n c orr e ct pr o d u ct  d o s a g e  f or m a d mi ni st er e d  
I n c orr e ct pr o d u ct  f or m ul ati o n a d mi ni st er e d  
I n c orr e ct r o ut e of  pr o d u ct  a d mi ni str ati o n  
I nj ur y a s s o ci at e d  wit h  d e vi c e  
I nt er c e pt e d a c ci d e nt al  e x p o s ur e  t o pr o d u ct  b y  c hil d  
I nt er c e pt e d m e di c ati o n  err or  
I nt er c e pt e d pr o d u ct  a d mi ni str ati o n  err or  
I nt er c e pt e d pr o d u ct  di s p e n si n g  err or  
I nt er c e pt e d pr o d u ct  m o nit ori n g  err or  
I nt er c e pt e d pr o d u ct  pr e p ar ati o n  err or  
I nt er c e pt e d pr o d u ct  pr e s cri bi n g  err or  
I nt er c e pt e d pr o d u ct  s el e cti o n  err or  
I nt er c e pt e d pr o d u ct  st or a g e  err or  
I nt er c e pt e d wr o n g  p ati e nt  s el e ct e d  
I nt er c h a n g e of  v a c ci n e  pr o d u ct s  
L a b ell e d  dr u g -di s e a s e  i nt er a cti o n i s s u e 
L a b ell e d  dr u g -di s e a s e  i nt er a cti o n m e di c ati o n  err or  
L a b ell e d  dr u g -dr u g  i nt er a cti o n i s s u e 


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  4 1  of  4 8  
 
 
 
L a b ell e d  dr u g -dr u g  i nt er a cti o n m e di c ati o n  err or  
L a b ell e d  dr u g -f o o d i nt er a cti o n i s s u e 
L a b ell e d  dr u g -f o o d i nt er a cti o n m e di c ati o n  err or  
L a c k  of  a d mi ni str ati o n  sit e  r ot ati o n 
L a c k  of  a p pli c ati o n  sit e  r ot ati o n 
L a c k  of  i nf u si o n sit e  r ot ati o n 
L a c k  of  i nj e cti o n sit e  r ot ati o n 
L a c k  of  v a c ci n ati o n  sit e  r ot ati o n 
M e di c al  d e vi c e  m o nit ori n g  err or  
M e di c ati o n  err or  
M ulti pl e  u s e  of  si n gl e -u s e  pr o d u ct  
N e e dl e  i s s u e 
O c c u p ati o n al  e x p o s ur e  t o pr o d u ct  
O c c u p ati o n  e x p o s ur e  t o r a di ati o n 
O v er d o s e  
P ar a v e n o u s  dr u g  a d mi ni str ati o n  
P o or  q u alit y  d e vi c e  u s e d  
P o or  q u alit y  pr o d u ct  a d mi ni st er e d  
Pr e s cri b e d  o v er d o s e  
Pr e s cri b e d  u n d er d o s e  
Pr o d u ct  a d h e si o n  i s s u e 
Pr o d u ct  a d mi ni st er e d  at  i n a p pr o pri at e sit e  
Pr o d u ct  a d mi ni st er e d  b y  wr o n g  p er s o n  
Pr o d u ct  a d mi ni st er e d  t o p ati e nt  of  i n a p pr o pri at e a g e  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  4 2  of  4 8  
 
 
 
Pr o d u ct  a d mi ni str ati o n  err or  
Pr o d u ct  a d mi ni str ati o n  i nt err u pt e d 
Pr o d u ct  a p p e ar a n c e  c o nf u si o n  
Pr o d u ct  b ar c o d e  i s s u e 
Pr o d u ct  c o m mi n gli n g  
Pr o d u ct  c o m m u ni c ati o n  i s s u e 
Pr o d u ct  c o m p o u n di n g  q u alit y  i s s u e 
Pr o d u ct  c o nf u si o n  
Pr o d u ct  d eli v er y  m e c h a ni s m  i s s u e 
Pr o d u ct  d e si g n  c o nf u si o n  
Pr o d u ct  di s p e n si n g  err or  
Pr o d u ct  di s p e n si n g  i s s u e 
Pr o d u ct  d o s a g e  f or m c o nf u si o n  
Pr o d u ct  d o s a g e  f or m i s s u e 
Pr o d u ct  d o s e  o mi s si o n  i n err or  
Pr o d u ct  d o s e  o mi s si o n  i s s u e 
Pr o d u ct  e x pir ati o n  d at e  i s s u e 
Pr o d u ct  i d e ntifi c ati o n n u m b er  i s s u e 
Pr o d u ct  l a b el c o nf u si o n  
Pr o d u ct  l a b el i s s u e 
Pr o d u ct  l a b el o n  wr o n g  pr o d u ct  
Pr o d u ct  l ot n u m b er  i s s u e 
Pr o d u ct  m o nit ori n g  err or  
Pr o d u ct  n a m e  c o nf u si o n  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  4 3  of  4 8  
 
 
 
Pr o d u ct  p a c k a gi n g  c o nf u si o n  
Pr o d u ct  p a c k a gi n g  diffi c ult  t o o p e n  
Pr o d u ct  p a c k a gi n g  i s s u e 
Pr o d u ct  pr e p ar ati o n  err or  
Pr o d u ct  pr e p ar ati o n  i s s u e 
Pr o d u ct  pr e s cri bi n g  err or  
Pr o d u ct  pr e s cri bi n g  i s s u e 
Pr o d u ct  r e c o n stit uti o n q u alit y  i s s u e 
Pr o d u ct  s el e cti o n  err or  
Pr o d u ct  st or a g e  err or  
Pr o d u ct  s u b stit uti o n  err or  
Pr o d u ct  t e m p er at ur e e x c ur si o n  i s s u e 
Pr o d u ct  u s e  c o m pl ai nt  
Pr o d u ct  u s e  i n u n a p pr o v e d  i n di c ati o n 
Pr o d u ct  u s e  i n u n a p pr o v e d  t h er a p e uti c e n vir o n m e nt  
Pr o d u ct  u s e  i s s u e 
Pr o st h eti c  c ar di a c  v al v e  m alf u n cti o n  
R a di ati o n  o v er d o s e  
R a di ati o n  u n d er d o s e  
R e c all e d  pr o d u ct  a d mi ni st er e d  
Si n gl e  c o m p o n e nt  of  a  t w o-c o m p o n e nt  pr o d u ct  a d mi ni st er e d  
S yri n g e  i s s u e 
T h er a p e uti c  dr u g  m o nit ori n g  a n al y si s  i n c orr e ctl y p erf or m e d  
T h er a p e uti c  dr u g  m o nit ori n g  a n al y si s  n ot  p erf or m e d  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  4 4  of  4 8  
 
 
 
T h er a p e uti c  pr o d u ct  eff e cti v e  f or u n a p pr o v e d  i n di c ati o n 
T h er a p e uti c  pr o d u ct  i n eff e cti v e f or u n a p pr o v e d  i n di c ati o n 
Tr a n s cri pti o n  m e di c ati o n  err or  
Tr a n sf u si o n  wit h  i n c o m p ati bl e bl o o d  
Tr e at m e nt  n o n c o m pli a n c e  
U n d er d o s e  
U ni nt e nti o n al  m e di c al  d e vi c e  r e m o v al 
U ni nt e nti o n al  u s e  f or u n a p pr o v e d  i n di c ati o n 
V a c ci n ati o n  err or  
Wr o n g  d e vi c e  u s e d  
Wr o n g  d o s a g e  f or m 
Wr o n g  d o s a g e  f or m ul ati o n 
Wr o n g  d o s e  
Wr o n g  dr u g  
Wr o n g  p ati e nt  
Wr o n g  p ati e nt  r e c ei v e d pr o d u ct  
Wr o n g  pr o d u ct  a d mi ni st er e d  
Wr o n g  pr o d u ct  pr o c ur e d  
Wr o n g  pr o d u ct  st or e d  
Wr o n g  r at e 
Wr o n g  r o ut e 
Wr o n g  s c h e d ul e  
Wr o n g  str e n gt h  
Wr o n g  t e c h ni q u e i n d e vi c e  u s a g e  pr o c e s s  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  4 5  of  4 8  
 
 
 
Wr o n g  t e c h ni q u e i n pr o d u ct  u s a g e  pr o c e s s  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  4 6  of  4 8  
 
 
 
A p p e n di x   B 
 
M e d D R A  v 2 4. 1  Pr ef err e d  T er m s  t o I d e ntif y H y p o xi a  
H y p o xi a  
O x y g e n  s at ur ati o n  d e cr e a s e d  
O x y g e n  s at ur ati o n  a b n or m al  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  4 7  of  4 8  
 
 
 
A p p e n di x   C 
 
M e d D R A  v 2 4. 1  Pr ef err e d  T er m s  t o I d e ntif y C O VI D -1 9  
A nti -pl at el et  f a ct or 4  a nti b o d y  p o siti v e  
A nti vir al  pr o p h yl a xi s  
A nti vir al  tr e at m e nt 
A s y m pt o m ati c  C O VI D -1 9  
Br e a kt hr o u g h  C O VI D -1 9  
C o n g e nit al  C O VI D -1 9  
C or o n a vir u s  i nf e cti o n 
C or o n a vir u s  p n e u m o ni a  
C or o n a vir u s  t e st 
C or o n a vir u s  t e st n e g ati v e  
C or o n a vir u s  t e st p o siti v e  
C O VI D -1 9  
C O VI D -1 9  i m m u ni s ati o n 
C O VI D -1 9  p n e u m o ni a  
C O VI D -1 9  pr o p h yl a xi s  
C O VI D -1 9  s cr e e ni n g  
C O VI D -1 9  tr e at m e nt 
E x p o s ur e  t o c o m m u ni c a bl e  di s e a s e  
E x p o s ur e  t o S A R S -C o V -2  
M ulti s y st e m  i nfl a m m at or y s y n dr o m e  
M ulti s y st e m  i nfl a m m at or y s y n dr o m e  i n a d ult s  
M ulti s y st e m  i nfl a m m at or y s y n dr o m e  i n c hil dr e n  


D o c u Si g n  E n v el o p e  I D: B A B D 1 6 F B -C 8 8 9 -4 D 6 E -8 B 0 6 -4 D C 5 E 9 D 5 8 7 B 3  
St ati sti c al  A n al y si s  Pl a n  f or I nt er v e nti o n al St u di e s  
S p o n s or:  S a g e  T h er a p e uti c s,  I n c.; Pr ot o c ol  N o.:  5 4 7 -P P D -4 0 4  
T hi s  d o c u m e nt  i s c o nfi d e nti al.  
S A P  V er si o n:  1. 1,  0 9 -S e p -2 0 2 2  
C o ntr oll e d  D o c u m e nt I D:  3 9 0 3 A. 0 2 ,  Eff e cti v e  D at e  3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s:  T M F  
P a g e  4 8  of  4 8  
 
 
 
O c c u p ati o n al  e x p o s ur e  t o S A R S -C o V -2  
P n e u m o ni a  vir al  
P o st -a c ut e  C O VI D -1 9  s y n dr o m e  
S A R S -C o V -2  a nti b o d y  t e st 
S A R S -C o V -2  a nti b o d y  t e st n e g ati v e  
S A R S -C o V -2  a nti b o d y  t e st p o siti v e  
S A R S -C o V -2  c arri er  
S A R S -C o V -2  R N A  
S A R S -C o V -2  R N A  d e cr e a s e d  
S A R S -C o V -2  R N A  fl u ct u ati o n 
S A R S -C o V -2  R N A  i n cr e a s e d 
S A R S -C o V -2  R N A  u n d et e ct a bl e  
S A R S -C o V -2  s e p si s  
S A R S -C o V -2  t e st 
S A R S -C o V -2  t e st f al s e n e g ati v e  
S A R S -C o V -2  t e st f al s e p o siti v e  
S A R S -C o V -2  t e st n e g ati v e  
S A R S -C o V -2  t e st p o siti v e  
S A R S -C o V -2  vir a e mi a  
S u s p e ct e d  C O VI D -1 9  
T hr o m b o si s  wit h  t hr o m b o c yt o p e ni a s y n dr o m e  
V a c ci n e  d eri v e d  S A R S -C o V -2  i nf e cti o n 


 
 
C ertifi c at e  Of  C o m pl eti o n  
 
E n v el o p e I d:  B A B D 1 6 F B C 8 8 9 4 D 6 E 8 B 0 6 4 D C 5 E 9 D 5 8 7 B 3 
St at u s:  C o m pl et e d 
S u bj e ct:  Pl e a s e  D o c u Si g n:  S a g e  5 4 7- P P D - 4 0 4  Fi n al  S A P  v 1. 1. d o c x 
S o ur c e  E n v el o p e:  
D o c u m e nt  P a g e s:  4 8  
Si g n at ur e s:  6 
E n v el o p e  Ori gi n at or:  
C ertifi c at e  P a g e s:  6 
I niti al s:  0 
 
A ut o N a v:  E n a bl e d  
E n v el o p eI d  St a m pi n g:  E n a bl e d  
Ti m e  Z o n e: ( U T C- 0 5: 0 0)  E a st er n  Ti m e ( U S  &  C a n a d a)  
 
I P  A d dr e s s:
 
 
R e c or d  Tr a c ki n g  
 
St at u s:  Ori gi n al  
0 9- S e p- 2 0 2 2 |  1 5: 0 8  
H ol d er:   
 
 
L o c ati o n:  D o c u Si g n  
 
 
 
 
S a g e  T h er a p e uti c s -  P art  1 1 
S e c urit y  L e v el:  E m ail,  A c c o u nt  A ut h e nti c ati o n  
( R e q uir e d) 
Si g n at ur e  A d o pti o n:  Pr e- s el e ct e d  St yl e  
Si g n at ur e  I D: 
1 1 4 6 8 B F E- 8 F B A - 4 E D 3-B 4 B E -A 5 0 1 1 7 4 8 8 E 0 D  
U si n g I P  A d dr e s s: 
 
S e nt:  0 9- S e p- 2 0 2 2 |  1 5: 1 1  
Vi e w e d:  0 9- S e p- 2 0 2 2 |  1 5: 2 4 
Si g n e d:  0 9- S e p- 2 0 2 2 |  1 5: 2 5  
 
 
 
 
 
El e ctr o ni c  R e c or d  a n d  Si g n at ur e  Di s cl o s ur e:  
N ot  Off er e d  vi a  D o c u Si g n  
Wit h  Si g ni n g  A ut h e nti c ati o n  vi a   D o c u Si g n  p a s s w or d 
Wit h  Si g ni n g  R e a s o n s ( o n  e a c h t a b): 
I  a p pr o v e t hi s d o c u m e nt  
 
 
 
S e c urit y   L e v el: E m ail,   A c c o u nt  A ut h e nti c ati o n 
( R e q uir e d) 
 
 
 
 
 
 
 
 
 
El e ctr o ni c  R e c or d  a n d  Si g n at ur e  Di s cl o s ur e:  
N ot  Off er e d  vi a  D o c u Si g n  
 
 
 
Si g n at ur e  A d o pti o n:  Pr e - s el e ct e d  St yl e 
Si g n at ur e I D: 
2 A 4 D D C F 8- F A 9 0 - 4 3 8 2- A 1 5 8-0 3 D 4 0 F E 7 7 A 7 C  
U si n g I P  A d dr e s s: 
 
 
Wit h  Si g ni n g  A ut h e nti c ati o n  vi a   D o c u Si g n  p a s s w or d 
Wit h  Si g ni n g  R e a s o n s ( o n  e a c h t a b): 
I  a p pr o v e t hi s d o c u m e nt  
S e nt:  0 9- S e p- 2 0 2 2 |  1 5: 1 1  
Vi e w e d:  0 9- S e p- 2 0 2 2 |  1 6: 1 1 
Si g n e d:  0 9- S e p- 2 0 2 2 |  1 6: 1 2  
 
 
 
S a g e  T h er a p e uti c s -  P art  1 1  
S e c urit y  L e v el:  E m ail,  A c c o u nt  A ut h e nti c ati o n  
( R e q uir e d) 
Si g n at ur e  A d o pti o n:  Pr e- s el e ct e d  St yl e  
Si g n at ur e  I D: 
9 1 A D A 9 1 3- B E C 1 - 4 E 0 6-A 0 E 6 -9 B D 6 F 2 8 0 3 3 1 6  
U si n g I P  A d dr e s s: 
 
S e nt:  0 9- S e p- 2 0 2 2 |  1 5: 1 1  
Vi e w e d:  0 9- S e p- 2 0 2 2 |  1 5: 1 7 
Si g n e d:  0 9- S e p- 2 0 2 2 |  1 5: 1 8  
 
 
 
 
 
El e ctr o ni c  R e c or d  a n d  Si g n at ur e  Di s cl o s ur e:  
Wit h  Si g ni n g  A ut h e nti c ati o n  vi a   D o c u Si g n  p a s s w or d 
Wit h  Si g ni n g  R e a s o n s ( o n  e a c h t a b): 
I  a p pr o v e t hi s d o c u m e nt  
Si g n er  E v e nt s  
Si g n at ur e  
Ti m e st a m p  






 
El e ctr o ni c  R e c or d  a n d  Si g n at ur e  Di s cl o s ur e  cr e at e d  o n:  1 0- A u g- 2 0 2 0 |  1 0: 1 2 
P arti e s  a gr e e d t o: 
 
 
 
 
E L E C T R O NI C  R E C O R D  A N D  SI G N A T U R E  DI S C L O S U R E  
 
Fr o m ti m e t o ti m e,  S a g e  T h er a p e uti cs  -  P art  1 1 ( w e,  us  or  C o m p a n y)  m a y  b e r e q uir e d  b y l a w t o 
pr o vi d e t o  y o u  c ert ai n  writt e n  n oti c es  or  dis cl os ur es.  D es cri b e d  b el o w  ar e t h e t er ms  a n d 
c o n diti o ns  f or  pr o vi di n g t o  y o u s u c h  n oti c es  a n d dis cl os ur es  el e ctr o ni c all y t hr o u g h  t h e  D o c u Si g n 
s yst e m.  Pl e as e r e a d t h e i nf or m ati o n  b el o w  c ar ef ull y  a n d t h or o u g hl y,  a n d if  y o u  c a n  a c c ess t his 
i nf or m ati o n  el e ctr o ni c all y t o  y o ur s atisf a cti o n  a n d  a gr e e t o t his  El e ctr o ni c  R e c or d  a n d  Si g n at ur e 
Dis cl os ur e  ( E R S D), pl e as e   c o nfir m  y o ur  agr e e m e nt   b y s el e cti n g t h e c h e c k - b o x  n e xt t o ‘I a gr e e  t o 
us e  el e ctr o ni c r e c or ds  a n d si g n at ur es’  b ef or e  cli c ki n g ‘ C O N TI N U E’  wit hi n t h e  D o c u Si g n  
s yst e m. 
 
 
G etti n g  p a p e r  c o pi es  
 
At  a n y ti m e,  y o u  m a y r e q u est fr o m  us  a  p a p er  c o p y  of  a n y r e c or d  pr o vi d e d  or  m a d e  a v ail a bl e 
el e ctr o ni c all y t o  y o u  b y  us.  Y o u  will  h a v e t h e  a bilit y t o  d o w nl o a d  a n d  pri nt  d o c u m e nts  w e s e n d 
t o  y o u t hr o u g h t h e  D o c u Si g n s yst e m  d uri n g  a n d i m m e di at el y aft er  t h e sig ni n g  s essi o n  a n d, if  y o u 
el e ct t o  cr e at e  a  D o c u Si g n  a c c o u nt,  y o u  m a y  a c c ess t h e  d o c u m e nts f or  a li mit e d  p eri o d  of ti m e 
( us u all y  3 0  d a ys) aft er  s u c h  d o c u m e nts ar e  first s e nt t o  y o u. Aft er  s u c h ti m e, if  y o u wis h  f or  us t o 
s e n d  y o u  p a p er  c o pi es  of  a n y s u c h  d o c u m e nts fr o m  o ur  offi c e t o  y o u,  y o u  will  b e  c h ar g e d  a 
$ 0. 0 0  p er- p a g e  f e e. Y o u  m a y  r e q u est d eli v er y   of s u c h  p a p er c o pi es  fr o m  us  b y f oll o wi n g t h e 
pr o c e d ur e  d es cri b e d  b el o w.  
 
 
Wit h d r a wi n g   y o u r c o ns e nt  
 
If  y o u  d e ci d e t o r e c ei v e  n oti c es  a n d  dis cl os ur es fr o m  us  el e ctr o ni c all y,  y o u  m a y  at  a n y ti m e 
c h a n g e  y o ur  mi n d   a n d t ell  us t h at t h er e aft er  y o u w a nt  t o r e c ei v e r e q uir e d  n oti c es  a n d dis cl os ur es 
o nl y i n  p a p er f or m at.  H o w  y o u  m ust i nf or m  us  of  y o ur  d e cisi o n t o r e c ei v e f ut ur e  n oti c es  a n d 
dis cl os ur e i n  p a p er f or m at  a n d  wit h dr a w  y o ur  c o ns e nt t o r e c ei v e  n oti c es  a n d  dis cl os ur es 
el e ctr o ni c all y is  d es cri b e d  b el o w. 
 
 
C o ns e q u e n c es   of c h a n gi n g   y ou r  mi n d  
 
If  y o u  el e ct t o r e c ei v e r e q uir e d  n oti c es  a n d  dis cl os ur es  o nl y i n  p a p er f or m at, it  will sl o w t h e 
s p e e d at  w hi c h  w e  c a n  c o m pl et e  c ert ai n  st e ps i n tr a ns a cti o ns  wit h  y o u  a n d  d eli v eri n g s er vi c es t o 
y o u  b e c a us e  w e  will  n e e d  first t o s e n d t h e r e q uir e d  n oti c es  or dis cl os ur es  t o  y o u i n  p a p er f or m at, 
a n d t h e n  w ait  u ntil  w e r e c ei v e  b a c k fr o m  y o u  y o ur  a c k n o wl e d g m e nt  of  y o ur r e c ei pt  of s u c h 
p a p er  n oti c es  or  dis cl os ur es.  F urt h er,  y o u  will  n o l o n g er  b e  a bl e t o  us e t h e  D o c u Si g n s yst e m t o 
r e c ei v e r e q uir e d  n oti c es a n d  c o ns e nts  el e ctr o ni c all y  fr o m  us  or t o si g n  el e ctr o ni c all y  d o c u m e nts 
fr o m  us. 
 
 
All  n oti c es  a n d  dis cl os u r es  will  b e  s e nt t o  y o u el e ct r o ni c all y  


 
U nl ess  y o u t ell  us  ot h er wis e i n  a c c or d a n c e  wit h t h e  pr o c e d ur es  d es cri b e d  h er ei n,  w e  will  pr o vi d e 
el e ctr o ni c all y t o  y o u t hr o u g h t h e  D o c u Si g n s yst e m  all r e q uir e d  n oti c es,  dis cl os ur es, 
a ut h ori z ati o ns,  a c k n o wl e d g e m e nts,   a n d  ot h er  d o c u m e nts t h at ar e  r e q uir e d t o  b e  pr o vi d e d  or m a d e 
a v ail a bl e t o  y o u  d uri n g t h e  c o urs e  of  o ur r el ati o ns hi p  wit h  y o u.  T o r e d u c e t h e  c h a n c e  of  y o u 
i n a d v ert e ntl y  n ot r e c ei vi n g  a n y  n oti c e  or  dis cl os ur e,  w e  pr ef er t o  pr o vi d e  all  of t h e r e q uir e d 
n oti c es  a n d  dis cl os ur es t o  y o u  b y t h e s a m e  m et h o d  a n d t o t h e s a m e  a d dr ess t h at  y o u  h a v e  gi v e n 
us.  T h us,  y o u  c a n  r e c ei v e  all t h e  dis cl os ur es  a n d  n oti c es el e ctr o ni c all y   or i n  p a p er f or m at t hr o u g h 
t h e  p a p er  m ail  d eli v er y s yst e m. If  y o u  d o  n ot  a gr e e  wit h t his  pr o c ess,  pl e as e l et  us  k n o w  as 
d es cri b e d  b el o w.  Pl e as e  als o s e e  t h e  p ar a gr a p h i m m e di at el y  a b o v e t h at  d es cri b es t h e 
c o ns e q u e n c es  of  y o ur  el e cti n g  n ot t o r e c ei v e  d eli v er y  of t h e  n oti c es  a n d  dis cl os ur es 
el e ctr o ni c all y fr o m  us.  
 
 
H o w  t o  c o nt a ct  S a g e T h e r a p e uti cs  - P a rt  1 1:  
 
Y o u  m a y  c o nt a ct   us t o l et  us  k n o w  of  y o ur  c h a n g es as  t o  h o w w e  m a y   c o nt a ct  y o u el e ctr o ni c all y, 
t o r e q u est  p a p er  c o pi es  of  c ert ai n i nf or m ati o n fr o m  us,  a n d t o  wit h dr a w  y o ur  pri or  c o ns e nt t o 
r e c ei v e  n oti c es  a n d  dis cl os ur es  el e ctr o ni c all y  as f oll o ws: 
T o  c o nt a ct  us   b y e m ail  s e n d m ess a g es  t o: m ar c el @s a g er x. c o m  
 
 
T o   a d vis e  S a g e T h e r a p e uti cs  - P a rt   1 1  of  y o u r n e w  e m ail  a d d r ess  
 
T o  l et  us  k n o w  of  a  c h a n g e i n  y o ur e m ail  a d dr ess  w h er e  w e  s h o ul d s e n d  n oti c es  a n d dis cl os ur es 
el e ctr o ni c all y t o  y o u,  y o u  m ust s e n d  a n  e m ail  m ess a g e t o  us  at  m ar c el @s a g er x. c o m   a n d i n t h e 
b o d y  of  s u c h r e q u est y o u   m ust st at e:  y o ur  pr e vi o us e m ail  a d dr ess,  y o ur  n e w  e m ail  a d dr ess.   W e 
d o  n ot r e q uir e  a n y  ot h er i nf or m ati o n fr o m  y o u t o  c h a n g e  y o ur  e m ail  a d dr ess. 
 
If  y o u cr e at e d   a  D o c u Si g n  a c c o u nt,  y o u m a y   u p d at e it wit h   y o ur  n e w e m ail  a d dr ess  t hr o u g h  y o ur 
a c c o u nt  pr ef er e n c es.  
 
 
T o  r e q u est  p a p e r  c o pi es  f r o m  S a g e T h e r a p e uti cs  - P a rt  1 1  
 
T o r e q u est  d eli v er y fr o m  us  of  p a p er  c o pi es  of t h e  n oti c es  a n d  dis cl os ur es  pr e vi o usl y  pr o vi d e d 
b y  us t o  y o u  el e ctr o ni c all y,  y o u  m ust  s e n d  us a n  e m ail  t o m ar c el @s a g er x. c o m   a n d i n t h e  b o d y  of 
s u c h r e q u est  y o u  m ust st at e  y o ur  e m ail  a d dr ess, f ull  n a m e,  m aili n g  a d dr ess,  a n d t el e p h o n e 
n u m b er.  W e  will  bill  y o u f or  a n y f e es  at t h at ti m e, i f  a n y. 
 
 
T o  wit h d r a w   y o u r c o ns e nt  wit h  S a g e  T h e r a p e uti cs  - P a rt  1 1  
 
T o  i nf or m us  t h at  y o u  n o l o n g er wis h  t o r e c ei v e f ut ur e n oti c es   a n d  dis cl os ur es i n el e ctr o ni c 
f or m at  y o u  m a y: 


 
i. d e cli n e  t o si g n  a  d o c u m e nt fr o m wit hi n   y o ur si g ni n g s essi o n, a n d   o n t h e s u bs e q u e nt  p a g e, 
s el e ct t h e  c h e c k- b o x i n di c ati n g  y o u  wis h t o  wit h dr a w  y o ur  c o ns e nt,  or  y o u  m a y; 
 
ii. s e n d  us  a n  e m ail t o m ar c el @s a g er x. c o m   a n d i n t h e  b o d y  of s u c h r e q u est  y o u  m ust st at e  y o ur 
e m ail,  f ull n a m e,  m aili n g  a d dr ess,   a n d t el e p h o n e  n u m b er. W e   d o  n ot n e e d   a n y  ot h er i nf or m ati o n 
fr o m  y o u t o  wit h dr a w  c o ns e nt..   T h e  c o ns e q u e n c es  of  y o ur  wit h dr a wi n g  c o ns e nt f or  o nli n e 
d o c u m e nts  will  b e t h at tr a ns a cti o ns  m a y t a k e  a l o n g er ti m e t o  pr o c ess..  
 
 
R e q ui r e d   h a r d w a r e a n d  s oft w a r e 
 
T h e  mi ni m u m  s yst e m r e q uir e m e nts  f or  usi n g t h e  D o c u Si g n s yst e m m a y   c h a n g e  o v er ti m e. T h e 
c urr e nt  s yst e m r e q uir e m e nts ar e  f o u n d h er e:  htt ps://s u p p ort. d o c usi g n. c o m/ g ui d es/si g n er- g ui d e-  
si g ni n g-s yst e m-r e q uir e m e nts. 
 
 
A c k n o wl e d gi n g   y o u r a c c ess  a n d  c o ns e nt  t o r e c ei v e  a n d  si g n d o c u m e nts  el e ct r o ni c all y  
 
T o  c o nfir m t o  us t h at  y o u  c a n  a c c ess t his i nf or m ati o n  el e ctr o ni c all y,  w hi c h  will  b e si mil ar t o 
ot h er  el e ctr o ni c   n oti c es a n d  dis cl os ur es  t h at w e  will   pr o vi d e t o  y o u, pl e as e   c o nfir m t h at  y o u  h a v e 
r e a d t his  E R S D,  a n d (i) t h at  y o u  ar e  a bl e t o  pri nt  o n  p a p er  or el e ctr o ni c all y s a v e t his  E R S D f or 
y o ur f ut ur e  r ef er e n c e a n d  a c c ess;  or (ii) t h at  y o u  ar e  a bl e t o  e m ail t his  E R S D t o  a n  e m ail  a d dr ess 
w h er e  y o u  will  b e  a bl e t o  pri nt  o n  p a p er  or s a v e it f or  y o ur f ut ur e r ef er e n c e  a n d  a c c ess.  F urt h er, 
if  y o u  c o ns e nt t o r e c ei vi n g  n oti c es  a n d  dis cl os ur es  e x cl usi v el y i n  el e ctr o ni c f or m at  as  d es cri b e d 
h er ei n, t h e n s el e ct t h e  c h e c k - b o x  n e xt t o ‘I a gr e e t o  us e  el e ctr o ni c r e c or ds  a n d si g n at ur es’  b ef or e 
cli c ki n g ‘ C O N TI N U E’  wit hi n t h e  D o c u Si g n s yst e m.  
 
B y  s el e cti n g t h e c h e c k -b o x   n e xt t o ‘I a gr e e  t o  us e el e ctr o ni c  r e c or ds  a n d si g n at ur es’,  y o u c o nfir m 
t h at: 
 
•  
Y o u  c a n  a c c ess   a n d r e a d t his El e ctr o ni c  R e c or d  a n d   Si g n at ur e Dis cl os ur e;  a n d  
•  
Y o u  c a n   pri nt  o n  p a p er t his El e ctr o ni c  R e c or d  a n d   Si g n at ur e Dis cl os ur e,   or s a v e  or s e n d 
t his  El e ctr o ni c  R e c or d  a n d  Dis cl os ur e t o  a l o c ati o n  w h er e  y o u  c a n  pri nt it, f or f ut ur e 
r ef er e n c e  a n d  a c c ess;  a n d 
•  
U ntil   or  u nl ess  y o u  n otif y S a g e  T h er a p e uti cs  - P art   1 1 as  d es cri b e d   a b o v e,  y o u  c o ns e nt t o 
r e c ei v e  e x cl usi v el y t hr o u g h  el e ctr o ni c  m e a ns  all n oti c es,  dis cl os ur es,  a ut h ori z ati o ns, 
a c k n o wl e d g e m e nts,  a n d  ot h er  d o c u m e nts t h at  ar e r e q uir e d t o  b e  pr o vi d e d  or  m a d e 
a v ail a bl e t o  y o u  b y  S a g e  T h er a p e uti cs -  P art  1 1  d uri n g t h e  c o urs e  of  y o ur r el ati o ns hi p 
wit h  S a g e  T h er a p e uti cs  -  P art  1 1.