A Phase 2, Randomized, Double-blinded Study to Assess the Safety, Tolerability, and Efficacy of KarXT in Hospitalized Adults With DSM-5 Schizophrenia
Phase: PHASE2
Conditions: Schizophrenia
Sponsor: Karuna Therapeutics, Inc., a Bristol Myers Squibb company

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A Phase 2, Randomized, Double-blinded Study to Assess the Safety, 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 2 of 127
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13 Dec 2018 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 4 of 127
3
SYNOPSIS 
Protocol Number: 
KAR-004
Title: 
A Phase 2, Randomized, Double-blinded Study to Assess the Safety, Tolerability, and Efficacy of KarXT 
in Hospitalized Adults with DSM-5 Schizophrenia 
Investigational Product:
KarXT 
Study Centers: 
Approximately 12 study centers in the United States
Phase: 
Phase 2 
Objectives: 
Primary objective: 
The primary objective of the study is to assess the efficacy of KarXT (a fixed combination of xanomeline 
and trospium chloride) (xanomeline 125 mg/trospium 30 mg twice daily [BID]) versus placebo in 
reducing Positive and Negative Syndrome Scale (PANSS) total scores in adult inpatients with a 
Diagnostic and Statistical Manual‒Fifth Edition (DSM-5) diagnosis of schizophrenia. 
Secondary objectives:  
The secondary objectives of the study are to assess overall safety and tolerability of KarXT in adult 
inpatients with a DSM-5 diagnosis of schizophrenia: 
x
To assess spontaneously reported adverse events (AEs) in subjects treated with KarXT versus 
placebo 
x
To assess spontaneously reported cholinergic symptoms in subjects treated with KarXT versus 
placebo 
x
To assess orthostatic vital signs in subjects treated with KarXT versus placebo 
x
To assess electrocardiogram (ECG) parameters in subjects treated with KarXT versus placebo 
x
To assess reduction of PANSS positive score in subjects treated with KarXT versus placebo 
x
To assess reduction of PANSS Marder Factor score in subjects treated with KarXT versus 
placebo 
x
To assess the pharmacokinetics (PK) of xanomeline and trospium following administration of 
KarXT in adult subjects with a DSM-5 diagnosis of schizophrenia 
x
To assess Clinical Global Impression-Severity (CGI-S) results in subjects with KarXT versus 
placebo 
Study Design: 
The study will be an inpatient study in adult subjects with DSM-5 schizophrenia. Subjects will be 
randomized to receive either placebo or KarXT (xanomeline 125 mg/trospium 30 mg BID) for a treatment 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 5 of 127
period of 5 weeks. Subjects will start on a lead-in dose of xanomeline 50 mg/trospium 20 mg 2 times per 
day (BID) for the first 2 days followed by xanomeline 100 mg/trospium 20 mg BID for the remainder of 
Week 1 (Days 3 to 7). On Day 8, dosing will be titrated upwards to xanomeline 125 mg/trospium 30 mg 
BID unless the subject is continuing to experience AEs from the previous dose increase of xanomeline 
100 mg/trospium 20 mg BID. All subjects who were increased to xanomeline 125 mg/trospium 30 mg 
BID, depending on clinical response and tolerability, will have the option to return to xanomeline 
100 mg/trospium 20 mg BID for the remainder of the treatment period. Dosing must not change after 
Visit 7 of the study and may be decreased for tolerability reasons no more than once during the study.
Number of Subjects:  
A total of approximately 180 subjects planned to be randomized in a 1:1 ratio to either KarXT or placebo. 
Treatment: 
x
Fixed dose Xanomeline 50 mg/Trospium 20 mg BID, oral 
x
Fixed dose Xanomeline 100 mg/Trospium 20 mg BID oral 
x
Fixed dose Xanomeline 125 mg/Trospium 30 mg BID oral 
x
Matching placebo BID oral 
Study Duration: 
Total study duration is up to 7 weeks, including a 7-day screening phase (up to a 7-day extension of the 
screening phase is allowed, if necessary) and a 5-week treatment period. 
Inclusion Criteria: 
1.
Subject is aged 18-60 years, inclusive, at screening. 
2.
Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric 
evaluation based on the DSM-5 (American Psychiatric Association 2013) criteria and confirmed 
by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder 
Studies (MINI) version 7.0.2. 
3.
Subject is experiencing an acute exacerbation or relapse of symptoms, with onset less than 
2 months before screening. 
a.
The subject requires hospitalization for this acute exacerbation or relapse of symptoms. 
b.
If already an inpatient at screening, has been hospitalized for less than 2 weeks for the 
current exacerbation at the time of screening. 
4.
Positive and Negative Syndrome Scale total score between 80 and 120, inclusive. 
a.
Score of ≥4 (moderate or greater) for ≥ 2 of the following Positive Scale (P) items: 
i.
Item 1 (P1; delusions) 
ii.
Item 2 (P2; conceptual disorganization) 
iii.
Item 3 (P3; hallucinatory behavior) 
iv.
Item 6 (P6; suspiciousness/persecution) 
5.
There should not be a change (improvement) in PANSS total score between screening and 
baseline of more than 20%. 
6.
Subject will have been off lithium therapy for at least 2 weeks before baseline and free of all oral 
antipsychotic medications for at least 2 weeks before baseline. 
7.
Subjects taking a depot antipsychotic could not have received a dose of medication for at least 
1 and a half injection cycles before baseline (eg, 3 or more weeks off for a 2-week cycle). 
8.
Subject is capable of providing informed consent. 
a.
A signed informed consent form must be provided before any study assessments are 
performed. 
b.
Subject must be fluent (oral and written) in English to consent 
9.
Subject is willing and able to be confined to an inpatient setting for the study duration, follow 
instructions, and comply with the protocol requirements. 
10. Subject has a CGI-S score of ≥ 4 at screening and baseline visits. 
11. Body mass index (BMI) must be ≥18 and ≤ 40 kg/m2. 
12. Subject resides in a stable living situation and is anticipated to return to that same stable living 
situation after discharge, in the opinion of the investigator. 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 6 of 127
13. Both females of child-bearing potential and males with partners of child-bearing potential must 
be willing to use a double-barrier method of birth control (ie, any double combination of male or 
female condom with spermicidal gel, diaphragm, sponge, or cervical cap with spermicidal gel) 
during the study and for 7 days after the last dose of study drug.  
14. Subject has an identified reliable informant. An informant is needed at the screening and 
baseline visits as well as at the end of the study for relevant assessments. (Site staff may act as 
informant while the subject is an inpatient.) An informant may not be necessary if the subject has 
been the patient of the investigator for ≥ 1 year.
Exclusion Criteria 
1. Any primary DSM-5 disorder other than schizophrenia within 12 months before screening 
(confirmed using MINI version 7.0.2 at screening). 
2. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, 
gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any 
other condition that, in the opinion of the investigator, would jeopardize the safety of the subject 
or the validity of the study results, to exclude patients with human immunodeficiency virus 
(HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral 
infections based on the liver function test results. 
3. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma. 
4. History of irritable bowel syndrome (with or without constipation) or serious constipation 
requiring treatment within the last 6 months 
5. Has a DSM-5 diagnosis of moderate to severe substance abuse disorder (except tobacco use 
disorder) within the 12 months before screening (confirmed using MINI version 7.0.2 at 
screening), or current abuse as determined by urine toxicology screen or alcohol test. A
screening subject with mild substance abuse disorder within the 12 months before screening 
must be discussed and agreed upon with the medical monitor before he/she can be allowed into 
the study. Use of cannabis at screening will result in screen failure with the allowance to 
rescreen at a later date if no moderate to severe substance use disorder is determined. 
6. Risk for suicidal behavior during the study as determined by the investigator’s clinical assessment 
and Columbia Suicide Severity Rating Scale (C-SSRS) as confirmed by the following: 
a.
Answers “Yes” on items 4 or 5 (C-SSRS – ideation) with the most recent episode 
occurring within the 2 months before screening, or answers “Yes” to any of the 5 items 
(C-SSRS-behavior) with an episode occurring within the 12 months before screening. 
Nonsuicidal self-injurious behavior is not exclusionary. 
7.
Clinically significant abnormal finding on the physical examination, medical history, ECG, or 
clinical laboratory results at screening. 
8. Subjects cannot currently (within 2 weeks of baseline) be receiving oral antipsychotic medications, 
MAO inhibitors, anticonvulsants (eg, lamotrigine, Depakote), tricyclic antidepressants (eg,
imipramine, desipramine), selective serotonin reuptake inhibitors, or any other psychoactive 
medications except for as needed anxiolytics (eg, lorazepam, chloral hydrate). 
9. Pregnant, lactating, or less than 3 months postpartum. Sperm donation is not allowed for 90 days 
after the final dose of study drug. 
10. If, in the opinion of the investigator (and/or Sponsor), subject is unsuitable for enrollment in the 
study or subject has any finding that, in the view of the investigator (and/or Sponsor), may 
compromise the safety of the subject or affect their ability to adhere to the protocol visit 
schedule or fulfill visit requirements.
11. Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) during the 
90 days before screening. 
12. Subject has a history of treatment resistance to schizophrenia medications defined as failure to 
respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose 
per the label) or required clozapine within the last 12 months. 
13. Risk of violent or destructive behavior. 
14. Current involuntary hospitalization or incarceration. 
15. Participation in another clinical study in which the subject received an experimental or 
investigational drug agent within 3 months of screening. 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 7 of 127
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KAR-004 Amendment 3 
Version 4.0 
Page 8 of 127
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 9 of 127
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 10 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 11 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 12 of 127 
5
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation
Definition
AE
adverse event
AESI
adverse event of special interest
AIMS
Abnormal Involuntary Movement Scale
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the plasma concentration-time curve
BID
twice daily
BMI
body mass index
CFR
Code of Federal Regulations
CGI-S
Clinical Global Impression‒Severity
C-SSRS
Columbia-Suicide Severity Rating Scale
DILI
drug-induced liver injury 
DSM-5
Diagnostic and Statistical Manual‒Fifth Edition
EDC
electronic data capture
ECG
electrocardiogram
eCRF
electronic case report form
ET
early termination
FDA
US Food and Drug Administration
GCP
Good Clinical Practice
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council on Harmonisation
IEC
Independent Ethics Committee
IRB
Institutional Review Board
IWRS
interactive web response system
MCC
microcrystalline cellulose
MINI
Mini International Neuropsychiatric Interview
MMRM
mixed model for repeated measures
PANSS
Positive and Negative Syndrome Scale
PK
pharmacokinetic
SAE
serious adverse event
SAP
statistical analysis plan
SUSAR
suspected unexpected serious adverse reaction
ULN
upper limit of the normal range

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 13 of 127 
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INTRODUCTION
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(or other indications such as Alzheimer’s disease) KDVEHHQRXWZHLJKHGE\WKH
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 14 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 17 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 20 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 21 of 127 
7
STUDY OBJECTIVES AND ENDPOINTS 
7.1
Objectives 
7.1.1
Primary Objective 
The primary objective of the study is to assess the efficacy of KarXT (a fixed 
combination of xanomeline and trospium chloride; xanomeline 125 mg/trospium 
30 mg) versus placebo in reducing PANSS total score in adult inpatients with a 
Diagnostic and Statistical Manual‒Fifth Edition (DSM-5) diagnosis of schizophrenia. 
7.1.2
Secondary Objectives 
The secondary objectives of the study are to assess overall safety and tolerability of 
KarXT in adult inpatients with a DSM-5 diagnosis of schizophrenia: 
x
To assess spontaneously reported AEs in subjects treated with KarXT versus 
placebo 
x
To assess spontaneously reported cholinergic symptoms in subjects treated with 
KarXT versus placebo 
x
To assess orthostatic vital signs in subjects treated with KarXT versus placebo 
x
To assess ECG parameters in subjects treated with KarXT versus placebo 
x
To assess reduction of PANSS positive score in subjects treated with KarXT 
versus placebo 
x
To assess reduction of PANSS Marder Factor score in subjects treated with 
KarXT versus placebo 
x
To assess the pharmacokinetics (PK) of xanomeline and trospium following 
administration of KarXT in adult subjects with a DSM-5 diagnosis of 
schizophrenia 
x
To assess Clinical Global Impression‒Severity (CGI-S) scale results in subjects 
with KarXT versus placebo 
7.2
Endpoints 
7.2.1
Primary Endpoint 
x
Change in PANSS total score at Week 5 
7.2.2
Secondary Endpoints
x
Efficacy Endpoints: 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 22 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 23 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 24 of 127 
An Independent Safety Monitoring Committee (ISMC) will be responsible for 
reviewing on a periodic basis the safety data from this study and confirming that the 
study may continue. 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 25 of 127 
8.1.1
Study Design 
Phase:
Screening
Inpatient Treatment
End of 
Treatment
Day:
Day -7 to -1
Day 1
Day 3 ± 1 
day
Day 7 ± 2 
days
Day 8 ± 2
days
Day 14 ± 2 
days
Day 21 ± 2 
days
Day 28 ± 2 
days
Day 35 −2
days
Visit:
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Xanomeline/ 
trospium 
(KarXT):
N/A
50 mg/20 
mg BID
100 mg/20 
mg BID
100 mg/20 
mg BID
125 mg/30 
mg BID
(Option: 100 
mg/20 mg 
BID)a
125 mg/30 
mg BID
(Option: 100 
mg/20 mg 
BID)a
125 mg/30 
mg BID
(Option: 100 
mg/20 mg 
BID)a
125 mg/30 
mg BID
(Option: 100 
mg/20 mg 
BID)b
N/A
Comment:
Up to a 7-day 
extension to 
the screening 
phase is 
allowed.
2-day lead-
in dose
Upward 
titration of 
dose
Upward 
titration of
dose
Downward dose adjustment 
allowed according to clinical 
response/tolerability
No dose adjustment allowed 
(after Day 21)
BID = twice daily. 
a 
All subjects who were increased to xanomeline 125 mg/trospium 30 mg, depending on clinical response and tolerability, will have the option to return to 
xanomeline 100 mg/trospium 20 mg BID for the remainder of the treatment period. 
b 
No dose adjustment will be allowed after Visit 7. All subjects will continue taking the doses chosen for xanomeline and trospium at Visit 7. 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 26 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 27 of 127 
7DEOH
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 28 of 127 
PROCEDURE 
SCREENING 
PHASE 
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TO -1)a 
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&&,

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 29 of 127 
K
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 30 of 127 

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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 31 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 32 of 127 
2. 
The investigator will be provided with a Study Site Binder for storing study 
related regulatory and study site documentation; eg, study logs and forms. 
3. 
The investigator must review all eCRF entries for completeness and accuracy.  
4. 
Periodic monitoring visits will be conducted on a regular basis by the Sponsor or 
designee in order to verify the accuracy of data entered on each eCRF against the 
raw data from source documents at the site. Items needing correction/clarification 
will be identified and brought to the attention of the study site personnel and 
principal investigator, and corrections will be made as appropriate. 
5.  
The Sponsor or designee will perform a final review and data management of the 
eCRF. The study database will be validated using appropriate validation processes. 
6. 
The Sponsor or designee may perform a regulatory audit of the study site, and 
may include a complete review of the overall study conduct, regulatory 
documentation, and selected subject eCRFs and source documents. 
8.3
Selection of Study Population 
8.3.1
Number of Planned Subjects  
A total of approximately 180 study subjects and approximately 12 sites in the United 
States are planned. Subjects who are randomized into the double-blind treatment phase 
but discontinue or withdraw will not be replaced. 
8.3.2
Inclusion Criteria 
To be eligible for enrollment, subjects must satisfy all of the following criteria: 
Subject is aged 18-60 years, inclusive, at screening. 
1.
Subject has a primary diagnosis of schizophrenia established by a comprehensive 
2.
psychiatric evaluation based on the DSM-5 (American Psychiatric Association 
2013) criteria and confirmed by Mini International Neuropsychiatric Interview for 
Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2. 
Subject is experiencing an acute exacerbation or relapse of symptoms, with onset 
3.
less than 2 months before screening. 
a.
The subject requires hospitalization for this acute exacerbation or relapse of 
symptoms. 
b. If already an inpatient at screening, has been hospitalized for less than 2 weeks 
for the current exacerbation at the time of screening. 
Positive and Negative Syndrome Scale total score between 80 and 120, inclusive, at 
4.
screening. 
a.
Score of ≥4 (moderate or greater) for ≥ 2 of the following Positive Scale (P) 
items at screening: 
i. Item 1 (P1; delusions) 
ii. Item 2 (P2; conceptual disorganization) 
iii. Item 3 (P3; hallucinatory behavior) 
iv. Item 6 (P6; suspiciousness/persecution) 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 33 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 34 of 127 
Has a DSM-5 diagnosis of moderate to severe substance abuse disorder (except 
5.
tobacco use disorder) within the 12 months before screening (confirmed using MINI 
version 7.0.2 at screening), or current abuse as determined by urine toxicology 
screen or alcohol test. A screening subject with mild substance abuse disorder 
within the 12 months before screening must be discussed and agreed upon with the 
medical monitor before he/she can be allowed into the study. Use of cannabis at 
screening will result in screen failure with the allowance to rescreen at a later date if 
no moderate to severe substance use disorder is determined. 
Risk for suicidal behavior during the study as determined by the investigator’s
6.
clinical assessment and the C-SSRS as confirmed by the following: 
a.
Answers “Yes” on items 4 or 5 (C-SSRS – ideation) with the most recent 
episode occurring within the 2 months before screening, or answers “Yes” to 
any of the 5 items (C-SSRS-behavior) with an episode occurring within the 
12 months before screening. Nonsuicidal self-injurious behavior is not 
exclusionary.
Clinically significant abnormal finding on the physical examination, medical history, 
7.
ECG, or clinical laboratory results at screening. 
Subjects cannot currently (within 2 weeks of baseline) be receiving oral 
8.
antipsychotic medications, MAO inhibitors, anticonvulsants (eg, lamotrigine, 
Depakote), tricyclic antidepressants (eg, imipramine, desipramine), selective 
serotonin reuptake inhibitors, or any other psychoactive medications except for 
anxiolytics (eg, lorazepam, chloral hydrate) taken as needed.  
Pregnant, lactating, or less than 3 months postpartum. Sperm donation is not 
9.
allowed for 90 days after the final dose of study drug. 
If, in the opinion of the investigator (and/or Sponsor), subject is unsuitable for 
10.
enrollment in the study or subject has any finding that, in the view of the 
investigator (and/or Sponsor), may compromise the safety of the subject or affect 
their ability to adhere to the protocol visit schedule or fulfill visit requirements. 
Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) 
11.
during the 90 days before screening. 
Subject has a history of treatment resistance to schizophrenia medications defined as 
12.
failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeks 
at an adequate dose per the label) or required clozapine within the last 12 months. 
Risk of violent or destructive behavior. 
13.
Current involuntary hospitalization or incarceration. 
14.
Participation in another clinical study in which the subject received an experimental 
15.
or investigational drug agent within 3 months of screening. 
8.3.4
Removal of Subjects from Therapy or Assessments 
The availability of any new adverse safety information related to KarXT may result in 
stopping the study. An investigator, Sponsor, or Institutional Review Board (IRB) may 
take such actions. If the study is terminated for safety reasons, subjects will be notified 
immediately and assured that appropriate treatment and follow-up will be available. If 
an investigator terminates the study, the Sponsor, subjects, and IRB will be informed 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 35 of 127 
about the reason for such action. Similarly, if the Sponsor terminates the study, it will 
inform the investigators, the IRB, and the subjects of the reason for such an action. 
Similar notifications will be sent by the IRB if it takes such an action. 
8.3.5
Subject Withdrawal 
Subjects who are randomized into the double-blind treatment phase but then discontinue 
or withdraw will not be replaced.  
Subjects may withdraw from the study at any time as stated in the ICF (given to the 
subject at the time of enrollment) and without prejudice to further treatment. Subjects 
may be withdrawn or be discontinued from the study by the study investigator or the 
Sponsor for the following reasons: 
1. 
Violation of entry criteria; ie, subjects who are enrolled but are later discovered 
not to meet entry criteria 
2. 
Adverse event(s) 
3. 
Protocol noncompliance (eg, if a study subject is off study drug for >5 days in a 
row). 
4. 
Pregnancy (females of childbearing potential). Any study subject who becomes 
pregnant while participating in the study will be unblinded to study treatment 
randomization. If she is found to be on active treatment assignment, she will be 
followed until her pregnancy reaches term. 
5. 
Development of suicidal or assaultive behavior 
6. 
Alcohol or illegal drug use 
7. 
Development of an intercurrent systemic illness requiring significant medical 
intervention or a clinically significant change in laboratory testing as per the 
investigator. 
8.
Sponsor’s decision to discontinue study
9. 
Subject withdraws consent 
10. 
Subject has need for a medication prohibited by the protocol. 
Subjects withdrawing from the study will be encouraged to complete the same final 
evaluations as subjects completing the study according to this protocol, particularly 
safety evaluations. The aim is to record data in the same way as for subjects who 
completed the study. 
Reasonable efforts will be made to contact subjects who leave the unit or are lost to 
follow-up. These efforts must be documented in the subject’s file. Subjects with AEs 
ongoing at end of study will be followed until the AE is resolved or the subject is 
considered to be in stable condition. 
The Sponsor has the right to terminate the study at any time in case of SAEs or if 
special circumstances concerning the study drug become known, making further 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 36 of 127 
treatment of subjects impossible. In this event, the investigator(s) will be informed of 
the reason for study termination. 
The reason for withdrawal or discontinuation must be recorded on the subject’s eCRFs. 
If a subject discontinues the study prematurely, for any reason, all procedures that 
would have been completed at the study discharge should be performed before subject 
study discontinuation, and the termination eCRF is to be completed. 
All subjects withdrawn from the study because of an emergent adverse experience will 
continue to be followed until the AE(s) resolve or stabilize. 
Pregnancy 
No evidence of mutagenicity, or treatment effects on reproduction, fertility, or fetal 
parameters have been demonstrated in animals following administration of xanomeline, 
but there are no adequate and well-controlled studies in pregnant women (FDA 
Pregnancy Category B). Animal reproduction studies of trospium chloride have shown 
an adverse effect on the fetus, but potential benefits may warrant the use of the drug in 
pregnant women despite the risk (FDA Pregnancy Category C).
Therefore, participation of women of childbearing potential in this study must be 
willing to use a double-barrier method of birth control (ie, any double combination of 
male or female condom with spermicidal gel, diaphragm, sponge, or cervical cap with 
spermicidal gel) during the study and for 7 days after the last dose of study drug. 
Females of childbearing potential will have a serum pregnancy test at screening and a 
urine pregnancy test on Day 1 (before receiving xanomeline and/or trospium) and 
Day 35. Should a woman become pregnant or suspects she is pregnant while 
participating in this study, she should inform study staff and her primary care physician 
immediately. 
Definition of women of childbearing potential: For the purpose of this study, a woman 
is considered of childbearing potential following menarche and until confirmed post-
menopausal state, unless permanently sterile. Permanent sterilization methods include 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.  
Pregnant women are excluded from this study because the effects of xanomeline and 
trospium on the developing human fetus are unknown with the potential for teratogenic
or abortifacient effects.   
Because there is an unknown but potential risk for AEs in nursing infants secondary to 
treatment of the mother with xanomeline or trospium, women who are breastfeeding 
must not be enrolled in the study. 
The effects of study drug on sperm are unknown. Men who agree to enroll in the study 
must agree to use a double-barrier method of birth control (ie, any double combination 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 37 of 127 
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13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 38 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 39 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 40 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 41 of 127 
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and the Sponsor’s medical monitor will be blinded to the subject treatment assignment. 
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&&,

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 42 of 127 
If unblinding is necessary for the welfare of a subject who has experienced an AE, 
unblinding of study drug may occur for just that subject. If an AE is thought to be 
related to the study drug and poses a safety risk, the investigator must decide whether to 
stop investigational treatment and/or treat the subject. Subject withdrawal should be 
avoided, if possible. If discontinuation of treatment occurs, every attempt should be 
made to restart study drug if medically appropriate, whatever the duration of 
discontinuation. When a subject has an AE that requires that the investigator be 
unblinded, the investigator can obtain the treatment assignment from the IWRS system. 
The site is expected to notify the study medical monitor before breaking the study blind, 
unless it is in the subject’s best interest if the blind is broken immediately. Note: in most 
circumstances it is not necessary to unblind a subject, even if an SAE has occurred. For 
many drugs there is no specific therapy for AEs. The appropriate course of action is to 
stop the investigational drug, and treat the signs and symptoms resulting from the AE. 
8.4.10 Prior and Concomitant Therapy 
8.4.10.1 Prior Medications 
Subjects will be asked for all prior medications he/she were taking up to 6 months 
before the study, up to the time of the first dose of study medication on Day 1. All prior 
medications will be recorded on the eCRF.  
8.4.10.2 Prohibited Medication/Therapy 
During the study (ie, from the time of enrollment at the screening visit until study 
completion), subjects will refrain from the use of any new concomitant medications 
without the specific prior approval of the principal investigator. The administration of 
any other concomitant medications during the study period is prohibited without the 
prior approval of the principal investigator unless its use is deemed necessary in a 
medical emergency. Any medication taken by a subject during the course of the study 
and the reason for its use will be documented in the source documents and eCRF. 
Within 2 weeks of baseline, subjects could not have taken oral antipsychotic 
medications, MAO inhibitors, mood stabilizers (ie, lithium), anticonvulsants (eg, 
lamotrigine, Depakote), tricyclic antidepressants (eg, imipramine, desipramine), 
selective serotonin reuptake inhibitors, or any other psychoactive medications except for 
anxiolytics that were taken on an as needed basis (eg, lorazepam, chloral hydrate). 
Intramuscular antipsychotic medications taken before baseline should not have been 
taken within 1 and a half cycles from baseline (eg, 3 or more weeks off for a 2-week 
cycle). Please direct questions relating to prohibited medications to the assigned 
Medical Monitor. 
Subjects are not to have alcohol or illegal drug abuse within the prior 12 months of 
screening (unless medical monitor provided approval at screening), or at any time 
during the study.  

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 43 of 127 
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Note: Written informed consent (IC) must be obtained before performing any study-
related procedure, including screening evaluations. 
6FUHHQLQJVKRXOGEHSHUIRUPHGIURP'D\WR'D\7KHVFUHHQLQJSKDVHLVDOORZHG
WREHH[WHQGHGXSWRDQDGGLWLRQDOGD\VLIQHFHVVDU\
6WXG\FDQGLGDWHVZLOOEHVFUHHQHGWRDVVHVVHOLJLELOLW\IRUHQUROOPHQWLQWRWKHVWXG\$
VFUHHQLQJORJZLOOEHPDLQWDLQHGIRUDOOFRQVHQWHGVWXG\FDQGLGDWHV$VFUHHQIDLOXUHLV
DQ\VWXG\FDQGLGDWHZKRVLJQVWKH,&DQGKDVFRPSOHWHGWKHVFUHHQLQJHYDOXDWLRQEXW
GRHVQRWTXDOLI\IRUWKHVWXG\RUGLVFRQWLQXHVWKHVWXG\EHIRUHVWXG\HQUROOPHQW7KH
study candidate’s initLDOVGDWHVFUHHQHGDQGUHDVRQVIRUVFUHHQLQJIDLOXUHPXVWEH
UHFRUGHGRQWKHVFUHHQLQJORJ
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 44 of 127 
Review the study candidate’s medical DQGSV\FKLDWULFKLVWRU\ DQGSULRUDQG
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13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
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13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 47 of 127 
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13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 48 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 49 of 127 
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13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 50 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 51 of 127 
with the use of a medicinal (investigational) product, whether or not it is related to the 
medicinal (investigational) product. This includes an exacerbation of pre-existing 
conditions or events, intercurrent illnesses, drug interaction or the significant worsening 
of the indication under investigation that is not recorded elsewhere in the eCRF under 
specific efficacy assessments. Anticipated fluctuations of pre-existing conditions, 
including the disease under study that does not represent a clinically significant 
exacerbation or worsening need not be considered AEs. 
In accordance with the protocol, the investigator and/or clinic staff will elicit AEs and 
inter-current illness during and at the end of the study period and these will be recorded 
on the appropriate page of the eCRF. Adverse events will be elicited by asking the 
subject a nonleading question, for example, “Have you experienced any new or changed 
symptoms since we last asked?” The eCRF will be completed at the end of the study as 
soon as the results of the final lab tests are available.  
The reporting period for AEs is the period immediately following the administration of 
study product on Visit 2/Day 1 and up to the time of discharge (Visit 9/Day 35) of the 
subject from the study. 
Adverse events will be reported on the AE eCRF using a recognized medical term or 
diagnosis that accurately reflects the event. Adverse events will be assessed by the 
investigator for severity, relationship to the study product, possible etiologies and 
whether the event meets criteria as a SAE and therefore requires immediate notification 
of the Sponsor, the IRB, and the FDA. If the event has not resolved at the end of the 
study reporting period it will be documented as still present on the eCRF. If an AE 
evolves into a condition that becomes “serious” it will also be reported as an SAE. 
Assessment of Severity 
Each AE will be assigned a category by the investigator as follows: 
Mild:
An AE that is easily tolerated by the subject, causes minimal discomfort,
and does not interfere with everyday activities.
Moderate:
An AE that is sufficiently discomforting to interfere with normal 
everyday activities; intervention may be needed.
Severe:
An AE that prevents normal everyday activities; treatment or other 
intervention usually needed.
If there is a change in severity of an AE, it must be recorded as a separate event. 
Assessment of Causality 
Every effort will be made by the investigator to assess the relationship of the AE, if any, 
to the study drug. Causality should be assessed using the categories presented in the 
following table: 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 52 of 127 
Unrelated:
Clinical event with an incompatible time relationship to study drug
administration, and that could be explained by underlying disease or 
other drugs or chemicals or is incontrovertibly not related to the study 
drug.
Unlikely:
Clinical event whose time relationship to study drug administration 
makes a causal connection improbable, but that could plausibly be 
explained by underlying disease or other drugs or chemicals.
Possible:
Clinical event with a reasonable time relationship to study drug
administration, but that could also be explained by concurrent disease 
or other drugs or chemicals.
Probable:
Clinical event with a reasonable time relationship to study drug
administration, and is unlikely to be attributed to concurrent disease 
or other drugs or chemicals.
Very 
Likely/Certain:
Clinical event with plausible time relationship to study drug
administration, and that cannot be explained by concurrent disease or 
other drugs or chemicals.
Action Taken 
The investigator will describe the action taken in the appropriate section of the eCRF, as 
follows: 
x None 
x Study drug stopped 
x Study drug temporarily interrupted 
x Concomitant medication 
x Other, specify 
Follow-up of Adverse Events 
Subjects with AEs/SAEs will be treated if necessary and followed by the investigator 
until the event resolves or until, in the opinion of the investigator, the event is stabilized 
or determined to be chronic. The investigator will provide or arrange for appropriate 
follow-up (if required) for subjects, and document the course of the subject’s condition. 
Additional medical evaluation and treatment will be arranged as appropriate. Details of 
AE resolution must be documented in the eCRF. 
Documentation and Reporting of Adverse Events 
AEs should be reported and documented in accordance with the procedures outlined 
below. All AEs occurring during the study must be documented on the relevant eCRF 
pages. The following data should be documented for each AE: 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 53 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 54 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 55 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 56 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 57 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 58 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 59 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 60 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 61 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 62 of 127 
11.2 Analysis Populations 
11.2.1 Intent-To-Treat Population 
Intent-to-treat (ITT) population is defined as subjects who are randomized to the study. 
11.2.2 Modified Intent-To-Treat Population 
Modified Intent-to-treat (mITT) population is defined as randomized subjects who 
receive at least 1 dose of study drug and have a baseline assessment. The mITT 
population will be used for efficacy analyses. 
11.2.3 Safety Population 
Safety population is defined as subjects who receive at least 1 dose of study drug. The 
safety population will be used for safety analyses.
11.2.4 Pharmacokinetic Population 
Pharmacokinetic population is defined as randomized subjects who receive at least 
1 dose of study drug and have at least 1 measurable serum concentration of study 
medication. PK population will be used for PK analyses.
11.3 Statistical Analyses 
11.3.1 Subject Disposition  
The number of subjects in each analysis population and the reasons for discontinuation 
will be summarized. In addition, subjects’ status with regard to study treatment and 
follow-up will also be summarized. 
11.3.2 Demographic and Other Baseline Characteristics 
Subject disease and baseline characteristics will be summarized using frequency 
distribution or descriptive statistics as appropriate. 
11.3.3 Efficacy Analyses 
The primary endpoint of the study is the change from baseline in PANSS total score at 
Week 5. The difference between KarXT and placebo at Week 5 will be estimated using 
a mixed model for repeated measures (MMRM). The model will include the observed 
change from baseline PANSS total score at Week 2, Week 4, and Week 5 as the 
response. The treatment difference at Week 5 will be estimated using contrasts. The 
MMRM will include the treatment group (KarXT or placebo), visit, and the interaction 
between the treatment group and visit as fixed factors. Site, age, gender, and baseline 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 63 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 64 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 65 of 127 
x For the primary efficacy analysis, likelihood-based modeling approach will be 
used to handle incomplete data. For this purpose, an MMRM will be applied. 
x Sensitivity analysis for the primary efficacy endpoint will be conducted using the 
last observation carried forward approach. In this analysis, the missing values 
will be replaced by the previous visit PANSS total score carried forward.  
x
Sensitivity analysis for the primary efficacy endpoint will be conducted using the 
Multiple Imputation approach; ie, by replacing each missing value with a set of 
plausible values that represent the uncertainty about the right value to impute.  
11.4 Determination of Sample Size 
Assuming a PANSS total score difference of 9 between drug and placebo and standard 
deviation of 18, a sample size of approximately 180 (90 evaluable subjects per arm) will 
result in a power of 91% for a 2-sided alpha of 0.05. 
11.5 Protocol Deviations 
All protocol deviations will be tracked in the eCRF/electronic data capture (EDC) 
system. Deviations considered major will be identified as such before study unblinding
during medical monitor periodic review.
Major protocol deviations will be tabulated including the frequency and percentage of 
subjects with each type of deviation by treatment group. 
12 QUALITY ASSURANCE AND QUALITY CONTROL 
12.1 Audit and Inspection 
Study centers and study documentation may be subject to a Quality Assurance audit 
during the course of the study by the Sponsor or its nominated representative. In 
addition, inspections may be conducted by regulatory authorities at their discretion.
The study site personnel and principal investigator must make all study records 
(including source data and documentation) available to US and International regulatory 
agency personnel, the IRB and the study Sponsor or designee, for the purposes of 
monitoring, auditing, inspection, and copying. In addition, disclosure of study 
information to third parties may be required by law. 
12.2 Monitoring 
The study will be monitored by the Sponsor or its designee on a regular basis 
throughout the study period. Data for each subject will be recorded on an eCRF. Data 
collection must be completed for each subject who signs an ICF and is administered 
study drug. Some data such as scale assessments and laboratory results will be 
maintained in the vendor systems.  

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 66 of 127 
,QDFFRUGDQFHZLWKFXUUHQW*RRG&OLQLFDO3UDFWLFHF*&3DQG,QWHUQDWLRQDO&RXQFLOIRU
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The primary source document for this study will be the subject’s medical record. If 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 67 of 127 
13 RECORDS AND SUPPLIES 
13.1 Drug Accountability 
The accountability for the study drug at the study site rests with unblinded study 
monitors. These persons will maintain records of all the investigational products (drug 
and placebo), including their delivery and receipt, inventory at the site, use by each 
subject, and the destruction of unused study drug according to the directions of the 
Sponsor or designee. The investigators will assure that drug and placebo are used 
according to the protocol. The investigators will assure that the study drug and the 
records described in this paragraph will be stored in a locked area suitable for storage of 
pharmaceutical products, and in accordance with the conditions specified on the study 
drug label. Further, the investigators assure that the study drug and the records will be 
available for examination by the unblinded study monitor on periodic visits.  
All unused study drug supplies and equipment will be destroyed according to directions 
of the Sponsor or designee at the end of the study. 
On receipt of the study drug, an unblinded pharmacist at the study site will conduct an 
inventory of the supplies and verify that study drug supplies are received intact and in 
the correct amounts before completing a supplies receipt. The unblinded pharmacist will 
retain a copy of this receipt at the study center and it will be reviewed by the unblinded 
study monitor. The unblinded study monitor may check the study supplies at each study 
center at any time during the study.
It is the responsibility of the unblinded study monitor to ensure that the unblinded 
pharmacist has correctly documented the amount of the study drug received, dispensed, 
and returned on the dispensing log that will be provided. A full drug accountability log 
will be maintained at the study center at all times. The unblinded study monitor will also 
perform an inventory of study drug at the close-out visit to the study center. All
discrepancies must be accounted for and documented.

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 68 of 127 
14
ETHICS 
14.1 Independent Ethics Committee or Institutional Review Board 
The protocol, informed consent, and other written material given to the subjects, and 
any other relevant study documentation will be reviewed and approved by the governing 
IRB of the participating center before study initiation and/or before the study drug is 
released to the investigator, and the investigator will keep the IRB informed as to the 
progress of the study. 
Modifications or changes to the protocol, the informed consent, or other study 
documentation may not be initiated without prior written IRB approval except when 
necessary to eliminate immediate hazards to the subjects or when the change(s) involves 
only logistical or administrative aspects of the study. Such modifications will be 
submitted to the IRB and written verification that the modification was submitted 
should be obtained. 
The IRB must be informed by the principal investigator of informed consent changes or 
revisions of other documents originally submitted for review; serious and/or unexpected 
adverse experiences occurring during the study; new information that may affect 
adversely the safety of the subjects or the conduct of the study; an annual update and/or 
request for re-approval; and when the study has been completed. 
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and 
other records will be identified by a coded number and initials only; on some specimen 
collection records, the subject’s birth date may also appear. All study records will be 
kept in a locked file cabinet and code sheets linking a subject’s name to a subject 
identification number will be stored separately in another locked file cabinet. Clinical 
information will not be released without written permission of the subject, except as 
necessary for monitoring by the FDA or the Sponsor of the clinical study. 
14.2 Regulatory Authorities 
Relevant study documentation will be submitted to the US regulatory authorities, 
according to local/national requirements, for review and approval before the beginning 
of the study. On completion of the study, the regulatory authorities will be notified that 
the study has ended. 
14.3 Ethical Conduct of the Study 
The study will be conducted in accordance with the ethical principles set forth in the 
Declaration of Helsinki, the Guideline for GCP (ICH E6), the United States CFR 
governing the protection of human subjects (21CFR§50), IRBs (21CFR§56),  the 
requirements for conducting clinical investigations (21CFR§312), and all applicable 
local, state and federal government regulations and laws. 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
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14.4 Informed Consent 
Written informed consent must be obtained before any protocol-specified procedures or 
interventions are carried out. Subjects will be counseled about the study before giving 
their written informed consent. The investigator or designated personnel will inform the 
subject of the objectives, methods, anticipated benefits, potential risks, and 
inconveniences of the study. The subject should be given every opportunity to ask for 
clarification of any points s/he does not understand and, if necessary, ask for more 
information. Subjects must be given ample opportunity to inquire about details of the 
study. The process of obtaining informed consent must be in accordance with applicable 
regulatory requirement(s) and must adhere to GCP. 
The investigator will explain the nature of the study and will inform the subject that 
participation is voluntary and that they can withdraw at any time. Written informed 
consent will be obtained from each subject before entry into the study. A copy of the 
signed consent form will be given to every participant and the original will be 
maintained with the subject’s records. The Informed Consent should be translated and 
certified into the local language of the respondent, as deemed necessary.   
It should be emphasized that the subject may refuse to enter the study or to withdraw 
from the study at any time, without consequences for their further care or penalty or loss 
of benefits to which the subject is otherwise entitled. Subjects who refuse to give or who 
withdraw written informed consent should not be included or continue in the study. 
The consent form must be approved by the IRB and be acceptable to the Sponsor. 
Consent forms must be written so as to be understood by the prospective subject. 
Informed consent will be documented by the use of a written consent form approved by 
the IRB and signed and dated by the subject and by the person who conducted the 
informed consent discussion. The signature confirms the consent is based on 
information that has been understood. Each signed ICF must be kept on file by the 
investigator for possible inspection by Regulatory Authorities and/or the Sponsor or its 
designee. The subject should receive a copy of the signed and dated written ICF and any 
other written information provided to the subjects, and should receive copies of any 
signed and dated consent form updates and any amendments to the written information 
provided to subjects.  
If new information becomes available that may be relevant to the subject’s willingness 
to continue participation in the study, a new ICF will be approved by the IEC(s)/IRB(s) 
(and regulatory authorities, if required). The study subjects will be informed about this 
new information, and reconsent will be obtained. 
14.5 Conflict of Interest 
The investigators will be partially paid by the Sponsor of this study for the study related 
expenses, but they will not profit from results, either positive or negative, with regard to 

Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
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subjects’ identity will remain confidential.
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 71 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 72 of 127 
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13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 73 of 127 
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Karuna Pharmaceuticals 
13 Dec 2018 
KAR-004 Amendment 3 
Version 4.0 
Page 74 of 127 
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