Conditions: Pruritus Prurigo Nodularis Atopic Dermatitis Psoriasis
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 558
Healthy volunteers: no

Brief summary:
Study of the long term safety of serlopitant for the treatment of pruritus in adults.

Detailed description:

Arms:
arm 1: Serlopitant Tablets

Interventions: intervention 1: 5 mg Serlopitant Tablets
Intervention descriptions: intervention 1: Serlopitant Tablets

Protocol document:
Prot_000.pdf: 
Protocol: MTI-107 
Confidential - Proprietary Information 

Protocol number: MTI-107 

Document title: An open-label long-term safety study of serlopitant for the 
treatment of pruritus. 

Version numbers: Protocol Version 3.0 

Date of the documents: 21 March 2019 

NCT number: NCT03540160 


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CLINICAL STUDY PROTOCOL 
 
TITLE:  
AN OPEN-LABEL LONG-TERM SAFETY STUDY OF 
SERLOPITANT FOR THE TREATMENT OF PRURITUS  
IND No.: 
 
 
117780 
EudraCT: 
 
 
2017-004211-40 
ClinicalTrials.gov ID:  
TBD 
Protocol No.:  
 
MTI-107 
Protocol Version/Date: 
FINAL 1.0 18 December 2017 
Development Phase:  
Phase 3 
Sponsor: 
 
 
Menlo Therapeutics Inc. 
200 Cardinal Way, 2nd Floor 
Redwood City, CA 94063  
 
 
 
Confidentiality Statement: 
This document is a confidential communication of Menlo Therapeutics Inc. As such, the 
recipients agree not to disclose or reproduce, without prior written approval, this 
document and any attachments, except to appropriate Institutional Review Boards, Ethics 
Committees, representatives of the US Food and Drug Administration, the European 
Medicines Agency, other Competent Authorities or regulatory agencies, or as otherwise 
required by applicable laws or regulations. 
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SIGNATURE PAGE FOR INVESTIGATOR(S) 
 
TITLE:  
AN OPEN-LABEL LONG-TERM SAFETY STUDY OF 
SERLOPITANT FOR THE TREATMENT OF PRURITUS 
IND No.: 
 
 
117780 
EudraCT: 
 
 
2017-004211-40 
ClinicalTrials.gov ID:  
TBD 
Protocol No.:  
 
MTI-107 
Protocol Version/Date: 
FINAL 1.0 18 December 2017 
Development Phase:  
Phase 3 
Sponsor: 
 
 
Menlo Therapeutics Inc. 
200 Cardinal Way, 2nd Floor 
Redwood City, CA 94063  
 
 
I have read the protocol and agree to conduct this study in accordance with the protocol, all 
relevant laws and regulations in force at the time, International Conference on Harmonisation 
Guidelines for Good Clinical Practice, and the Declaration of Helsinki.  
 
 
 
Principal/Coordinating Investigator’s printed name 
 
 
 
 
 
 
Principal/Coordinating Investigator’s signature 
 
Date (DD-MMM-YYYY) 
 
  
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PROTOCOL SYNOPSIS 
Study Title: 
An Open-Label Long-Term Safety Study of Serlopitant for the Treatment of Pruritus  
Protocol Number: 
MTI-107 
Sponsor: 
Menlo Therapeutics Inc. 
Development Phase: 
Phase 3 
Study Objectives: 
Primary objective:  
• 
To assess the long-term safety of serlopitant in adults with pruritus 
associated with prurigo nodularis (PN), atopic dermatitis (AD), or psoriasis. 
Secondary objectives:  
• 
To assess change in severity of pruritus in subjects with PN, AD, or 
psoriasis using the worst-itch numeric rating scale (WI-NRS).  
• 
To assess change in severity and extent of PN using the Investigator’s 
Global Assessment of PN Stage (IGA PN-S), for those subjects with PN. 
• 
To assess whether serlopitant produces physical dependence.  
Study Design: 
Study MTI-107 is a multicenter, open-label study to assess the long-term safety of 
serlopitant in adults with pruritus associated with PN, AD, or psoriasis. Eligible 
subjects who have completed selected studies of serlopitant may be given the 
opportunity, at the investigator’s discretion, to consent to and participate in this 
open-label study, regardless of their treatment allocation in prior studies. If deemed 
necessary by Menlo Therapeutics to meet enrollment objectives, eligible subjects 
who have not participated in a prior serlopitant study may also be enrolled in study 
MTI-107. 
The study will consist of two periods, for a total study period of approximately 
56 weeks: 
• 
Treatment period: 52 weeks 
• 
Post-drug observation period: 4 weeks 
During the treatment period, subjects will take one serlopitant 5 mg tablet once daily 
orally.  
Standard therapy for the concurrent skin lesions and pruritus may be employed 
during this study.  
After completion of the 52-week treatment period, all subjects will enter a 4-week 
post-drug observation period. Subjects who discontinue treatment early will have a 
post-drug observation visit 4 weeks after their last dose of serlopitant.  
Safety Review: 
An internal safety monitoring team consisting of representatives from Menlo 
Therapeutics Inc. and its designees will monitor safety data on a regular basis 
throughout the study. 
Planned Sample Size: 
Approximately 400 subjects  
Study Population: 
The study will enroll adults with pruritus due to PN, AD, or psoriasis. 
Inclusion Criteria (Subjects must meet the following criteria to be enrolled into the 
study):  
1. Male or female, age 18 years or older at consent. 
2. Subject reports pruritus in the 24-hour period prior to enrollment and: 
a. 
Has completed a prior applicable clinical study of serlopitant 
without a serious adverse event (SAE) that was assessed as likely 
related to the study drug  
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OR  
b. Has not participated in a prior clinical study of serlopitant and has 
a clinical diagnosis of PN, AD, or psoriasis, and Sponsor has 
approved enrollment. 
3. All female subjects who are of childbearing potential must be willing to 
practice highly effective contraception (i.e., pregnancy prevention method 
with a failure rate of <1% per year) from the time of the Baseline visit until 
2 weeks after last dose of study drug. 
4. Willing and able (has adequate cognitive ability, in the investigator’s 
opinion) to comply with study visits and study related requirements 
including providing written informed consent. 
 
Exclusion Criteria (Subjects who meet any of the following criteria are not eligible 
for participation in the study): 
1. Presence of malignancy within 5 years prior to enrollment (exception for 
non-melanoma cutaneous malignancies). 
2. Presence of a psychiatric diagnosis (such as major depressive disorder, 
bipolar disorder, schizophrenia, psychotic disorder, intellectual disability, 
severe alcohol abuse disorder) meeting Diagnostic and Statistical Manual 
of Mental Disorders, Fifth Edition criteria in past 3 years, history of 
suicidal ideation within the past 3 years or any history of suicide attempt.  
3. Presence of any medical condition or disability, that, in the investigator’s 
opinion, could interfere with the assessment of safety in this study or 
compromise the safety of the subject.  
4. Treatment with any investigational therapy within 4 weeks or 5-half-lives 
prior to enrollment (whichever is longer) or expected participation in 
another clinical study involving an investigational product or device during 
the subject’s participation in MTI-107. 
5. Treatment with other neurokinin-1 receptor (NK1-R) antagonists (e.g., 
aprepitant, fosaprepitant, rolapitant) within 4 weeks prior to enrollment. 
6. Treatment with strong cytochrome P450 3A4 inhibitors within 4 weeks 
prior to enrollment. 
7. Currently pregnant or breastfeeding or planning to become pregnant during 
the study. 
Study Drug: 
Serlopitant 5 mg tablets 
Dosage:  
Serlopitant: 5 mg once daily orally for 52 weeks  
Safety Endpoints: 
• 
Incidence of treatment-emergent adverse events (TEAEs) and SAEs 
• 
Changes from baseline in clinical laboratory parameters following study 
drug exposure 
• 
Changes from baseline in vital sign and electrocardiogram (ECG) 
parameters following study drug exposure 
• 
Assessment of physical dependence following chronic study drug exposure, 
in the monitored 4-week post-drug discontinuation period  
Efficacy Endpoints: 
• 
Changes from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52  
• 
Changes from baseline in Patient-Reported Outcomes Measurement 
Information System Itch Questionnaire (PROMIS-PIQ) score for Itch 
(General, Scratching Behavior, Mood and Sleep, Activity and Clothing) to 
Weeks 20, 36, and 52 
• 
Changes from baseline in Dermatology Life Quality Index (DLQI) 
(symptoms and feelings, daily activities, leisure, work or school 
performance, personal relationships, and treatment) to Weeks 20, 36 and 52 
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• 
Changes from baseline in IGA PN-S to Weeks 4, 8, 20, 28, 36, 44, and 52 
Statistical Methods: 
All subjects who receive at least 1 confirmed dose of study drug and have at least 1 
post-baseline safety assessment will be included in the safety population. All 
analyses will be performed using the safety population. 
Data will be summarized with descriptive statistics by visit. For continuous 
variables, the following information will be presented: n, mean, standard deviation, 
median, minimum and maximum. For categorical variables, counts and percentages 
will be used. 
All adverse events (AEs) will be classified by system organ class and preferred term 
using the Medical Dictionary for Regulatory Activities (MedDRA). TEAEs will be 
tabulated in a manner which provides information about the incidence of TEAEs for 
the entire treatment period as well as by specified time periods in order to 
understand the evolution of TEAEs over time. Additionally, the pre-specified 
TEAEs and SAEs that may be associated with physical dependence will be 
summarized separately. An overview of AEs, which includes subject incidence of 
TEAEs, treatment-related TEAEs, TEAEs by severity, SAEs, deaths, and AEs 
leading to discontinuation, will be presented.  
Summary statistics for actual safety laboratory values and for changes from baseline 
will be tabulated by scheduled visit. Subjects with clinical laboratory values outside 
of the normal reference range at any post-baseline assessment will be summarized. 
Shifts from baseline laboratory values will be tabulated. A listing of all out-of-range 
laboratory test results, including assessment of clinical significance will also be 
provided. 
The observed vital sign data and change from baseline will be summarized with 
descriptive statistics and presented in a listing. 
The overall ECG assessment (abnormal or normal) and parameters will be 
summarized along with a summary of how many subjects developed a post-
treatment abnormal result and will be presented in a listing.  
Physical exam findings will be recorded by the sites within medical history or AEs 
and otherwise not summarized, with the exception of weight, and change from 
baseline in weight. 
The WI-NRS, PROMIS-PIQ, DLQI, and IGA PN-S, will be summarized with 
descriptive statistics by visit. 
Study Sites: 
Approximately 120 study sites 
Expected Duration of 
Subject’s 
Participation 
Approximately 56 weeks: 52 weeks of treatment, and a post-drug observation period 
of 4 weeks. 
 
This study will be conducted in accordance with the Guidelines of Good Clinical Practice. 
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TABLE OF CONTENTS 
SIGNATURE PAGE FOR INVESTIGATOR(S) .....................................................................2 
SPONSOR PROTOCOL APPROVAL SIGNATURE(S) .........................................................3 
PROTOCOL SYNOPSIS ..........................................................................................................4 
TABLE OF CONTENTS ...........................................................................................................7 
LIST OF APPENDICES ..........................................................................................................10 
LIST OF TABLES ...................................................................................................................10 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..........................................11 
1 
INTRODUCTION .................................................................................................12 
1.1 
Pruritus .............................................................................................................12 
1.1.1 
Role of Substance P and the Neurokinin-1 Receptor in Pruritus .........12 
1.2 
Serlopitant ........................................................................................................13 
1.2.1 
Serlopitant Background and Nonclinical Summary ............................13 
1.2.2 
Serlopitant Clinical Summary ..............................................................14 
1.2.3 
Serlopitant in Pruritus-Related Studies ................................................14 
2 
STUDY OBJECTIVES ..........................................................................................16 
3 
STUDY DESIGN...................................................................................................16 
3.1 
Overall Study Design .......................................................................................16 
3.2 
Rationale for Study Design and Dose Selection ..............................................17 
3.3 
Study Endpoints ...............................................................................................17 
3.3.1 
Safety Endpoints ..................................................................................17 
3.3.2 
Efficacy Endpoints ...............................................................................17 
3.4 
Safety Review ..................................................................................................18 
3.4.1 
Safety Monitoring Team ......................................................................18 
4 
SELECTION OF STUDY POPULATION ...........................................................18 
4.1 
Study Population ..............................................................................................18 
4.2 
Inclusion Criteria .............................................................................................18 
4.3 
Exclusion Criteria ............................................................................................19 
5 
STUDY DRUG ......................................................................................................19 
5.1 
Study Drug Supply, Route of Administration, and Storage.............................19 
5.2 
Labeling and Study Drug Accountability ........................................................20 
5.3 
Dosing Regimen...............................................................................................20 
5.4 
Dose Modification ...........................................................................................20 
5.5 
Missed or Delayed Doses.................................................................................20 
5.6 
Study Drug Discontinuation ............................................................................20 
5.7 
Concomitant and Excluded Therapies .............................................................21 
5.7.1 
Excluded Therapies ..............................................................................21 
5.8 
Assignment to Treatment .................................................................................21 
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5.9 
Treatment Compliance .....................................................................................22 
6 
STUDY SCHEDULE AND ASSESSMENTS ......................................................22 
6.1 
Efficacy Parameters .........................................................................................22 
6.1.1 
Itch Numeric Rating Scale ...................................................................22 
6.1.2 
Investigator’s Global Assessment of PN Stage ...................................22 
6.1.3 
Patient-Reported Outcomes Measurement Information System Itch 
Questionnaire .......................................................................................22 
6.1.4 
Dermatology Life Quality Index ..........................................................22 
6.1.5 
Photographs..........................................................................................23 
6.2 
Safety Parameters.............................................................................................23 
6.2.1 
Vital Signs ............................................................................................23 
6.2.2 
Physical Examination...........................................................................23 
6.2.3 
Clinical Laboratory Assessments .........................................................23 
6.2.4 
Electrocardiogram ................................................................................24 
6.2.5 
Assessment of Potential for Physical Dependence ..............................24 
6.3 
Subject Flow Diagram .....................................................................................24 
6.4 
Study Visits ......................................................................................................24 
6.4.1 
Baseline Visit .......................................................................................24 
6.4.2 
Week 4 Visit ........................................................................................26 
6.4.3 
Week 8 Visit ........................................................................................26 
6.4.4 
Week 12 Visit ......................................................................................27 
6.4.5 
Week 20 Visit ......................................................................................27 
6.4.6 
Week 28 Visit ......................................................................................28 
6.4.7 
Week 36 Visit ......................................................................................29 
6.4.8 
Week 44 Visit ......................................................................................30 
6.4.9 
Week 52 Visit ......................................................................................30 
6.4.10 
Early Treatment Discontinuation Visit/Post-Drug Observation ..........31 
6.4.11 
Early Termination ................................................................................32 
7 
ASSESSMENT OF SAFETY ................................................................................32 
7.1 
Definitions........................................................................................................32 
7.1.1 
Adverse Event ......................................................................................32 
7.1.2 
Serious Adverse Event .........................................................................32 
7.1.3 
Abnormal Physical Exam, Laboratory, Vital Sign, and 
Electrocardiogram Findings .................................................................33 
7.1.4 
Deaths ..................................................................................................34 
7.1.5 
Pregnancies and Contraception Requirements for Females .................34 
7.1.6 
Worsening of Pruritus or Underlying Pruritic Skin Disease ................35 
7.2 
Methods and Timing for Recording and Reporting Adverse Events ...............35 
7.2.1 
Adverse Event Reporting Period .........................................................35 
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7.2.2 
Eliciting Adverse Events......................................................................35 
7.2.3 
Assessment of Severity ........................................................................36 
7.2.4 
Assessment of Causality ......................................................................36 
7.3 
Follow-up of Adverse Events and Serious Adverse Events ............................37 
7.4 
Reporting Serious Adverse Events to the Sponsor and Institutional Review 
Board (IRB) or Ethics Committee (EC)...........................................................37 
7.5 
Reporting Serious Adverse Events to Regulatory Authorities and Study 
Investigators .....................................................................................................37 
8 
STATISTICAL METHODS ..................................................................................38 
8.1 
Handling of Missing Data and Excluded Therapy Use ...................................38 
8.2 
Analysis Population .........................................................................................38 
8.3 
Subject Disposition ..........................................................................................38 
8.4 
Subject Characteristics .....................................................................................38 
8.5 
Concomitant Medications ................................................................................38 
8.6 
Treatment Compliance and Extent of Exposure ..............................................38 
8.7 
Efficacy Analyses ............................................................................................39 
8.8 
Safety Analyses ................................................................................................39 
8.8.1 
Adverse Events ....................................................................................39 
8.8.2 
Clinical Safety Laboratory Results ......................................................40 
8.8.3 
Vital Signs ............................................................................................40 
8.8.4 
Electrocardiograms ..............................................................................40 
8.8.5 
Physical Exams ....................................................................................40 
9 
ADMINISTRATIVE ASPECTS ...........................................................................40 
9.1 
Changes to the Protocol ...................................................................................40 
9.2 
Study Termination ...........................................................................................41 
9.3 
Monitoring and Auditing Procedures...............................................................41 
9.4 
Transfer of Obligations ....................................................................................41 
9.5 
Informed Consent.............................................................................................41 
9.6 
Communication with the Institutional Review Board or Ethics Committee ...41 
9.7 
Disclosure and Confidentiality ........................................................................42 
9.8 
Records and Electronic Case Report Forms ....................................................42 
9.9 
Good Clinical Practice and Ethical Study Conduct .........................................43 
9.10 
End of Study Notification ................................................................................43 
9.11 
Publication of Results ......................................................................................43 
9.12 
Final Report .....................................................................................................43 
10 
REFERENCES ......................................................................................................44 
 
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LIST OF APPENDICES 
Appendix A  Schedule of Activities and Assessments ..........................................................46 
Appendix B  List of Strong CYP3A4 Inhibitors ...................................................................47 
 
LIST OF TABLES 
Table 1 
Adverse Event Grading ..............................................................................36 
  
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS   
Abbreviation 
Definition 
AD 
Atopic dermatitis  
ADL 
Activities of daily living 
AE 
Adverse event 
ALT 
Alanine aminotransferase  
AMH 
Anti-Mullerian hormone 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Classification 
CYP3A4 
cytochrome-P 3A4  
DLQI 
Dermatology Life Quality Index 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
ETD 
Early Treatment Discontinuation 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
FSH 
Follicle-stimulating hormone 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IGA PN-S 
Investigator’s Global Assessment of Prurigo Nodularis Stage 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System  
LDH 
Lactate dehydrogenase 
LH 
Luteinizing hormone 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NK1-R 
Neurokinin-1 receptor 
NRS 
Numeric rating scale  
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PROMIS-PIQ 
Patient-Reported Outcomes Measurement Information System Itch Questionnaire (PIQ) 
PN 
Prurigo nodularis 
QOL 
Quality of life 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan  
SP 
Substance P 
TEAE 
Treatment-emergent adverse event 
VAS 
Visual Analog Scale 
WI-NRS 
Worst-Itch Numeric Rating Scale 
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1 
INTRODUCTION 
1.1 
Pruritus  
Pruritus, or itch, is defined as an unpleasant sensation that evokes a desire to scratch 
(Ikoma 2006). Itch and pain, although closely related, are distinct sensations: itch elicits a 
scratching response, whereas pain causes a withdrawal response.  
Emerging research in neurobiology has greatly expanded the understanding of pruritus 
signaling. Pruritoceptors (itch-sensory nerve fibers) consist of two distinct classes of nerve 
fibers: histamine-responsive mechanoinsensitive C-fibers, and histamine-unresponsive 
mechanosensitive polymodal C and Aδ fibers that are activated by cowhage (highly pruritic 
spicules from the pods of the cowhage plant Mucuna pruriens) (Schmelz 2015). The second 
class of histamine-unresponsive, cowhage-responsive nerve fibers has been of particular 
interest in pruritus research, as C-fibers that have a strong and sustained response to 
histamine comprise only about 20% of the overall mechanoinsensitive C-fiber population 
(Steinhoff 2006), and a significant proportion of chronic pruritic conditions do not appear to 
involve histamine-mediated pruritus signaling (Ikoma 2006). Substance P (SP) is a prominent 
pruritogen (itch mediator) in this histamine-independent pruritus pathway (Chuquilin 2016).  
Pruritus stimuli in the skin are transmitted via sensory neurons that have their cell bodies in 
the dorsal root ganglia (DRG) and are linked to second-order neurons in the spine 
(Carstens 2016, Luo 2015). Following activation of these DRG sensory neurons, the pruritus 
signal is transmitted to the second-order spinal neurons primarily by SP, gastrin-releasing 
peptide, and glutamate in histamine-independent pruritus, and primarily by glutamate in 
histamine-mediated pruritus (Chuquilin 2016). 
Spinal itch neuron projections ascend via the contralateral spinothalamic tract to the thalamus 
and via the lateral spinoparabrachial tract to the lateral parabrachial nucleus, from which 
point they activate multiple centers in the somatosensory cortex, the premotor cortex, and the 
cingulate cortex – areas involved in the sensory processing and motor response (scratching) 
to the itch signal (Carstens 2016, Chuquilin 2016). 
1.1.1 
Role of Substance P and the Neurokinin-1 Receptor in Pruritus 
Substance P is an undecapeptide that belongs to the tachykinin family of neuropeptides, a 
group that also includes neurokinin A and neurokinin B (Hökfelt 2001). SP has been 
implicated in a number of biological functions, both physiological and pathophysiological, 
including pruritus perception, vomiting reflex, pain perception, and immunomodulatory 
responses (Lotts 2014, Andoh 1998, Steinhoff 2014).  The biological actions of SP are 
mediated by tachykinin receptors, which consist of seven hydrophobic transmembrane 
domains coupled to G-proteins. Three tachykinin receptors have been identified: the 
neurokinin-1 (NK1-R), neurokinin-2, and neurokinin-3 receptors (Harrison 2001). The 
neurokinin-1 receptor, in particular, has been studied in great detail. NK1-R is the primary 
receptor for SP in the human body, and is found on multiple cell types, including central and 
peripheral neurons, keratinocytes, mast cells, and dendritic cells (El-Nour 2006, 
Ständer 2015).  
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NK1-R stimulation has been shown to be an important pathway for pruritus perception 
(Ständer 2015). Inhibition of this pathway results in decreased pruritus and scratching 
reflexes in animal models (Akiyama 2015). Preceding the development of serlopitant for 
pruritus-related conditions, a commercially available NK1-R antagonist (Emend USPI) has 
been used as a therapy to decrease pruritus in patients with chronic pruritus due to etiologies 
such as cutaneous T-cell lymphoma (Duval 2009, Torres 2012, Booken 2011) and erlotinib-
induced pruritus (Santini 2012, Gerber 2010). Additionally, in a study of 20 patients with 
chronic pruritus of various etiologies treated with aprepitant, 16/20 patients (80%) 
experienced a considerable reduction of itch intensity (Ständer 2010).  
1.2 
Serlopitant 
1.2.1 
Serlopitant Background and Nonclinical Summary 
Serlopitant is a small molecule, highly selective NK1-R antagonist that is administered orally 
and metabolized by cytochrome-P 3A4 (CYP3A4), with a plasma half-life of 45-86 hours. It 
binds with high affinity to the human NK1-R with a dissociation constant (Kd) of 46 pM; 
displacing SP binding with a half-maximal inhibition concentration (IC50) of 61 pM. 
Serlopitant is a potent functional antagonist of SP-induced inositol phosphate generation. 
Serlopitant has been extensively studied in animal toxicology studies, including chronic 
toxicology and carcinogenicity studies. In non-clinical chronic toxicology studies in rats, 
mice and dogs, treatment related findings of potential clinical significance included increased 
salivation, decreased body weight gain and food consumption, slight changes in hematology 
and serum biochemistry parameters, mild increases in liver weight and mild 
histomorphologic changes. The histomorphologic changes were seen only in rats (not in dogs 
or mice) and included: very slight ovarian interstitial cell hypertrophy, mammary gland and 
uterine atrophy; decreased corpora lutea; increased histiocytes in lung and mesenteric lymph 
nodes; slight skeletal and cardiac muscle degeneration; slight increased hematopoiesis in 
bone marrow; and slight to moderate vacuolation in kidney tubules. These nonclinical 
findings occurred at systemic exposures exceeding those anticipated to provide efficacy of 
serlopitant for pruritus indications in humans (1 to 5 mg tablet daily). No cardiac lesions have 
been observed in dog toxicity studies up to 9 months in duration nor in a 3-month mouse 
range-finding study and 2-year mouse carcinogenicity study at exposure higher than the 
lowest level which caused cardiotoxicity in rats. The no observed adverse effect level 
(NOAEL) in rats for histomorphological changes in the reproductive tract, mammary gland 
and bone marrow provides a 2.5-fold margin for the maximum-targeted exposure (5 mg 
tablet daily). The rat NOAEL for histomorphological changes in muscle and kidney provides 
a 5-fold margin for the maximum-targeted exposure (5 mg tablet daily).  
In summary, the nonclinical toxicity noted with serlopitant provides no contraindications to 
the continuation of clinical trials via the oral route. Findings in the developmental toxicity 
studies support inclusion of women of childbearing potential in clinical trials in accordance 
with the study protocol and local regulatory guidances.  
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1.2.2 
Serlopitant Clinical Summary 
In humans, serlopitant has been administered to over 1000 individuals. Single doses up to 
400 mg have been well tolerated in young adult males and single doses up to 25 mg have 
been well tolerated in the elderly. Multiple doses of up to 50 mg a day for 4 weeks have been 
well tolerated in healthy young males, and a single (loading) dose of 15 mg followed by daily 
doses of 5 mg for 2 weeks have been well tolerated in elderly males and females. Forty-one 
(41) subjects received 4 mg liquid filled capsule (LFC) daily (bioequivalent to 5 mg tablets) 
for 1 year. Plasma concentrations of serlopitant appear to increase in a dose-proportional 
fashion in both young males and elderly subjects (males and females). Peak plasma 
concentrations after a single oral dose occurred at ~2 to 4 hours in both young and elderly 
subjects. A single loading dose of up to 15 mg followed by 6 to 8 weeks of up to 5 mg daily 
doses has been well tolerated in adults with chronic pruritus and prurigo nodularis (PN). 
Pharmacokinetic data demonstrate good plasma exposures with oral dosing, linear dose-
dependent increases in plasma concentration and systemic exposure, a plasma t1/2 
appropriate for once daily dosing, and mild effects of concomitant food ingestion. Central 
nervous system (CNS) positron emission tomography (PET) studies have demonstrated good 
CNS penetrance and > 90% NK1 receptor occupancy (RO) at plasma exposures anticipated 
to be safe and well tolerated. Three long-lived active hydroxylated metabolites are observed 
in humans: M1/M1a 
, M2/M2a 
, and M3 
. 
These metabolites were present at lower concentrations and were 2- to 9-fold less potent in 
vivo than the parent compound. The integrated pharmacokinetic/pharmacodynamic (PK/PD) 
analysis concluded that these metabolites are unlikely to contribute significantly to 
occupancy of the CNS NK1-R in humans. 
1.2.3 
Serlopitant in Pruritus-Related Studies 
Serlopitant has been evaluated in two completed Phase 2 studies of subjects with chronic 
pruritus (TCP-101 and TCP-102).  
TCP-101 
TCP-101 was a double-blind, placebo-controlled, multi-center study that compared 
serlopitant 0.25 mg, 1 mg, or 5 mg vs. placebo for the treatment of chronic pruritus. A total 
of 257 adult subjects 18-65 years of age with chronic pruritus were randomized to receive 
one of the four dose groups in a 1:1:1:1 randomization. Subjects received a loading dose of 
3 tablets on Day 1 and thereafter received 1 tablet per day for 6 weeks. The primary efficacy 
endpoint was itch severity as measured on a Visual Analog Scale (VAS), summarized as a 
percentage change from baseline. 
Mean percent decreases from Baseline in VAS score were larger in the active-treatment 
groups versus placebo at every scheduled post-baseline study visit. Overall, the results were 
the most profound for the serlopitant 1 mg and 5 mg groups. For the percent change from 
Baseline in VAS pruritus scores (the primary efficacy variable), the Week 6 pairwise least 
squares mean difference compared to placebo was 5.8 mm, 13.2 mm, and 14.2 mm for 
serlopitant 0.25 mg, 1 mg, and 5 mg, respectively.   
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The frequency of treatment-emergent adverse events (TEAEs) and study drug related adverse 
events (AEs) was higher in the serlopitant 1 mg and 5 mg groups compared to the serlopitant 
0.25 mg group, and the frequency in all three treatment groups were higher than in the 
placebo group. The frequency of AEs leading to study drug discontinuation was comparable 
in the serlopitant 5 mg and placebo group and higher than in the serlopitant 0.25 mg and 
1 mg groups. There was one serious adverse event (SAE) reported in the serlopitant 1 mg 
group (spontaneous abortion, considered not related). There were no deaths. The most 
common AEs in the serlopitant groups were diarrhea (6.2%, 1 mg group), upper respiratory 
tract infection (4.7%, 0.25 mg group), somnolence (4.7%, 5 mg group), nasopharyngitis 
(4.6%, 1 mg group), headache (4.7%, 5 mg group), urinary tract infection (3.1%, 5 mg 
group), dry mouth (3.1%, 1 mg group), nausea (3.1%, 1 mg group), arthralgia (3.1%, 0.25 
mg group), musculoskeletal pain (3.1%, 1 mg group) and pruritus (3.1%, 1 mg group). The 
most common AEs in the placebo group were headache (6.3%), nasopharyngitis (3.2%), 
upper respiratory tract infection (3.2%), urinary tract infection (3.2%) and asthma (3.2%).  
TCP-102 
TCP-102 was a randomized, double-blind, placebo-controlled multi-center study that 
evaluated serlopitant 5 mg vs. placebo for the treatment of PN A total of 128 adult subjects 
18-80 years of age with PN were randomized to receive serlopitant or placebo in a 1:1 
randomization. Subjects received a loading dose of 3 tablets on Day 1 followed by 1 tablet 
per day for 8 weeks. The primary efficacy endpoint was the average VAS score as recorded 
at the study visits. Results at Week 4 and Week 8 were the primary timepoints. 
Serlopitant 5 mg was superior to placebo for the reduction of pruritus as measured by change 
in average VAS from baseline. For the primary endpoint, change from baseline at Week 4 
and Week 8 by repeated measures analysis, the decrease from baseline was significantly 
greater in the serlopitant group than the placebo group, with a mean difference (serlopitant 
minus placebo) of -1.0 at Week 4 and -1.7 at Week 8. The mean difference at Week 2 was 
also significant, -0.9. In a post-hoc analysis of the percentage of subjects who were 4-point 
responders on average VAS at Week 8, 25.0% of placebo subjects and 54.4% of serlopitant 
subjects were 4-point responders. 
TEAEs were reported for 71.9% of serlopitant-treated subjects and 61.9% of placebo-treated 
subjects. The most frequently reported TEAEs in the serlopitant group were nasopharyngitis 
(17.2% serlopitant, 3.2% placebo), diarrhea (10.9% serlopitant, 4.8% placebo), and fatigue 
(9.4% serlopitant, 6.3% placebo). Treatment-related TEAEs were reported for 48.4% of 
serlopitant-treated subjects and 34.9% of placebo-treated subjects. The most frequently 
reported treatment-related TEAEs in the serlopitant group were fatigue (7.8%) and diarrhea, 
peripheral edema, dizziness, and headache (each 6.3%). Most TEAEs were mild or moderate; 
severe TEAEs were reported for 9.4% of serlopitant-treated subjects and 4.8% of placebo-
treated subjects. There were no deaths during the study. Five subjects (3 serlopitant, 
2 placebo) had SAEs. The SAEs were actinic elastosis, depression, dizziness, and vertigo in 
the serlopitant group; and bradycardia, syncope, respiratory failure, and neurodermatitis in 
the placebo group. Nine subjects (3 serlopitant, 6 placebo) discontinued due to TEAEs. 
No clinically relevant changes were observed in chemistry, hematology, vital signs, or 
electrocardiogram (ECG) results. 
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The results of the Phase 2 studies in PN and chronic pruritus, together with the extensive 
safety experience with serlopitant to date and the scientific rationale for NK1-R inhibition in 
the treatment of pruritus, serve to support further evaluation of serlopitant for the treatment 
of pruritus in subjects with PN (in concurrent Phase 3 studies MTI-105 and MTI-106), atopic 
dermatitis (AD) (in ongoing Phase 2 study MTI-103), and psoriasis (in ongoing Phase 2 
study MTI-109).   
Please refer to the Investigator’s Brochure for further information regarding serlopitant. 
2 
STUDY OBJECTIVES  
The primary objective of this study is to assess the long-term safety of serlopitant in adults 
with pruritus associated with PN, AD, or psoriasis. 
The secondary objectives of this study are to assess the change in severity of pruritus in 
subjects with PN, AD, or psoriasis using the worst-itch numeric rating scale (WI-NRS); to 
assess the change in severity and extent of PN using the Investigator’s Global Assessment of 
PN Stage (IGA PN-S), for those subjects with PN; and to assess whether serlopitant produces 
physical dependence. 
3 
STUDY DESIGN 
3.1 
Overall Study Design 
This is a multicenter, open-label study to assess the long-term safety of serlopitant in adults 
with pruritus associated with PN, AD, or psoriasis. Eligible subjects who have completed 
selected studies of serlopitant may be given the opportunity, at the investigator’s discretion, 
to consent to and participate in this open-label study, regardless of their treatment allocation 
in prior studies. If deemed necessary by Menlo Therapeutics to meet enrollment objectives, 
eligible subjects who have not participated in a prior serlopitant study may also be enrolled in 
study MTI-107. Approximately 120 study sites may enroll subjects in this long-term safety 
study. 
This study will consist of two periods, for a total study period of approximately 56 weeks: 
• Treatment period: 52 weeks 
• Post-drug observation period: 4 weeks 
 
During the treatment period, subjects will take one serlopitant 5 mg tablet once daily orally 
(Section 5.3).  
Standard therapy for the concurrent skin lesions and pruritus may be employed during this 
study (Section 5.7.1).  
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The WI-NRS during a 24-hour recall period will be assessed by the subject at each study 
visit. 
For those subjects with PN, the severity and extent of PN will be assessed at selected visits, 
using the IGA-PN-S, and photographs of representative areas with PN will be taken at 
selected visits at a subset of sites. 
The Patient-Reported Outcomes Measurement Information System Itch Questionnaire 
(PROMIS-PIQ) and the Dermatology Life Quality Index (DLQI) will be administered at 
selected visits. 
After completion of the 52-week treatment period, all subjects will enter a 4-week post-drug 
observation period. Subjects who discontinue treatment early will have a post-drug 
observation visit 4 weeks after their last dose of serlopitant. During this monitored 
discontinuation period, solicited safety evaluations will assess the potential for serlopitant to 
produce physical dependence. 
3.2 
Rationale for Study Design and Dose Selection 
The current MTI-107 study is designed to confirm the long-term safety of serlopitant for the 
treatment of pruritus in patients with PN, AD, and psoriasis. The 5 mg dose of serlopitant 
was selected for this study based on the favorable efficacy, safety, and tolerability profile of 
serlopitant at this dose level in completed studies.  
3.3 
Study Endpoints 
3.3.1 
Safety Endpoints 
The safety endpoints are as follows: 
• Incidence of TEAEs and SAEs 
• Changes from baseline in clinical laboratory parameters following study drug exposure 
• Changes from baseline in vital sign and ECG parameters following study drug exposure 
• Assessment of physical dependence following chronic study drug exposure, in the 
4-week post-drug discontinuation period.  
 
3.3.2 
Efficacy Endpoints 
The efficacy endpoints are as follows: 
• Changes from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52  
• Changes from baseline in PROMIS-PIQ score for Itch (General, Scratching Behavior, 
Mood and Sleep, Activity and Clothing) to Weeks 20, 36, and 52 
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•
Changes from baseline in DLQI (symptoms and feelings, daily activities, leisure, work or
school performance, personal relationships, and treatment) to Weeks 20, 36 and 52
•
Changes from baseline in IGA PN-S to Weeks 4, 8, 20, 28, 36, 44, and 52
3.4 
Safety Review 
3.4.1 
Safety Monitoring Team 
An internal safety monitoring team consisting of representatives from Menlo Therapeutics 
Inc. and its designees will monitor safety data on a regular basis throughout the study. 
4 
SELECTION OF STUDY POPULATION 
4.1 
Study Population 
Approximately 400 adult subjects with pruritus due to PN, AD, or psoriasis will be enrolled 
in this study. 
4.2 
Inclusion Criteria 
Subjects must meet the following criteria to be enrolled into the study: 
1. Male or female, age 18 years or older at consent.
2. Subject reports pruritus in the 24-hour period prior to enrollment and:
a.
Has completed a prior applicable clinical study of serlopitant without an SAE that
was assessed as likely related to the study drug
OR
b. Has not participated in a prior clinical study of serlopitant and has a clinical diagnosis
of PN, AD, or psoriasis, and Sponsor has approved enrollment.
3. All female subjects who are of childbearing potential must be willing to practice highly
effective contraception (i.e., pregnancy prevention method with a failure rate of <1% per
year, refer to section 7.1.5 for acceptable methods of contraception) from the time of the
Baseline visit until 2 weeks after last dose of study drug.
4. Willing and able (has adequate cognitive ability, in the investigator’s opinion) to comply
with study visits and study related requirements including providing written informed
consent.
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4.3 
Exclusion Criteria 
Subjects who meet any of the following criteria are not eligible for participation in the study: 
1. Presence of malignancy within 5 years prior to enrollment (exception for non-melanoma 
cutaneous malignancies). 
2. Presence of a psychiatric diagnosis (such as major depressive disorder, bipolar disorder, 
schizophrenia, psychotic disorder, intellectual disability, severe alcohol abuse disorder) 
meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria in 
past 3 years, history of suicidal ideation within the past 3 years or any history of suicide 
attempt.  
3. Presence of any medical condition or disability, that, in the investigator’s opinion, could 
interfere with the assessment of safety in this study or compromise the safety of the 
subject.  
4. Treatment with any investigational therapy within 4 weeks or 5-half-lives prior to 
enrollment (whichever is longer) or expected participation in another clinical study 
involving an investigational product or device during the subject’s participation in MTI-
107. 
5. Treatment with other neurokinin-1 receptor (NK1-R) antagonists (e.g., aprepitant, 
fosaprepitant, rolapitant) within 4 weeks prior to enrollment. 
6. Treatment with strong cytochrome P450 3A4 inhibitors within 4 weeks prior to 
enrollment (Appendix B). 
7. Currently pregnant or breastfeeding or planning to become pregnant during the study. 
 
5 
STUDY DRUG 
5.1 
Study Drug Supply, Route of Administration, and Storage 
The study drug in this study is serlopitant 5 mg in a film-coated tablet formulation for oral 
administration. The serlopitant tablets contain microcrystalline cellulose, mannitol, 
croscarmellose sodium, silicon dioxide, sodium lauryl sulfate, and magnesium stearate, and 
are film coated with Opadry® Brown.  
The study drug will be provided in bottles that can be stored at room temperature (59-86°F, 
15-30°C). 
Each bottle will each contain 18 serlopitant tablets.  
Additional details regarding study drug supplies can be found in the Pharmacy Manual. 
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5.2 
Labeling and Study Drug Accountability 
The study drug will be appropriately packaged and labeled in bottles with 18 tablets per 
bottle. The study drug supplied for this study is not to be used for any purpose other than this 
study, and study drug accountability must be maintained for all bottles distributed to the 
investigative site. 
Additional details regarding study drug labeling and accountability can be found in the 
Pharmacy Manual. 
5.3 
Dosing Regimen 
During the treatment period, subjects will take one serlopitant 5 mg tablet once daily orally.  
Subjects will be instructed to take all doses from Baseline Visit (Study Day 1) until the Week 
52 Visit, once a day and not within 2 hours before or after a meal. 
Should the study drug be withheld (without intent to discontinue study drug, Section 5.6), the 
drug may be resumed at the discretion of the investigator, at the same dosing regimen.  
5.4 
Dose Modification 
No dose modification of study drug will be allowed during this study.  
5.5 
Missed or Delayed Doses 
Each dose of study drug after the first dose must be administered once daily, and not within 
2 hours before or after a meal. If a dose is missed, that dose will be considered and 
documented as a missed dose.  Dosing should resume as directed the next day. 
5.6 
Study Drug Discontinuation 
Subjects should be discontinued from study drug in the following situations: 
• Any medical condition that may jeopardize the subject’s safety if study drug is continued, 
in the investigator’s and/or Sponsor’s opinion 
• Baseline serum creatinine, total bilirubin, alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) > 2.5 times the upper limit of normal (ULN) (exception may be 
made for retesting within 28 days of enrollment as approved by the Medical Monitor) 
• A female subject becomes pregnant 
• The subject decides to discontinue study drug, or withdraws consent from the study 
• The subject reports use of a strong CYP3A4 inhibitor (as listed in Appendix B) within 4 
weeks of the study visit at which it was reported, initiates any investigational medication, 
or other NK1-R antagonist (exception may be made for use of approved NK1-R 
antagonist for less than 5 continuous days) 
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• Discontinuation is deemed to be in the best interest of the subject, in the investigator’s 
and/or Sponsor’s opinion 
 
The Sponsor or designee should be contacted within 24 hours of investigator’s awareness of 
any study drug discontinuation due to an AE or pregnancy. Investigators should make every 
effort to contact the Sponsor or designee before discontinuing study drug, if possible. 
Subjects who discontinue study drug prior to completing the treatment period will enter a 4-
week follow-up period following the last dose of study drug (Section 6.4.10). Every effort 
should be made for subjects to complete this follow-up visit after a subject has discontinued 
from study drug.  
5.7 
Concomitant and Excluded Therapies 
Concomitant therapies include any therapies (including over-the-counter medications) used 
by a subject from initiation of study drug through the follow-up period. A record of all 
medications used will be maintained for each subject throughout the study. Reported 
information will include a description of the type of drug, treatment period, dosing regimen, 
the route of administration, and drug indication. The use of any concomitant medication must 
relate to the subject’s medical history or to an AE, except for vitamins/nutritional 
supplements and routine preventative immunizations.  
5.7.1 
Excluded Therapies 
The following therapies and activities are excluded from the Baseline visit through the 
follow-up period: 
• NK1-R antagonists (other than study drug, exception may be made for use of approved 
NK1-R antagonist for less than 5 continuous days) 
• Strong CYP3A4 inhibitors (See Appendix B; exceptions may be made for use within 4 
weeks of the study visit at which it was reported) 
• Any investigational drug therapy other than serlopitant 
 
Use of any excluded therapies should be reported as soon as possible, and will be recorded as 
protocol deviations for subjects who receive them. Subjects may be discontinued from the 
study drug (Section 5.6). 
5.8 
Assignment to Treatment  
Eligible subjects will receive serlopitant 5 mg tablets. 
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5.9 
Treatment Compliance 
Records of study drug used, dosages administered, and intervals between visits will be kept 
during the study. Subjects will be asked to return all partially used and empty bottles to the 
study site at each visit. The site staff will count and record the number of remaining tablets in 
each returned bottle. Missed doses will be recorded as reported by the subject. A subject who 
has deviated significantly from the once-daily dosing regimen will be counseled. 
6 
STUDY SCHEDULE AND ASSESSMENTS  
6.1 
Efficacy Parameters 
6.1.1 
Itch Numeric Rating Scale 
The Itch NRS is a validated, self-reported instrument for measurement of itch intensity. WI-
NRS scores will be captured as per Appendix A. Subjects are asked to rate the intensity of 
their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher 
scores indicate greater itch intensity. In this study, WI-NRS during a 24-hour recall period 
prior to the specified visit will be captured.  
6.1.2 
Investigator’s Global Assessment of PN Stage 
The IGA PN-S is an instrument used to assess the overall number and thickness of PN 
lesions at a given time point, as determined by the investigator. It consists of a 5-point scale 
ranging from 0 (clear) to 4 (severe). The IGA PN-S uses clinical characteristics including the 
number of nodules and their thickness, as guidelines for the overall severity assessment. 
IGA PN-S scores will be captured as per Appendix A. Each assessment during the study 
must be done by the principal investigator (PI) or designee. Every effort should be made to 
ensure that all assessments for a given subject are done by the same individual throughout the 
study. However, a change in assessor for a given subject, though not ideal, will not be 
considered a protocol deviation. 
6.1.3 
Patient-Reported Outcomes Measurement Information System Itch 
Questionnaire  
PROMIS-PIQ is an itch-specific instrument that measures quality of life impairment related 
to itch in the previous week. The PROMIS-PIQ includes 4 domains (General, Scratching 
Behavior, Mood and Sleep, and Activity and Clothing). Subjects will complete the PROMIS-
PIQ short forms as per Appendix A.    
6.1.4 
Dermatology Life Quality Index  
DLQI is a dermatology specific quality of life instrument designed to assess the impact of the 
skin disease on a subject’s quality of life over the prior week. It is a ten-item questionnaire 
that assesses overall quality of life (QOL) and six aspects that may affect QOL (symptoms 
and feelings, daily activities, leisure, work or school performance, personal relationships, and 
treatment). The DLQI questionnaire will be collected as per Appendix A. 
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6.1.5 
Photographs 
At selected investigative sites, optional photographs of representative areas with PN 
involvement will be taken at multiple time points, as per Appendix A. These areas may 
include the extensor surfaces of both arms and both legs (overview of both legs, detail of 
lower legs), and the abdomen and back. The central photography vendor will provide 
photographic equipment to the sites for use during the study. Detailed instructions will be 
provided in a Photography Manual. 
6.2 
Safety Parameters 
Safety assessments will consist of monitoring and recording protocol-defined AEs and SAEs; 
vital signs; physical examinations; clinical laboratory assessments; ECGs; and other 
protocol-specified tests that are deemed critical to the safety evaluation of the study drug. 
6.2.1 
Vital Signs 
Vital signs will include measurements of heart rate, blood pressure, respiration rate, and 
temperature after the subject has been calmly resting (seated or supine) for a minimum of 
5 minutes. Vital signs will be assessed as per Appendix A and at unscheduled study visits 
when clinically indicated. When possible, assessment of vital signs should precede blood 
draw.  
6.2.2 
Physical Examination 
Physical examinations will be performed as per Appendix A and at unscheduled study visits 
when clinically indicated. A complete physical examination will be performed at the 
Baseline visit, while subsequent examinations will be abbreviated and targeted to changes in 
disease activity and/or subjects’ symptoms. The subjects’ height and weight will be measured 
as per Appendix A. 
6.2.3 
Clinical Laboratory Assessments 
Samples for clinical laboratory assessments will be collected as per Appendix A and at 
unscheduled study visits when clinically indicated, and analyzed at a central laboratory 
unless otherwise specified. When possible, blood draws should follow ECGs and vital sign 
measurements if they occur on the same visit.  
Detailed instructions regarding sample collection, preparation, and shipment can be found in 
the laboratory manual. Laboratory assessments will include the following: 
•
Hematology: hematocrit, hemoglobin, red blood cell count, red blood cell indices,
platelets, white blood cell count, white blood cell differential (neutrophils, lymphocytes,
monocytes, basophils, eosinophils)
•
Chemistry: sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen,
creatinine, calcium, phosphorus, magnesium, albumin, uric acid, total protein, alanine
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aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total 
bilirubin, lactate dehydrogenase (LDH), lipid panel 
•
Pregnancy testing: all females of childbearing potential will have a local urine pregnancy
test performed. Positive or equivocal urine pregnancy test results will be confirmed by a
serum pregnancy test analyzed at a central laboratory
•
Reproductive endocrinology (for all female subjects under 55 years of age at consent):
serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol,
progesterone, anti-Mullerian hormone (AMH)
6.2.4 
Electrocardiogram 
A standard 12-lead ECG will be performed after the subject has been calmly resting in a 
supine position for a minimum of 5 minutes before obtaining the ECG. When possible, ECGs 
should precede measurement of vital signs and blood draw for clinical laboratory tests. ECGs 
will be performed as per Appendix A and at unscheduled study visits when clinically 
indicated. ECGs will be reviewed and reported by a central ECG vendor. The ECG machine 
and detailed instructions will be provided by the ECG vendor. 
6.2.5 
Assessment of Potential for Physical Dependence 
NK1-R antagonist dependence has not previously been described and therefore a drug class-
specific, reliable and sensitive instrument for the assessment of withdrawal symptoms has not 
been developed. A surrogate assessment tool, such as those developed for opioid or 
benzodiazepine dependence, is not available. 
In the statistical analysis plan (SAP), the Sponsor will specify a targeted medical event list 
(TEAEs) that may be associated with physical dependence, and evaluate reports of these 
events in the monitored 4-week post-drug discontinuation period.   
6.3 
Subject Flow Diagram 
The visit schedule and assessments are summarized in Appendix A. 
6.4 
Study Visits 
The following sections describe the procedures and assessments to be performed at each 
study visit. Details of each procedure and assessment can be found in Sections 6.1 and 6.2. 
The timing of each study visit is relative to the day of enrollment (Baseline Visit). 
Unscheduled visits may be performed as necessary, and may include procedures or 
assessments deemed necessary by the investigator. 
6.4.1 
Baseline Visit 
The Baseline Visit may coincide with the final visit of the MTI-103, MTI-105, MTI-106, or 
MTI-109 studies. 
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The following procedures are to be performed at the Baseline Visit (Day 1): 
• Obtain written informed consent prior to any protocol-mandated procedures (must be 
obtained prior to any other assessments) 
• Confirm subject’s eligibility based on the inclusion/exclusion   
• Collect demographic information (when permitted by regional laws or guidelines: sex, 
date of birth, race/ethnicity)  
• Collect any concomitant medications 
• Review and record subject’s medical history, including ongoing TEAEs from prior study 
(if applicable) 
• Perform complete physical examination (including height and weight)  
• Obtain ECG  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Draw blood for clinical laboratory tests (exception: participants in MTI-103, MTI-105, 
MTI-106, and MTI-109 who have had these labs in prior 14 days, in the context of that 
study) 
- 
Hematology 
- 
Chemistry 
- 
Reproductive endocrine labs for females under 55 years of age at consent  
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
PROMIS-PIQ 
- 
DLQI 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Register Baseline Visit into the Interactive Web Response System (IWRS)  
• Dispense study drug 
• Confirm next scheduled visit date 
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6.4.2 
Week 4 Visit 
The Week 4 Visit occurs 28 days (±7 days) after the Baseline Visit. At the Week 4 Visit, the 
following procedures and assessments are to be performed:  
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.3 
Week 8 Visit 
The Week 8 Visit occurs 56 days (±7 days) after the Baseline Visit. At the Week 8 Visit, the 
following procedures and assessments are to be performed:  
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
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• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.4 
Week 12 Visit 
The Week 12 Visit occurs 84 days (±7 days) after the Baseline Visit. At the Week 12 Visit, 
the following procedures and assessments are to be performed:  
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.5 
Week 20 Visit 
The Week 20 Visit occurs 140 days (±7 days) after the Baseline Visit. At the Week 20 Visit, 
the following procedures and assessments are to be performed:  
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• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
PROMIS-PIQ 
- 
DLQI 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.6 
Week 28 Visit 
The Week 28 Visit occurs 196 days (±7 days) after the Baseline Visit. At the Week 28 Visit, 
the following procedures and assessments are to be performed:  
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Reproductive endocrine labs for females under 55 years of age at consent  
- 
Hematology 
- 
Chemistry 
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• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.7 
Week 36 Visit 
The Week 36 Visit occurs 252 days (±7 days) after the Baseline Visit. At the Week 36 Visit, 
the following procedures and assessments are to be performed:  
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
PROMIS-PIQ 
- 
DLQI 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
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6.4.8 
Week 44 Visit 
The Week 44 Visit occurs 308 days (±7 days) after the Baseline Visit. At the Week 44 Visit, 
the following procedures and assessments are to be performed:  
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.9 
Week 52 Visit 
The Week 52 Visit occurs 364 days (±7 days) after the Baseline Visit. At the Week 52 Visit, 
the following procedures and assessments are to be performed:  
• Register visit into the IWRS 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Reproductive endocrine labs for females under 55 years of age at consent  
- 
Hematology 
- 
Chemistry 
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• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
PROMIS-PIQ 
- 
DLQI 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug 
• Confirm next scheduled visit date 
 
6.4.10 
Early Treatment Discontinuation Visit/Post-Drug Observation 
The Early Treatment Discontinuation (ETD) Visit occurs within 28 days of last dose for 
subjects who discontinue serlopitant treatment prior to Week 52.  
The Post-Drug Observation Visit occurs 28 days (±7 days) after the Week 52 Visit.  
At the ETD/Post-Drug Observation Visit, the following procedures and assessments are to be 
performed:  
• Register visit into the IWRS 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination with weight 
• Obtain ECG (ETD only) 
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
• Ask subject to complete WI-NRS 
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• Ask the subject to complete the following questionnaires (ETD only): 
- 
PROMIS-PIQ 
- 
DLQI 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography, ETD only) 
• Collect returned study drug (ETD only) 
 
6.4.11 
Early Termination 
Early termination of a subject from the study may occur due to loss to follow-up or 
withdrawal of consent by the subject. In accordance with legal requirements and 
International Conference on Harmonization (ICH) – Good Clinical Practice (GCP) 
guidelines, every subject or his/her legal representative has the right to withdraw from the 
study at any time and without providing reasons. If provided, the reason (adverse event, 
study burden, lack of efficacy, other) a subject withdrew consent will be recorded in the 
electronic Case Report Form (eCRF). Attempts to contact subjects who are suspected of 
being lost to follow-up must be documented in the subject’s source documents. 
7 
ASSESSMENT OF SAFETY 
7.1 
Definitions 
7.1.1 
Adverse Event 
An AE is any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. An AE can be any unfavorable and unintended sign 
(e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a drug, without any judgment about causality. 
AEs include treatment emergent exacerbations of pre-existing illnesses and AEs that occur as 
a result of protocol-mandated interventions. 
7.1.2 
Serious Adverse Event  
An AE is considered “serious” if it results in any of the following outcomes: 
• Death 
• Life-threatening AE (i.e. the subject was at immediate risk of death from the event as it 
occurred. An event that might have led to death if it had occurred with greater severity is 
not “life-threatening”) 
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• Inpatient hospitalization or prolongation of existing hospitalization  
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• Congenital anomaly/ birth defect 
• Important medical event (i.e. an event that may not result in death, be life-threatening, or 
require hospitalization, but which may be considered serious by the investigator or 
Sponsor, as it may jeopardize the subject and may require medical/surgical intervention 
to prevent one of the outcomes listed above). Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, 
blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse. 
 
The following are not considered SAEs: a visit to the emergency room or other hospital 
department < 24 hours that does not result in admission (unless considered an important 
medical or life-threatening event), an elective surgery planned prior to signing consent, 
admission as per protocol for planned medical/surgical procedure, and/or routine health 
assessments requiring admission for baseline/trending of health status (e.g. routine 
colonoscopy). 
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an 
AE (e.g. mild, moderate, or severe pain); the event itself may be of minor medical 
significance (e.g. severe back pain). “Serious” is a regulatory definition, as defined above. 
Seriousness (not severity) serves as the basis for defining regulatory reporting obligations.  
Severity and seriousness should be independently assessed when recording AEs and SAEs on 
the eCRF. 
7.1.3 
Abnormal Physical Exam, Laboratory, Vital Sign, and Electrocardiogram 
Findings  
Abnormal physical exam findings that are clinically significant and are identified prior to the 
first dose of study drug should be recorded as medical history. New or worsening clinically 
significant abnormal physical exam findings identified after the first dose of study drug 
should be recorded as AEs.   
Only abnormal laboratory, vital sign, and ECG findings that are considered clinically 
significant by the investigator (e.g. require active management or are associated with 
accompanying symptoms/signs) will be recorded as medical history or AEs on the eCRF. 
Abnormal laboratory, vital sign, and ECG findings that occur prior to the first dose of study 
drug should be recorded as medical history, and abnormal findings that occur after the first 
dose of study drug should be recorded as AEs. 
If the clinically significant laboratory, vital sign, or ECG abnormality is a sign associated 
with a confirmed disease or condition (e.g. elevated creatinine in a subject diagnosed with 
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chronic kidney disease), only the diagnosis (chronic kidney disease) needs to be recorded on 
the AE eCRF (rather than listing individual test findings as AEs).  
Separate instances of the same clinically significant laboratory, vital sign, or ECG 
abnormality across visits should not be recorded as separate AEs or SAEs. 
7.1.4 
Deaths 
Any deaths that occur from the time of informed consent to the follow-up visit, regardless of 
attribution, must be reported within 24 hours of investigator’s awareness of the death. See 
Safety Form Completion Instructions for complete instructions. 
The Sponsor should be provided a copy of any post-mortem findings and/or relevant medical 
reports, including histopathology. 
7.1.5 
Pregnancies and Contraception Requirements for Females 
For the purposes of this study, a female of childbearing potential is defined as any female 
who has experienced menarche and is pre-menopausal; a post-menopausal state is defined as 
no menses for 12 months without an alternative medical cause in a previously menstruating 
female.  
For the purposes of this study, acceptable contraception is defined below based on 
Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals: ICH M3(R2) dated January 2010, and other available 
guidelines (“U.S. Medical Eligibility Criteria for Contraceptive Use” 2010; 
“Recommendations related to contraception and pregnancy testing in clinical trials” 2014; 
“M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals” 2010):  
All female subjects of childbearing potential must use highly effective contraception, which 
includes the use of one or more of the following acceptable methods:  
1. Surgical sterilization (e.g., bilateral tubal occlusion or ligation, hysterectomy, bilateral
salpingectomy, bilateral oophorectomy)
2. Total (as opposed to periodic or cyclic) abstinence from heterosexual intercourse
3. Hormonal contraception associated with consistent inhibition of ovulation; these may
include (but are not necessarily limited to) oral, intravaginal, implantable, injectable, or
transdermal delivery methods.
a.
Progesterone only oral contraceptives are excluded as a highly effective method, as
they do not consistently inhibit ovulation.
4. Intrauterine device/system
5. Exclusive monogamous intercourse with a sterilized (i.e., vasectomized) or otherwise
non-fertile (e.g., castrated) male partner
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Any pregnancy occurring in a female subject or the female partner of a male subject, from 
the first study drug administration through the 4-week follow-up visit must be reported 
within 24 hours of the investigator’s awareness of the pregnancy. See Safety Form 
Completion Instructions for complete instructions.  
The investigator will follow the pregnancy to delivery or other pregnancy outcome.  
Pregnancy in a female clinical trial subject or female partner of a male clinical trial subject is 
not an SAE per se. Complications of such pregnancies (for example, spontaneous abortion) 
may qualify as SAEs and should be reported as such even if they occur after the Follow-up 
visit. Any congenital anomalies/birth defects must be recorded and reported as SAEs. See 
Safety Form Completion Instructions for complete instructions.  
7.1.6 
Worsening of Pruritus or Underlying Pruritic Skin Disease 
Pruritus or the underlying pruritic skin disease (PN, AD, or psoriasis) should be recorded as 
an AE or SAE only if considered by the investigator to have worsened in severity beyond the 
subject’s typical fluctuations. It is important to include a description of the nature of the 
unexpected worsening when recording the AE or SAE (e.g. new PN lesions in previously 
uninvolved skin). 
7.2 
Methods and Timing for Recording and Reporting Adverse Events 
7.2.1 
Adverse Event Reporting Period 
Any AE occurrence during the study must be recorded on source documentation and eCRF at 
the site, in accordance with protocol instructions.  
AEs and SAEs will be recorded from the first study drug administration through the follow-
up visit. After the 4-week follow-up visit, only SAEs that are believed to be drug-related 
should be reported. 
After informed consent, but prior to initiation of study drug, only SAEs considered by the 
investigator to be caused by a protocol-mandated intervention will be collected (e.g. SAEs 
related to invasive procedures such as blood collection). These procedure-related SAEs 
should only be reported on the source documents and SAE form, not on the AE eCRF. 
Subjects who undergo Baseline visit procedures but are not enrolled into the study will not 
have SAEs recorded in the clinical database. 
7.2.2 
Eliciting Adverse Events 
Investigators will seek information on AEs and SAEs at each subject contact through the 
follow-up visit. All AEs and SAEs, whether reported by the subject or noted by authorized 
study personnel, will be recorded in the subject’s medical record and on the AE eCRF page, 
and, if serious, on the SAE form. For each AE and SAE recorded, the investigator will make 
an assessment of seriousness, severity, and causality. 
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7.2.3 
Assessment of Severity 
All AEs entered into the eCRF will be graded for severity using the National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 (“Common 
Terminology Criteria for Adverse Events (CTCAE)” 2010) to describe the maximum 
intensity of the adverse event.   
If the AE cannot be found in the event-specific NCI CTCAE grading criteria, the investigator 
should use the definitions for Grade 1, 2, 3, and 4 in Table 1. 
 Table 1 
Adverse Event Grading 
Grade 
Severity 
Alternate Descriptiona 
1 
Mild (apply event-specific NCI 
CTCAE grading criteria) 
Asymptomatic or mild symptoms; clinical or 
diagnostic observations only; intervention not 
indicated. 
2 
Moderate (apply event-specific NCI 
CTCAE grading criteria) 
Minimal, local or noninvasive intervention 
indicated; limiting age-appropriate 
instrumental activities of daily living (ADLb) 
3 
Severe (apply event-specific NCI 
CTCAE grading criteria) 
Severe or medically significant but not 
immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; 
disabling; limiting self care ADLc 
4 
Very severe, life threatening, or 
disabling (apply event-specific NCI 
CTCAE grading criteria) 
Life-threatening consequences; urgent 
intervention indicated. 
5 
Death related to AE 
a 
Use these alternative definitions for Grade 1, 2, 3, and 4 events when the observed or reported AE is not in 
the NCI CTCAE listing. A semi-colon indicates ‘or’ within the alternate description of the grade. 
b 
Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
c 
Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden. 
Source: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 
Note that severity, a measure of intensity, is not equivalent to seriousness, a regulatory 
definition of outcome. Regardless of severity, some AEs may meet the criteria for 
seriousness. See Section 7.1.2 for the definition of an SAE. 
If an adverse event changes in severity during the same study period (e.g., treatment period), 
only the highest severity grade will be recorded on the eCRF.  
7.2.4 
Assessment of Causality 
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious). An investigator’s causality assessment is the determination of whether there exists a 
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reasonable possibility that the investigational product caused or contributed to an AE. 
Causality of an AE will be assessed by the investigator using the following terms: 
• Likely Related: A reaction that follows a reasonable temporal sequence from 
administration of the study drug; that follows a known or expected response pattern to the 
suspected study drug; and for which other potential etiologies are considered less likely 
factors than the study drug. 
• Likely Unrelated: A reaction that, considering all potential etiologies, is most likely due 
to factors other than the study drug. 
 
7.3 
Follow-up of Adverse Events and Serious Adverse Events 
The investigator must make every effort to follow all AEs and SAEs regardless of attribution 
until judged resolved or stabilized, the subject is lost to follow-up, or it has been determined 
that treatment with study drug or participation in the study is not the cause of the AE or SAE. 
7.4 
Reporting Serious Adverse Events to the Sponsor and Institutional 
Review Board (IRB) or Ethics Committee (EC)  
The Sponsor or designee is under obligation to report certain SAEs to regulatory authorities 
related to investigational drugs in clinical trials. The Sponsor or designee must be notified 
within 24 hours of an AE when the investigator determines that an AE meets the protocol 
definition of an SAE, regardless of the cause or relationship to study drug.  
An SAE related to study participation occurring before study drug administration and after 
informed consent should be promptly reported to the Sponsor. If the investigator learns of 
any SAE at any time after a participant has been discharged from the study, and the SAE is 
considered likely related to study drug, the SAE should be promptly reported to the Sponsor. 
Please see the Safety Form Report Completion Instructions for safety reporting instructions.  
The investigator must also comply with applicable requirements concerning reporting of 
SAEs to the IRB or EC. This may include initial or follow-up notification of an SAE or other 
safety information. 
7.5 
Reporting Serious Adverse Events to Regulatory Authorities and Study 
Investigators 
The Sponsor, or its designee, is responsible for submitting reports of serious, unexpected 
related adverse events to regulatory authorities on an expedited basis, according to the ICH 
E2A Guideline and to other regulatory authorities according to national and local regulations 
as required. The Sponsor, or its designee, is responsible for prompt submission to the IRB or 
EC of any expedited SAE reports submitted to regulatory authorities. All investigators 
participating in ongoing clinical studies with serlopitant will receive copies of the SAE 
reports submitted on an expedited basis to regulatory authorities. 
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8 
STATISTICAL METHODS  
All statistical processing will be performed using SAS® unless otherwise stated. No interim 
analyses are planned. Data will be summarized with descriptive statistics by visit. For 
continuous variables, the following information will be presented: n, mean, standard 
deviation, median, minimum and maximum. For categorical variables, counts and 
percentages will be used. 
Baseline will be the last recorded value prior to the start of treatment.  
A SAP describing all statistical analyses will be written as a separate document. 
8.1 
Handling of Missing Data and Excluded Therapy Use  
Summary statistics will generally be reported based upon observed data. Should a 
determination of treatment period (on treatment, pre-treatment) be required for adverse 
events or concomitant medication but the corresponding date is missing, or is a partial date, 
the event/medication will be considered on treatment unless the portions of the date that are 
available indicate this is not possible. 
8.2 
Analysis Population  
All subjects who receive at least 1 confirmed dose of study drug and have at least 1 post-
baseline safety assessment will be included in the safety population. All analyses will be 
performed using the safety population.   
8.3 
Subject Disposition  
An accounting of all subjects by disposition will be presented. Subjects who discontinue 
study drug prematurely or withdraw from the study will be summarized and listed, with a 
description of the reason for early termination/withdrawal. 
8.4 
Subject Characteristics  
Demographic and other baseline characteristics will be summarized. 
8.5 
Concomitant Medications  
Concomitant medications will be coded by the World Health Organization Drug Dictionary 
to Anatomical Therapeutic Classification (ATC) and preferred drug name. Concomitant 
medications will be summarized by ATC level and preferred drug name and listed. 
8.6 
Treatment Compliance and Extent of Exposure  
Compliance with study drug dosing will be determined based on tablet counts recorded on 
the eCRF. Compliance will be calculated by analyzing expected number of tablets returned 
versus actual number of tablets returned. Summaries of treatment exposure will also be 
produced.  
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8.7 
Efficacy Analyses  
Descriptive statistics will be used to summarize the following: 
• Changes from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52  
• Changes from baseline in PROMIS-PIQ score for Itch (General, Scratching Behavior, 
Mood and Sleep, Activity and Clothing) to Weeks 20, 36, and 52 
• Changes from baseline in DLQI (symptoms and feelings, daily activities, leisure, work or 
school performance, personal relationships, and treatment) to Weeks 20, 36 and 52 
• Changes from baseline in IGA PN-S to Weeks 4, 8, 20, 28, 36, 44, and 52.   
 
Data will be summarized by time point using frequency tabulations or descriptive statistics as 
appropriate. Observed results, as well as change from baseline will be summarized, as 
appropriate. 
8.8 
Safety Analyses  
8.8.1 
Adverse Events  
All AEs will be classified by system organ class and preferred term using the Medical 
Dictionary for Regulatory Activities (MedDRA). TEAEs will be tabulated in a manner which 
provides information about the incidence of TEAEs for the entire treatment period as well as 
by time period in order to understand the evolution of TEAEs over time. Thus, in addition to 
the TEAE analysis over the entire 12-month treatment time, results will be presented for the 
following periods: 0 to 4 weeks, > 4 to 12 weeks, > 12 to 28 weeks, > 28 weeks to 36 weeks, 
> 36 to end of treatment, and end of treatment to end of the study. Additionally, the pre-
specified TEAEs and SAEs that may be associated with physical dependence will be 
summarized separately. For incidence reporting, if a subject reported more than one TEAE 
that was coded to the same system organ class or preferred term, the subject will be counted 
only once for that specific system organ class or preferred term. An overview of AEs, which 
includes subject incidence of AEs, TEAEs, treatment-related TEAEs, TEAEs by severity, 
SAEs, deaths, and AEs leading to discontinuation, will be presented.  
All information pertaining to AEs noted during the study will be listed by subject and will 
include a verbatim description of the event as reported by the investigator, as well as the 
preferred term, system organ class, start date, end date (if ended), seriousness, severity, 
action taken regarding the study drug, outcome, and relationship to the study drug. In 
addition, a listing of subjects who prematurely discontinue from the study due to AEs will be 
provided. 
SAEs will be listed and summarized in a similar manner to AEs. 
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8.8.2 
Clinical Safety Laboratory Results  
Clinical safety laboratory values will be measured by a central laboratory. Summary statistics 
for actual values and for changes from baseline will be tabulated for laboratory results by 
scheduled visit. Graphs of laboratory values over time will also be produced, and listings will 
be provided.  
Subjects with clinical laboratory values outside of the normal reference range at any post-
baseline assessment will be summarized. Shifts from baseline laboratory values will be 
tabulated. A listing of all out-of-range laboratory test results, including assessment of clinical 
significance, will also be provided. 
8.8.3 
Vital Signs  
The observed vital sign data and change from baseline for each scheduled visit will be 
summarized with descriptive statistics, and presented in a listing.  
8.8.4 
Electrocardiograms  
The overall ECG assessment (abnormal or normal) and parameters will be summarized along 
with a summary of how many subjects developed a post-treatment abnormal result, and will 
be presented in a listing. 
8.8.5 
Physical Exams  
Physical exam findings will be recorded by the sites within medical history or adverse events 
and otherwise not summarized, with the exception of weight and change from baseline in 
weight. 
9 
ADMINISTRATIVE ASPECTS 
9.1 
Changes to the Protocol 
Protocol amendments must be made only with the prior written approval of the Sponsor. An 
investigator signature will be obtained for the initial protocol and any amendments. 
Substantial amendments will be provided to the appropriate regulatory authorities. No 
protocol changes affecting the following will be made without the written approval of the 
Sponsor and the responsible IRB or EC: 
• Safety and/or eligibility of subjects 
• Data integrity 
• Study design or conduct 
• Willingness of a subject to participate in the study 
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9.2 
Study Termination 
The Sponsor has the right to terminate this study at any time. Reasons may include, but are 
not limited to, evidence of a potential safety risk in this study or other serlopitant studies or 
poor enrollment. A written statement fully documenting the reasons for study termination 
will be provided to the IRB or EC. 
9.3 
Monitoring and Auditing Procedures 
The Sponsor will designate study monitors who will be responsible for monitoring the 
conduct of this study. A separate study Monitoring Plan will include details regarding the 
responsibilities of the study monitors, investigator responsibilities in providing access to 
records and addressing issues identified, the frequency and structure of monitoring visits, and 
adherence to subject confidentiality as outlined in the Informed Consent Form (ICF). 
9.4 
Transfer of Obligations 
The Sponsor will delegate certain aspects of study oversight to Contract Research 
Organizations (CROs). The specific responsibilities will be detailed in Transfer of 
Obligations documents.  
9.5 
Informed Consent 
The purpose of the study, the procedures to be carried out, and any potential risks of study 
participation will be described in non-technical terms in the ICF. After having reviewed and 
understood the ICF, subjects will be required to read, sign, and date an IRB-approved or EC-
approved consent form before any study-specific procedures are carried out. Subjects will be 
assured that they may withdraw from the study at any time without jeopardizing medical care 
related to or required as a result of study participation. The original signed consent form will 
be maintained in the investigator site file. Copies of signed consent forms will be provided to 
the subject. 
9.6 
Communication with the Institutional Review Board or Ethics Committee 
The IRB or EC is constituted and operates in accordance with the principles and 
requirements described in the ICH E6(R2) guideline. The protocol, ICF, other written subject 
information, and any proposed study advertising material must be submitted to the IRB or 
EC for written approval. IRB or EC approval of these documents will be provided to the 
investigator. The study will not start until the IRB or EC has granted its approval of the study 
materials and procedures. 
Protocol amendments will be submitted to the IRB or EC as explained in Section 9.1. SAE 
information will be submitted to the IRB or EC as explained in Section 7.4.  
If the study is terminated by the Sponsor, a written statement fully documenting the reason(s) 
for study termination will be provided to the IRB or EC. 
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9.7 
Disclosure and Confidentiality 
By signing this protocol, the investigator agrees to keep all information provided by the 
Sponsor in strict confidence and to require the same confidentiality from site staff and the 
IRB or EC. Study documents provided by the Sponsor (e.g. protocol, Investigator Brochure, 
eCRFs) will be stored appropriately to ensure their confidentiality. The information provided 
by the Sponsor to the investigator may not be disclosed to others without direct written 
authorization from the Sponsor, except to the extent necessary to obtain informed consent 
from subjects who wish to participate in the study.  
The investigator must ensure that the subjects be identified by a unique subject study 
number. Other study-related documents that may contain confidential participant information 
(e.g. signed ICFs) will be kept in strict confidence by the investigator and be stored in a 
secure location with access restricted to the study staff. 
9.8 
Records and Electronic Case Report Forms 
All study data except central laboratory and ECG data will be recorded in an eCRF system. 
Data will be entered at the site by the appropriately designated and trained site personnel. All 
source documents from which eCRF entries are derived should be placed in the subject’s 
medical records. eCRFs will be completed for every subject screened in the study. The 
investigator/institution should maintain adequate and accurate source documents and trial 
records that include all pertinent observations on each of the site’s trial subjects. Source data 
should 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 (e.g., via an audit trail). 
The study monitor will review all eCRFs in detail and will have access to participant medical 
records, laboratory data, and other source documentation to allow required eCRF fields to be 
verified by source data. 
Data consistency and plausibility checks against data entered into the eCRF will be included 
in the eCRF system. Data corrections can be performed in the eCRFs by the site. For each 
instance of data modification, the system requires a reason for change. The system keeps a 
full audit trail of the data values, the date and time of modification, and the electronic 
signature of the user who performed the change. 
After a full review of the eCRFs by the study monitor and resolution of any data 
clarifications, the investigator will review, sign, and approve the subject’s eCRF. All 
essential documents, source data, clinical records, and laboratory data will be retained by the 
site in accordance with the ICH E6(R2) guideline and the site’s data retention policies. These 
records must be available for inspection by the Sponsor, monitor, and regulatory authorities. 
Furthermore, the investigators/institutions will permit trial-related monitoring, audits, EC 
review, and inspections by a competent authority as necessary and provide direct access to 
source data/documents. 
Further detail regarding data management and eCRFs is included in the Data Management 
Plan. 
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9.9 
Good Clinical Practice and Ethical Study Conduct 
The study procedures outlined in this protocol will be conducted in accordance with 
applicable ICH Guidelines, including ICH E6(R2): Good Clinical Practice. As this study is 
conducted under a US IND, the investigator will also ensure that the basic principles of 
“Good Clinical Practice”, as outlined in 21 CFR 312, subpart D, “Responsibilities of 
Sponsors and Investigators”, 21 CFR, part 50 and 21 CFR, part 56 are adhered to. 
The study procedures outlined in this protocol will also be conducted in accordance with the 
principles of the Declaration of Helsinki. 
9.10 
End of Study Notification 
The Sponsor will notify appropriate regulatory authorities and the IRB or EC within 90 days 
from the end of the clinical study. The end of the clinical study is defined as the last study 
visit for the last subject. 
9.11 
Publication of Results 
All publications (e.g. manuscripts, abstracts, oral/slide presentations, book chapters) based on 
this study or relying on data from this study must be submitted to the Sponsor for review and 
release before submission for publication. The Sponsor is responsible for final approval of all 
publications. 
9.12 
Final Report 
A clinical trial summary report will be provided to the appropriate regulatory authorities 
within one year of the end of the clinical study. 
 
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10 
REFERENCES  
Akiyama T, Nguyen T, Curtis E, et al. A central role for spinal dorsal horn neurons that 
express neurokinin-1 receptors in chronic itch. Pain. 2015;156(7):1240-6. 
Andoh T NT, Satoh M, Kuraishi Y. Substance P induction of itch-associated response 
mediated by cutaneous NK1 tachykinin receptors in mice. J Pharmacol Exp Ther. 
1998;286(3):1140-1145. 
Booken N, Heck M, Nicolay JP, et al. Oral aprepitant in the therapy of refractory pruritus in 
erythrodermic cutaneous T-cell lymphoma. Br J Dermatol. 2011;164(3):665-67. 
Carstens EE, Akiyama T. Central mechanisms of itch. Curr Probl Dermatol. 2016;50:11-17. 
Chuquilin M, Yazan Alghalith, Fernandez KH. Neurocutaneous disease: Cutaneous 
neuroanatomy and mechanisms of itch and pain. J Am Acad Dermatol. 
2016;74:197-212.  
Common Terminology Criteria for Adverse Events (CTCAE). 4.03 ed: National Institutes of 
Health; 2010. 
Duval A, Dubertret L. Aprepitant as an antipruritic agent? N Eng J Med. 
2009;361:1415-1416. 
El-Nour H, Lundeberg L, Al-Tawil R, et al. Upregulation of the axonal growth and the 
expression of substance P and its NK1 receptor in human allergic contact dermatitis. 
Immunopharmacol Immunotoxicol. 2006;28(4):621-631. 
Emend® (aprepitant) capsule for oral use. U.S. Prescribing Information. Merck Sharp and 
Dohme Corp. Revised August 2015. 
Examples of clinical inhibitors for P450-mediated metabolisms (for concomitant use clinical 
DDI studies and/or drug labeling) (9/26/2016). U.S. Food and Drug Administration; 
2016. 
Gerber PA, Buhren BA, Cevikbas F, et al. Preliminary evidence for a role of mast cells in 
epidermal growth factor receptor inhibitor-induced pruritus. J Am Acad Dermatol. 
2010;63(1):163-165. 
Harrison S GP. Substance P. Int J Biochem. 2001;33(6):555-576. 
Hökfelt T PB, Wahren J. Substance P: A pioneer amongst neuropeptides. J Intern Med 2001; 
249:27–40. 
Ikoma A, Steinhoff M, Ständer S, et al. The neurobiology of itch. Nat Rev Neurosci. 
2006;7:535-547. 
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Lotts T, Ständer S. Research in practice: substance P antagonism in chronic pruritus. J Dtsch 
Dermatol Ges. 2014;12(7):557-559. 
Luo J, Feng J, Liu S, et al. Molecular and cellular mechanisms that initiate pain and itch. Cell 
Mol Life Sci 2015;72:3201-23. 
M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals. Food and Drug Administration; 2010. 
Recommendations related to contraception and pregnancy testing in clinical trials. Clinical 
Trial Facilitation Group; 2014. 
Santini D, Vincenzi B, Guida FM, et al. Aprepitant for management of severe pruritus related 
to biological cancer treatments: a pilot study. Lancet Oncol. 2012;13(10):1020-1024. 
Schmelz M. Itch and pain differences and commonalities. In: Schaible HG. (eds) Pain 
Control. Handbook of Experimental Pharmacology, 2015;227:285-301.   
Ständer S, Siepmann D, Herrgott I, et al. Targeting the neurokinin receptor 1 with aprepitant: 
a novel antipruritic strategy. Plos One. 2010;5(6):e10968.   
Ständer S, Weisshaar E, Raap U. Emerging drugs for the treatment of pruritus. Exp Opin 
Emerg Drugs. 2015;20:515-21. 
Steinhoff M, Bienenstock J, Schmelz M, et al. Neurophysiological, neuroimmunological, and 
neuroendocrine basis of pruritus. J Invest Dermatol. 2006;126:1705-18. 
Steinhoff MS, von Mentzer B, Geppetti P, et al. Tachykinins and their receptors: 
contributions to physiological control and the mechanisms of disease. Physiol Rev. 
2014;94(1):265-301. 
Torres T, Fernandes I, Selores M, et al. Aprepitant: Evidence of its effectiveness in patients 
with refractory pruritus continues. J Am Acad Dermatol. 2012;66(1):e14-15. 
U.S. Medical Eligibility Criteria for Contraceptive Use, 2010. Vol 20172010. 
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APPENDIX A  
SCHEDULE OF ACTIVITIES AND ASSESSMENTS 
Examination 
Baseline1 
Week 4 
(±7 
days) 
Week 8 
(±7 
days) 
 Week 
12 (±7 
days) 
Week 20 
(±7 
days) 
Week 28 
(±7 
days) 
 Week 
36 (±7 
days) 
Week 44 
(±7 
days) 
Week 52 
(±7 
days) 
Early 
Treatment 
Discontinuation 
Post-drug 
observation2 
Informed consent 
X 
  
  
  
  
  
  
  
  
 
  
I/E criteria 
X 
  
  
  
  
  
  
  
  
 
  
Demographics/ 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Physical exam3 
X4 
X 
X 
X 
X 
X 
X 
X 
X 
X4 
X4 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Labs5 
X1 
X 
  
X 
  
X 
  
  
X 
X 
X 
Urine pregnancy test6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
X 
  
  
X 
  
X 
  
X 
X 
 
WI-NRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IGA PN-S (PN 
subjects only) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PROMIS-PIQ and 
DLQI 
X 
  
  
  
X 
  
X 
  
X 
X 
 
Photographs (if 
applicable) 
X 
  
  
  
X 
  
X 
  
X 
X 
 
Dispense and/or collect 
serlopitant 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Review study drug 
compliance  
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs/SAEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1 
Baseline may coincide with the final visit of prior applicable study; Baseline labs do not need to be repeated if completed within prior 14 days 
2 
The post-drug observation visit occurs 28 days (± 7 days) after the Week 52 visit  
3 
Baseline physical exam is complete; all other physical exams are targeted 
4 
Height/weight at Baseline and weight at ETD/post-drug  
5 
Hematology and Chemistry at Baseline, Weeks 4, 12, 28, 52 and ETD/post/drug; Reproductive Endocrinology at Baseline, Weeks 28 and 52 (females 
under 55 years of age at consent) 
6 
For females of childbearing potential (with positive or equivocal results to be confirmed by a serum pregnancy test) 
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APPENDIX B  
LIST OF STRONG CYP3A4 INHIBITORS  
The list of strong CYP3A4 inhibitors is based on the United States Food and Drug Adminstration 
(FDA) list effective September 26, 2016, Examples of clinical inhibitors for P450-mediated 
metabolisms (for concomitant use clinical DDI studies and/or drug labeling (“Examples of 
clinical inhibitors for P450-mediated metabolisms (for concomitant use clinical DDI studies 
and/or drug labeling (9/26/2016)”).  
Note: This Appendix may be replaced if applicable (e.g., if updated by the FDA) through site 
communications without requiring a protocol amendment. 
1.
boceprevir
2.
clarithromycin
3.
cobicistat
4.
conivaptan
5.
danoprevir and ritonavir
6.
diltiazem
7.
elvitegravir and ritonavir
8.
regular grapefruit juice consumption
9.
idelalisib
10.
indinavir and ritonavir
11.
itraconazolea
12.
ketoconazolea
13.
lopinavir and ritonavir
14.
nefazodone
15.
nelfinavir
16.
paritaprevir and ritonavir and (ombitasvir and/or dasabuvir)
17.
posaconazolea
18.
ritonavir
19.
saquinavir and ritonavir
20.
telaprevir
21.
tipranavir and ritonavir
22.
troleandomycin
23.
voriconazolea
a 
When administered topically, it may not be considered a strong CYP3A4 inhibitor due to limited systemic 
absorption 
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Page 1 
 
CLINICAL STUDY PROTOCOL 
 
TITLE:  
AN OPEN-LABEL LONG-TERM SAFETY STUDY OF 
SERLOPITANT FOR THE TREATMENT OF PRURITUS  
IND No.: 
 
 
117780 
EudraCT: 
 
 
2017-004211-40 
ClinicalTrials.gov ID:  
TBD 
Protocol No.:  
 
MTI-107 
Protocol Version/Date: 
Version 1.1/11 April 2018 
Development Phase:  
Phase 3 
Sponsor: 
 
 
Menlo Therapeutics Inc. 
200 Cardinal Way, 2nd Floor 
Redwood City, CA 94063  
 
 
 
Confidentiality Statement: 
This document is a confidential communication of Menlo Therapeutics Inc. As such, the 
recipients agree not to disclose or reproduce, without prior written approval, this 
document and any attachments, except to appropriate Institutional Review Boards, Ethics 
Committees, representatives of the US Food and Drug Administration, the European 
Medicines Agency, other Competent Authorities or regulatory agencies, or as otherwise 
required by applicable laws or regulations. 
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SIGNATURE PAGE FOR INVESTIGATOR(S) 
 
TITLE:  
AN OPEN-LABEL LONG-TERM SAFETY STUDY OF 
SERLOPITANT FOR THE TREATMENT OF PRURITUS 
IND No.: 
 
 
117780 
EudraCT: 
 
 
2017-004211-40 
ClinicalTrials.gov ID:  
TBD 
Protocol No.:  
 
MTI-107 
Protocol Version/Date: 
Version 1.1/11 April 2018 
Development Phase:  
Phase 3 
Sponsor: 
 
 
Menlo Therapeutics Inc. 
200 Cardinal Way, 2nd Floor 
Redwood City, CA 94063  
 
 
I have read the protocol and agree to conduct this study in accordance with the protocol, all 
relevant laws and regulations in force at the time, International Conference on Harmonisation 
Guidelines for Good Clinical Practice, and the Declaration of Helsinki.  
 
 
 
Principal/Coordinating Investigator’s printed name 
 
 
 
 
 
 
Principal/Coordinating Investigator’s signature 
 
Date (DD-MMM-YYYY) 
 
  
50


SIGNATURE PAGE FOR COORDINATING INVESTIGATOR 
 
TITLE:  
AN OPEN-LABEL LONG-TERM SAFETY STUDY OF 
SERLOPITANT FOR THE TREATMENT OF PRURITUS 
IND No.: 
 
 
117780 
EudraCT: 
 
 
2017-004211-40 
ClinicalTrials.gov ID:  
TBD 
Protocol No.:  
 
MTI-107 
Protocol Version/Date: 
Version 1.1/11 April 2018 
Development Phase:  
Phase 3 
Sponsor: 
 
 
Menlo Therapeutics Inc. 
200 Cardinal Way, 2nd Floor 
Redwood City, CA 94063  
 
 
I have read the protocol and agree to conduct this study in accordance with the protocol, all 
relevant laws and regulations in force at the time, International Conference on Harmonisation 
Guidelines for Good Clinical Practice, and the Declaration of Helsinki.  
 
 
 
Date (DD-MMM-YYYY) 
 
 
 
Country of Coordinating Investigator 
 
 
 
13Apr2018
51
PPD
PPD
PPD




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PROTOCOL SYNOPSIS 
Study Title: 
An Open-Label Long-Term Safety Study of Serlopitant for the Treatment of Pruritus  
Protocol Number: 
MTI-107 
Sponsor: 
Menlo Therapeutics Inc. 
Development Phase: 
Phase 3 
Study Objectives: 
Primary objective:  
• 
To assess the long-term safety of serlopitant in adults with pruritus 
associated with prurigo nodularis (PN), atopic dermatitis (AD), or psoriasis. 
Secondary objectives:  
• 
To assess change in severity of pruritus in subjects with PN, AD, or 
psoriasis using the worst-itch numeric rating scale (WI-NRS).  
• 
To assess change in severity and extent of PN using the Investigator’s 
Global Assessment of PN Stage (IGA PN-S), for those subjects with PN. 
• 
To assess whether serlopitant produces physical dependence.  
Study Design: 
Study MTI-107 is a multicenter, open-label study to assess the long-term safety of 
serlopitant in adults with pruritus associated with PN, AD, or psoriasis. Eligible 
subjects who have completed selected studies of serlopitant may be given the 
opportunity, at the investigator’s discretion, to consent to and participate in this 
open-label study, regardless of their treatment allocation in prior studies. If deemed 
necessary by Menlo Therapeutics to meet enrollment objectives, eligible subjects 
who have not participated in a prior serlopitant study may also be enrolled in study 
MTI-107. 
The study will consist of two periods, for a total study period of approximately 
56 weeks: 
• 
Treatment period: 52 weeks 
• 
Post-drug observation period: 4 weeks 
During the treatment period, subjects will take one serlopitant 5 mg tablet once daily 
orally.  
Standard therapy for the concurrent skin lesions and pruritus may be employed 
during this study.  
After completion of the 52-week treatment period, all subjects will enter a 4-week 
post-drug observation period. Subjects who discontinue treatment early will have a 
post-drug observation visit 4 weeks after their last dose of serlopitant.  
Safety Review: 
An internal safety monitoring team consisting of representatives from Menlo 
Therapeutics Inc. and its designees will monitor safety data on a regular basis 
throughout the study. 
Planned Sample Size: 
Approximately 400 subjects  
Study Population: 
The study will enroll adults with pruritus due to PN, AD, or psoriasis. 
Inclusion Criteria (Subjects must meet the following criteria to be enrolled into the 
study):  
1. Male or female, age 18 years or older at consent. 
2. Subject reports pruritus in the 24-hour period prior to enrollment and: 
a. 
Has completed a prior applicable clinical study of serlopitant 
without a serious adverse event (SAE) that was assessed as likely 
related to the study drug  
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OR  
b. Has not participated in a prior clinical study of serlopitant and has 
a clinical diagnosis of PN, AD, or psoriasis, and Sponsor has 
approved enrollment. 
3. All female subjects who are of childbearing potential must be willing to 
practice highly effective contraception (i.e., pregnancy prevention method 
with a failure rate of <1% per year) from the time of the Baseline visit until 
2 weeks after last dose of study drug. 
4. Willing and able (has adequate cognitive ability, in the investigator’s 
opinion) to comply with study visits and study related requirements 
including providing written informed consent. 
 
Exclusion Criteria (Subjects who meet any of the following criteria are not eligible 
for participation in the study): 
1. Presence of malignancy within 5 years prior to enrollment (exception for 
non-melanoma cutaneous malignancies). 
2. Presence of a psychiatric diagnosis (such as major depressive disorder, 
bipolar disorder, schizophrenia, psychotic disorder, intellectual disability, 
severe alcohol abuse disorder) meeting Diagnostic and Statistical Manual 
of Mental Disorders, Fifth Edition criteria in past 3 years, history of 
suicidal ideation within the past 3 years or any history of suicide attempt.  
3. Presence of any medical condition or disability, that, in the investigator’s 
opinion, could interfere with the assessment of safety in this study or 
compromise the safety of the subject.  
4. Treatment with any investigational therapy within 4 weeks or 5-half-lives 
prior to enrollment (whichever is longer) or expected participation in 
another clinical study involving an investigational product or device during 
the subject’s participation in MTI-107. 
5. Treatment with other neurokinin-1 receptor (NK1-R) antagonists (e.g., 
aprepitant, fosaprepitant, rolapitant) within 4 weeks prior to enrollment. 
6. Treatment with strong cytochrome P450 3A4 inhibitors within 4 weeks 
prior to enrollment. 
7. Currently pregnant or breastfeeding or planning to become pregnant during 
the study. 
Study Drug: 
Serlopitant 5 mg tablets 
Dosage:  
Serlopitant: 5 mg once daily orally for 52 weeks  
Safety Endpoints: 
• 
Incidence of treatment-emergent adverse events (TEAEs) and SAEs 
• 
Changes from baseline in clinical laboratory parameters following study 
drug exposure 
• 
Changes from baseline in vital sign and electrocardiogram (ECG) 
parameters following study drug exposure 
• 
Assessment of physical dependence following chronic study drug exposure, 
in the monitored 4-week post-drug discontinuation period  
Efficacy Endpoints: 
• 
Changes from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52  
• 
Changes from baseline in Patient-Reported Outcomes Measurement 
Information System Itch Questionnaire (PROMIS-PIQ) score for Itch 
(General, Scratching Behavior, Mood and Sleep, Activity and Clothing) to 
Weeks 20, 36, and 52 
• 
Changes from baseline in Dermatology Life Quality Index (DLQI) 
(symptoms and feelings, daily activities, leisure, work or school 
performance, personal relationships, and treatment) to Weeks 20, 36 and 52 
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• 
Changes from baseline in IGA PN-S to Weeks 4, 8, 20, 28, 36, 44, and 52 
Statistical Methods: 
All subjects who receive at least 1 confirmed dose of study drug and have at least 1 
post-baseline safety assessment will be included in the safety population. All 
analyses will be performed using the safety population. 
Data will be summarized with descriptive statistics by visit. For continuous 
variables, the following information will be presented: n, mean, standard deviation, 
median, minimum and maximum. For categorical variables, counts and percentages 
will be used. 
All adverse events (AEs) will be classified by system organ class and preferred term 
using the Medical Dictionary for Regulatory Activities (MedDRA). TEAEs will be 
tabulated in a manner which provides information about the incidence of TEAEs for 
the entire treatment period as well as by specified time periods in order to 
understand the evolution of TEAEs over time. Additionally, the pre-specified 
TEAEs and SAEs that may be associated with physical dependence will be 
summarized separately. An overview of AEs, which includes subject incidence of 
TEAEs, treatment-related TEAEs, TEAEs by severity, SAEs, deaths, and AEs 
leading to discontinuation, will be presented.  
Summary statistics for actual safety laboratory values and for changes from baseline 
will be tabulated by scheduled visit. Subjects with clinical laboratory values outside 
of the normal reference range at any post-baseline assessment will be summarized. 
Shifts from baseline laboratory values will be tabulated. A listing of all out-of-range 
laboratory test results, including assessment of clinical significance will also be 
provided. 
The observed vital sign data and change from baseline will be summarized with 
descriptive statistics and presented in a listing. 
The overall ECG assessment (abnormal or normal) and parameters will be 
summarized along with a summary of how many subjects developed a post-
treatment abnormal result and will be presented in a listing.  
Physical exam findings will be recorded by the sites within medical history or AEs 
and otherwise not summarized, with the exception of weight, and change from 
baseline in weight. 
The WI-NRS, PROMIS-PIQ, DLQI, and IGA PN-S, will be summarized with 
descriptive statistics by visit. 
Study Sites: 
Approximately 120 study sites 
Expected Duration of 
Subject’s 
Participation 
Approximately 56 weeks: 52 weeks of treatment, and a post-drug observation period 
of 4 weeks. 
 
This study will be conducted in accordance with the Guidelines of Good Clinical Practice. 
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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ............................................................................................1 
SIGNATURE PAGE FOR INVESTIGATOR(S) .....................................................................2 
SPONSOR PROTOCOL APPROVAL SIGNATURE(S) .........................................................3 
PROTOCOL SYNOPSIS ..........................................................................................................4 
TABLE OF CONTENTS ...........................................................................................................7 
LIST OF APPENDICES ..........................................................................................................10 
LIST OF TABLES ...................................................................................................................10 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..........................................11 
1 
INTRODUCTION .................................................................................................12 
1.1 
Pruritus .............................................................................................................12 
1.1.1 
Role of Substance P and the Neurokinin-1 Receptor in Pruritus .........12 
1.2 
Serlopitant ........................................................................................................13 
1.2.1 
Serlopitant Background and Nonclinical Summary ............................13 
1.2.2 
Serlopitant Clinical Summary ..............................................................14 
1.2.3 
Serlopitant in Pruritus-Related Studies ................................................14 
2 
STUDY OBJECTIVES ..........................................................................................16 
3 
STUDY DESIGN...................................................................................................16 
3.1 
Overall Study Design .......................................................................................16 
3.2 
Rationale for Study Design and Dose Selection ..............................................17 
3.3 
Study Endpoints ...............................................................................................17 
3.3.1 
Safety Endpoints ..................................................................................17 
3.3.2 
Efficacy Endpoints ...............................................................................17 
3.4 
Safety Review ..................................................................................................18 
3.4.1 
Safety Monitoring Team ......................................................................18 
4 
SELECTION OF STUDY POPULATION ...........................................................18 
4.1 
Study Population ..............................................................................................18 
4.2 
Inclusion Criteria .............................................................................................18 
4.3 
Exclusion Criteria ............................................................................................19 
5 
STUDY DRUG ......................................................................................................19 
5.1 
Study Drug Supply, Route of Administration, and Storage.............................19 
5.2 
Labeling and Study Drug Accountability ........................................................20 
5.3 
Dosing Regimen...............................................................................................20 
5.4 
Dose Modification ...........................................................................................20 
5.5 
Missed or Delayed Doses.................................................................................20 
5.6 
Study Drug Discontinuation ............................................................................20 
5.7 
Concomitant and Excluded Therapies .............................................................21 
5.7.1 
Excluded Therapies ..............................................................................21 
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5.8 
Assignment to Treatment .................................................................................21 
5.9 
Treatment Compliance .....................................................................................22 
6 
STUDY SCHEDULE AND ASSESSMENTS ......................................................22 
6.1 
Efficacy Parameters .........................................................................................22 
6.1.1 
Itch Numeric Rating Scale ...................................................................22 
6.1.2 
Investigator’s Global Assessment of PN Stage ...................................22 
6.1.3 
Patient-Reported Outcomes Measurement Information System Itch 
Questionnaire .......................................................................................22 
6.1.4 
Dermatology Life Quality Index ..........................................................22 
6.1.5 
Photographs..........................................................................................23 
6.2 
Safety Parameters.............................................................................................23 
6.2.1 
Vital Signs ............................................................................................23 
6.2.2 
Physical Examination...........................................................................23 
6.2.3 
Clinical Laboratory Assessments .........................................................23 
6.2.4 
Electrocardiogram ................................................................................24 
6.2.5 
Assessment of Potential for Physical Dependence ..............................24 
6.3 
Subject Flow Diagram .....................................................................................24 
6.4 
Study Visits ......................................................................................................24 
6.4.1 
Baseline Visit .......................................................................................24 
6.4.2 
Week 4 Visit ........................................................................................26 
6.4.3 
Week 8 Visit ........................................................................................26 
6.4.4 
Week 12 Visit ......................................................................................27 
6.4.5 
Week 20 Visit ......................................................................................27 
6.4.6 
Week 28 Visit ......................................................................................28 
6.4.7 
Week 36 Visit ......................................................................................29 
6.4.8 
Week 44 Visit ......................................................................................30 
6.4.9 
Week 52 Visit ......................................................................................30 
6.4.10 
Early Treatment Discontinuation Visit/Post-Drug Observation ..........31 
6.4.11 
Early Termination ................................................................................32 
7 
ASSESSMENT OF SAFETY ................................................................................32 
7.1 
Definitions........................................................................................................32 
7.1.1 
Adverse Event ......................................................................................32 
7.1.2 
Serious Adverse Event .........................................................................32 
7.1.3 
Abnormal Physical Exam, Laboratory, Vital Sign, and 
Electrocardiogram Findings .................................................................33 
7.1.4 
Deaths ..................................................................................................34 
7.1.5 
Pregnancies and Contraception Requirements for Females .................34 
7.1.6 
Worsening of Pruritus or Underlying Pruritic Skin Disease ................35 
7.2 
Methods and Timing for Recording and Reporting Adverse Events ...............35 
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7.2.1 
Adverse Event Reporting Period .........................................................35 
7.2.2 
Eliciting Adverse Events......................................................................35 
7.2.3 
Assessment of Severity ........................................................................36 
7.2.4 
Assessment of Causality ......................................................................36 
7.3 
Follow-up of Adverse Events and Serious Adverse Events ............................37 
7.4 
Reporting Serious Adverse Events to the Sponsor and Institutional Review 
Board (IRB) or Ethics Committee (EC)...........................................................37 
7.5 
Reporting Serious Adverse Events to Regulatory Authorities and Study 
Investigators .....................................................................................................37 
8 
STATISTICAL METHODS ..................................................................................38 
8.1 
Handling of Missing Data and Excluded Therapy Use ...................................38 
8.2 
Analysis Population .........................................................................................38 
8.3 
Subject Disposition ..........................................................................................38 
8.4 
Subject Characteristics .....................................................................................38 
8.5 
Concomitant Medications ................................................................................38 
8.6 
Treatment Compliance and Extent of Exposure ..............................................38 
8.7 
Efficacy Analyses ............................................................................................39 
8.8 
Safety Analyses ................................................................................................39 
8.8.1 
Adverse Events ....................................................................................39 
8.8.2 
Clinical Safety Laboratory Results ......................................................40 
8.8.3 
Vital Signs ............................................................................................40 
8.8.4 
Electrocardiograms ..............................................................................40 
8.8.5 
Physical Exams ....................................................................................40 
9 
ADMINISTRATIVE ASPECTS ...........................................................................40 
9.1 
Changes to the Protocol ...................................................................................40 
9.2 
Study Termination ...........................................................................................41 
9.3 
Monitoring and Auditing Procedures...............................................................41 
9.4 
Transfer of Obligations ....................................................................................41 
9.5 
Informed Consent.............................................................................................41 
9.6 
Communication with the Institutional Review Board or Ethics Committee ...41 
9.7 
Disclosure and Confidentiality ........................................................................42 
9.8 
Records and Electronic Case Report Forms ....................................................42 
9.9 
Good Clinical Practice and Ethical Study Conduct .........................................43 
9.10 
End of Study Notification ................................................................................43 
9.11 
Publication of Results ......................................................................................43 
9.12 
Final Report .....................................................................................................43 
10 
REFERENCES ......................................................................................................44 
 
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LIST OF APPENDICES 
Appendix A  Schedule of Activities and Assessments ..........................................................46 
Appendix B  List of Strong CYP3A4 Inhibitors ...................................................................47 
 
LIST OF TABLES 
Table 1 
Adverse Event Grading ..............................................................................36 
  
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS   
Abbreviation 
Definition 
AD 
Atopic dermatitis  
ADL 
Activities of daily living 
AE 
Adverse event 
ALT 
Alanine aminotransferase  
AMH 
Anti-Mullerian hormone 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Classification 
CYP3A4 
cytochrome-P 3A4  
DLQI 
Dermatology Life Quality Index 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
ETD 
Early Treatment Discontinuation 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
FSH 
Follicle-stimulating hormone 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IGA PN-S 
Investigator’s Global Assessment of Prurigo Nodularis Stage 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System  
LDH 
Lactate dehydrogenase 
LH 
Luteinizing hormone 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NK1-R 
Neurokinin-1 receptor 
NRS 
Numeric rating scale  
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PROMIS-PIQ 
Patient-Reported Outcomes Measurement Information System Itch Questionnaire (PIQ) 
PN 
Prurigo nodularis 
QOL 
Quality of life 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan  
SP 
Substance P 
TEAE 
Treatment-emergent adverse event 
VAS 
Visual Analog Scale 
WI-NRS 
Worst-Itch Numeric Rating Scale 
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1 
INTRODUCTION 
1.1 
Pruritus  
Pruritus, or itch, is defined as an unpleasant sensation that evokes a desire to scratch 
(Ikoma 2006). Itch and pain, although closely related, are distinct sensations: itch elicits a 
scratching response, whereas pain causes a withdrawal response.  
Emerging research in neurobiology has greatly expanded the understanding of pruritus 
signaling. Pruritoceptors (itch-sensory nerve fibers) consist of two distinct classes of nerve 
fibers: histamine-responsive mechanoinsensitive C-fibers, and histamine-unresponsive 
mechanosensitive polymodal C and Aδ fibers that are activated by cowhage (highly pruritic 
spicules from the pods of the cowhage plant Mucuna pruriens) (Schmelz 2015). The second 
class of histamine-unresponsive, cowhage-responsive nerve fibers has been of particular 
interest in pruritus research, as C-fibers that have a strong and sustained response to 
histamine comprise only about 20% of the overall mechanoinsensitive C-fiber population 
(Steinhoff 2006), and a significant proportion of chronic pruritic conditions do not appear to 
involve histamine-mediated pruritus signaling (Ikoma 2006). Substance P (SP) is a prominent 
pruritogen (itch mediator) in this histamine-independent pruritus pathway (Chuquilin 2016).  
Pruritus stimuli in the skin are transmitted via sensory neurons that have their cell bodies in 
the dorsal root ganglia (DRG) and are linked to second-order neurons in the spine 
(Carstens 2016, Luo 2015). Following activation of these DRG sensory neurons, the pruritus 
signal is transmitted to the second-order spinal neurons primarily by SP, gastrin-releasing 
peptide, and glutamate in histamine-independent pruritus, and primarily by glutamate in 
histamine-mediated pruritus (Chuquilin 2016). 
Spinal itch neuron projections ascend via the contralateral spinothalamic tract to the thalamus 
and via the lateral spinoparabrachial tract to the lateral parabrachial nucleus, from which 
point they activate multiple centers in the somatosensory cortex, the premotor cortex, and the 
cingulate cortex – areas involved in the sensory processing and motor response (scratching) 
to the itch signal (Carstens 2016, Chuquilin 2016). 
1.1.1 
Role of Substance P and the Neurokinin-1 Receptor in Pruritus 
Substance P is an undecapeptide that belongs to the tachykinin family of neuropeptides, a 
group that also includes neurokinin A and neurokinin B (Hökfelt 2001). SP has been 
implicated in a number of biological functions, both physiological and pathophysiological, 
including pruritus perception, vomiting reflex, pain perception, and immunomodulatory 
responses (Lotts 2014, Andoh 1998, Steinhoff 2014).  The biological actions of SP are 
mediated by tachykinin receptors, which consist of seven hydrophobic transmembrane 
domains coupled to G-proteins. Three tachykinin receptors have been identified: the 
neurokinin-1 (NK1-R), neurokinin-2, and neurokinin-3 receptors (Harrison 2001). The 
neurokinin-1 receptor, in particular, has been studied in great detail. NK1-R is the primary 
receptor for SP in the human body, and is found on multiple cell types, including central and 
peripheral neurons, keratinocytes, mast cells, and dendritic cells (El-Nour 2006, 
Ständer 2015).  
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NK1-R stimulation has been shown to be an important pathway for pruritus perception 
(Ständer 2015). Inhibition of this pathway results in decreased pruritus and scratching 
reflexes in animal models (Akiyama 2015). Preceding the development of serlopitant for 
pruritus-related conditions, a commercially available NK1-R antagonist (Emend USPI) has 
been used as a therapy to decrease pruritus in patients with chronic pruritus due to etiologies 
such as cutaneous T-cell lymphoma (Duval 2009, Torres 2012, Booken 2011) and erlotinib-
induced pruritus (Santini 2012, Gerber 2010). Additionally, in a study of 20 patients with 
chronic pruritus of various etiologies treated with aprepitant, 16/20 patients (80%) 
experienced a considerable reduction of itch intensity (Ständer 2010).  
1.2 
Serlopitant  
1.2.1 
Serlopitant Background and Nonclinical Summary 
Serlopitant is a small molecule, highly selective NK1-R antagonist that is administered orally 
and metabolized by cytochrome-P 3A4 (CYP3A4), with a plasma half-life of 45-86 hours. It 
binds with high affinity to the human NK1-R with a dissociation constant (Kd) of 46 pM; 
displacing SP binding with a half-maximal inhibition concentration (IC50) of 61 pM. 
Serlopitant is a potent functional antagonist of SP-induced inositol phosphate generation. 
Serlopitant has been extensively studied in animal toxicology studies, including chronic 
toxicology and carcinogenicity studies. In non-clinical chronic toxicology studies in rats, 
mice and dogs, treatment related findings of potential clinical significance included increased 
salivation, decreased body weight gain and food consumption, slight changes in hematology 
and serum biochemistry parameters, mild increases in liver weight and mild 
histomorphologic changes. The histomorphologic changes were seen only in rats (not in dogs 
or mice) and included: very slight ovarian interstitial cell hypertrophy, mammary gland and 
uterine atrophy; decreased corpora lutea; increased histiocytes in lung and mesenteric lymph 
nodes; slight skeletal and cardiac muscle degeneration; slight increased hematopoiesis in 
bone marrow; and slight to moderate vacuolation in kidney tubules. These nonclinical 
findings occurred at systemic exposures exceeding those anticipated to provide efficacy of 
serlopitant for pruritus indications in humans (1 to 5 mg tablet daily). No cardiac lesions have 
been observed in dog toxicity studies up to 9 months in duration nor in a 3-month mouse 
range-finding study and 2-year mouse carcinogenicity study at exposure higher than the 
lowest level which caused cardiotoxicity in rats. The no observed adverse effect level 
(NOAEL) in rats for histomorphological changes in the reproductive tract, mammary gland 
and bone marrow provides a 2.5-fold margin for the maximum-targeted exposure (5 mg 
tablet daily). The rat NOAEL for histomorphological changes in muscle and kidney provides 
a 5-fold margin for the maximum-targeted exposure (5 mg tablet daily).  
In summary, the nonclinical toxicity noted with serlopitant provides no contraindications to 
the continuation of clinical trials via the oral route. Findings in the developmental toxicity 
studies support inclusion of women of childbearing potential in clinical trials in accordance 
with the study protocol and local regulatory guidances.  
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1.2.2 
Serlopitant Clinical Summary 
In humans, serlopitant has been administered to over 1000 individuals. Single doses up to 
400 mg have been well tolerated in young adult males and single doses up to 25 mg have 
been well tolerated in the elderly. Multiple doses of up to 50 mg a day for 4 weeks have been 
well tolerated in healthy young males, and a single (loading) dose of 15 mg followed by daily 
doses of 5 mg for 2 weeks have been well tolerated in elderly males and females. Forty-one 
(41) subjects received 4 mg liquid filled capsule (LFC) daily (bioequivalent to 5 mg tablets) 
for 1 year. Plasma concentrations of serlopitant appear to increase in a dose-proportional 
fashion in both young males and elderly subjects (males and females). Peak plasma 
concentrations after a single oral dose occurred at ~2 to 4 hours in both young and elderly 
subjects. A single loading dose of up to 15 mg followed by 6 to 8 weeks of up to 5 mg daily 
doses has been well tolerated in adults with chronic pruritus and prurigo nodularis (PN). 
Pharmacokinetic data demonstrate good plasma exposures with oral dosing, linear dose-
dependent increases in plasma concentration and systemic exposure, a plasma t1/2 
appropriate for once daily dosing, and mild effects of concomitant food ingestion. Central 
nervous system (CNS) positron emission tomography (PET) studies have demonstrated good 
CNS penetrance and > 90% NK1 receptor occupancy (RO) at plasma exposures anticipated 
to be safe and well tolerated. Three long-lived active hydroxylated metabolites are observed 
in humans: M1/M1a 
, M2/M2a 
, and M3 
. 
These metabolites were present at lower concentrations and were 2- to 9-fold less potent in 
vivo than the parent compound. The integrated pharmacokinetic/pharmacodynamic (PK/PD) 
analysis concluded that these metabolites are unlikely to contribute significantly to 
occupancy of the CNS NK1-R in humans. 
1.2.3 
Serlopitant in Pruritus-Related Studies 
Serlopitant has been evaluated in two completed Phase 2 studies of subjects with chronic 
pruritus (TCP-101 and TCP-102).  
TCP-101 
TCP-101 was a double-blind, placebo-controlled, multi-center study that compared 
serlopitant 0.25 mg, 1 mg, or 5 mg vs. placebo for the treatment of chronic pruritus. A total 
of 257 adult subjects 18-65 years of age with chronic pruritus were randomized to receive 
one of the four dose groups in a 1:1:1:1 randomization. Subjects received a loading dose of 
3 tablets on Day 1 and thereafter received 1 tablet per day for 6 weeks. The primary efficacy 
endpoint was itch severity as measured on a Visual Analog Scale (VAS), summarized as a 
percentage change from baseline. 
Mean percent decreases from Baseline in VAS score were larger in the active-treatment 
groups versus placebo at every scheduled post-baseline study visit. Overall, the results were 
the most profound for the serlopitant 1 mg and 5 mg groups. For the percent change from 
Baseline in VAS pruritus scores (the primary efficacy variable), the Week 6 pairwise least 
squares mean difference compared to placebo was 5.8 mm, 13.2 mm, and 14.2 mm for 
serlopitant 0.25 mg, 1 mg, and 5 mg, respectively.   
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The frequency of treatment-emergent adverse events (TEAEs) and study drug related adverse 
events (AEs) was higher in the serlopitant 1 mg and 5 mg groups compared to the serlopitant 
0.25 mg group, and the frequency in all three treatment groups were higher than in the 
placebo group. The frequency of AEs leading to study drug discontinuation was comparable 
in the serlopitant 5 mg and placebo group and higher than in the serlopitant 0.25 mg and 
1 mg groups. There was one serious adverse event (SAE) reported in the serlopitant 1 mg 
group (spontaneous abortion, considered not related). There were no deaths. The most 
common AEs in the serlopitant groups were diarrhea (6.2%, 1 mg group), upper respiratory 
tract infection (4.7%, 0.25 mg group), somnolence (4.7%, 5 mg group), nasopharyngitis 
(4.6%, 1 mg group), headache (4.7%, 5 mg group), urinary tract infection (3.1%, 5 mg 
group), dry mouth (3.1%, 1 mg group), nausea (3.1%, 1 mg group), arthralgia (3.1%, 0.25 
mg group), musculoskeletal pain (3.1%, 1 mg group) and pruritus (3.1%, 1 mg group). The 
most common AEs in the placebo group were headache (6.3%), nasopharyngitis (3.2%), 
upper respiratory tract infection (3.2%), urinary tract infection (3.2%) and asthma (3.2%).  
TCP-102 
TCP-102 was a randomized, double-blind, placebo-controlled multi-center study that 
evaluated serlopitant 5 mg vs. placebo for the treatment of PN A total of 128 adult subjects 
18-80 years of age with PN were randomized to receive serlopitant or placebo in a 1:1 
randomization. Subjects received a loading dose of 3 tablets on Day 1 followed by 1 tablet 
per day for 8 weeks. The primary efficacy endpoint was the average VAS score as recorded 
at the study visits. Results at Week 4 and Week 8 were the primary timepoints. 
Serlopitant 5 mg was superior to placebo for the reduction of pruritus as measured by change 
in average VAS from baseline. For the primary endpoint, change from baseline at Week 4 
and Week 8 by repeated measures analysis, the decrease from baseline was significantly 
greater in the serlopitant group than the placebo group, with a mean difference (serlopitant 
minus placebo) of -1.0 at Week 4 and -1.7 at Week 8. The mean difference at Week 2 was 
also significant, -0.9. In a post-hoc analysis of the percentage of subjects who were 4-point 
responders on average VAS at Week 8, 25.0% of placebo subjects and 54.4% of serlopitant 
subjects were 4-point responders. 
TEAEs were reported for 71.9% of serlopitant-treated subjects and 61.9% of placebo-treated 
subjects. The most frequently reported TEAEs in the serlopitant group were nasopharyngitis 
(17.2% serlopitant, 3.2% placebo), diarrhea (10.9% serlopitant, 4.8% placebo), and fatigue 
(9.4% serlopitant, 6.3% placebo). Treatment-related TEAEs were reported for 48.4% of 
serlopitant-treated subjects and 34.9% of placebo-treated subjects. The most frequently 
reported treatment-related TEAEs in the serlopitant group were fatigue (7.8%) and diarrhea, 
peripheral edema, dizziness, and headache (each 6.3%). Most TEAEs were mild or moderate; 
severe TEAEs were reported for 9.4% of serlopitant-treated subjects and 4.8% of placebo-
treated subjects. There were no deaths during the study. Five subjects (3 serlopitant, 
2 placebo) had SAEs. The SAEs were actinic elastosis, depression, dizziness, and vertigo in 
the serlopitant group; and bradycardia, syncope, respiratory failure, and neurodermatitis in 
the placebo group. Nine subjects (3 serlopitant, 6 placebo) discontinued due to TEAEs. 
No clinically relevant changes were observed in chemistry, hematology, vital signs, or 
electrocardiogram (ECG) results. 
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The results of the Phase 2 studies in PN and chronic pruritus, together with the extensive 
nonclinical and clinical safety data and experience with serlopitant to date and the scientific 
rationale for NK1-R inhibition in the treatment of pruritus, serve to support further evaluation 
of serlopitant for the long-term treatment of pruritus in patients with PN, AD, or psoriasis. 
The potential benefits of continued clinical study outweigh the potential risks. The data 
obtained from this long-term study will inform the risks and benefits of long-term exposure 
(chronic or repeated intermittent use for longer than 6 months). The risk to subjects in this study 
will be minimized by medical and safety monitoring (see Section 3.4.1). 
 
Please refer to the Investigator’s Brochure for further information regarding serlopitant. 
2 
STUDY OBJECTIVES  
The primary objective of this study is to assess the long-term safety of serlopitant in adults 
with pruritus associated with PN, AD, or psoriasis. 
The secondary objectives of this study are to assess the change in severity of pruritus in 
subjects with PN, AD, or psoriasis using the worst-itch numeric rating scale (WI-NRS); to 
assess the change in severity and extent of PN using the Investigator’s Global Assessment of 
PN Stage (IGA PN-S), for those subjects with PN; and to assess whether serlopitant produces 
physical dependence. 
3 
STUDY DESIGN 
3.1 
Overall Study Design 
This is a multicenter, open-label study to assess the long-term safety of serlopitant in adults 
with pruritus associated with PN, AD, or psoriasis. Eligible subjects who have completed 
selected studies of serlopitant may be given the opportunity, at the investigator’s discretion, 
to consent to and participate in this open-label study, regardless of their treatment allocation 
in prior studies. If deemed necessary by Menlo Therapeutics to meet enrollment objectives, 
eligible subjects who have not participated in a prior serlopitant study may also be enrolled in 
study MTI-107. Approximately 120 study sites may enroll subjects in this long-term safety 
study. 
This study will consist of two periods, for a total study period of approximately 56 weeks: 
• Treatment period: 52 weeks 
• Post-drug observation period: 4 weeks 
 
During the treatment period, subjects will take one serlopitant 5 mg tablet once daily orally 
(Section 5.3).  
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Standard therapy for the concurrent skin lesions and pruritus may be employed during this 
study (Section 5.7.1).  
The WI-NRS during a 24-hour recall period will be assessed by the subject at each study 
visit. 
For those subjects with PN, the severity and extent of PN will be assessed at selected visits, 
using the IGA-PN-S, and photographs of representative areas with PN will be taken at 
selected visits at a subset of sites. 
The Patient-Reported Outcomes Measurement Information System Itch Questionnaire 
(PROMIS-PIQ) and the Dermatology Life Quality Index (DLQI) will be administered at 
selected visits. 
After completion of the 52-week treatment period, all subjects will enter a 4-week post-drug 
observation period. Subjects who discontinue treatment early will have a post-drug 
observation visit 4 weeks after their last dose of serlopitant. During this monitored 
discontinuation period, solicited safety evaluations will assess the potential for serlopitant to 
produce physical dependence. 
3.2 
Rationale for Study Design and Dose Selection 
The current MTI-107 study is designed to confirm the long-term safety of serlopitant for the 
treatment of pruritus in patients with PN, AD, and psoriasis. The 5 mg dose of serlopitant 
was selected for this study based on the favorable efficacy, safety, and tolerability profile of 
serlopitant at this dose level in completed studies.  
3.3 
Study Endpoints 
3.3.1 
Safety Endpoints 
The safety endpoints are as follows: 
• Incidence of TEAEs and SAEs 
• Changes from baseline in clinical laboratory parameters following study drug exposure 
• Changes from baseline in vital sign and ECG parameters following study drug exposure 
• Assessment of physical dependence following chronic study drug exposure, in the 
4-week post-drug discontinuation period.  
 
3.3.2 
Efficacy Endpoints 
The efficacy endpoints are as follows: 
• Changes from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52  
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• Changes from baseline in PROMIS-PIQ score for Itch (General, Scratching Behavior, 
Mood and Sleep, Activity and Clothing) to Weeks 20, 36, and 52 
• Changes from baseline in DLQI (symptoms and feelings, daily activities, leisure, work or 
school performance, personal relationships, and treatment) to Weeks 20, 36 and 52 
• Changes from baseline in IGA PN-S to Weeks 4, 8, 20, 28, 36, 44, and 52 
 
3.4 
Safety Review 
3.4.1 
Safety Monitoring Team 
An internal safety monitoring team consisting of representatives from Menlo Therapeutics 
Inc. and its designees will monitor safety data on a regular basis throughout the study. 
4 
SELECTION OF STUDY POPULATION 
4.1 
Study Population 
Approximately 400 adult subjects with pruritus due to PN, AD, or psoriasis will be enrolled 
in this study. 
4.2 
Inclusion Criteria 
Subjects must meet the following criteria to be enrolled into the study: 
1. Male or female, age 18 years or older at consent. 
2. Subject reports pruritus in the 24-hour period prior to enrollment and: 
a. Has completed a prior applicable clinical study of serlopitant without an SAE that 
was assessed as likely related to the study drug  
OR  
b. Has not participated in a prior clinical study of serlopitant and has a clinical diagnosis 
of PN, AD, or psoriasis, and Sponsor has approved enrollment. 
3. All female subjects who are of childbearing potential must be willing to practice highly 
effective contraception (i.e., pregnancy prevention method with a failure rate of <1% per 
year, refer to section 7.1.5 for acceptable methods of contraception) from the time of the 
Baseline visit until 2 weeks after last dose of study drug. 
4. Willing and able (has adequate cognitive ability, in the investigator’s opinion) to comply 
with study visits and study related requirements including providing written informed 
consent. 
 
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4.3 
Exclusion Criteria 
Subjects who meet any of the following criteria are not eligible for participation in the study: 
1. Presence of malignancy within 5 years prior to enrollment (exception for non-melanoma 
cutaneous malignancies). 
2. Presence of a psychiatric diagnosis (such as major depressive disorder, bipolar disorder, 
schizophrenia, psychotic disorder, intellectual disability, severe alcohol abuse disorder) 
meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria in 
past 3 years, history of suicidal ideation within the past 3 years or any history of suicide 
attempt.  
3. Presence of any medical condition or disability, that, in the investigator’s opinion, could 
interfere with the assessment of safety in this study or compromise the safety of the 
subject.  
4. Treatment with any investigational therapy within 4 weeks or 5-half-lives prior to 
enrollment (whichever is longer) or expected participation in another clinical study 
involving an investigational product or device during the subject’s participation in MTI-
107. 
5. Treatment with other neurokinin-1 receptor (NK1-R) antagonists (e.g., aprepitant, 
fosaprepitant, rolapitant) within 4 weeks prior to enrollment. 
6. Treatment with strong cytochrome P450 3A4 inhibitors within 4 weeks prior to 
enrollment (Appendix B). 
7. Currently pregnant or breastfeeding or planning to become pregnant during the study. 
 
5 
STUDY DRUG 
5.1 
Study Drug Supply, Route of Administration, and Storage 
The study drug in this study is serlopitant 5 mg in a film-coated tablet formulation for oral 
administration. The serlopitant tablets contain microcrystalline cellulose, mannitol, 
croscarmellose sodium, silicon dioxide, sodium lauryl sulfate, and magnesium stearate, and 
are film coated with Opadry® Brown.  
The study drug will be provided in bottles that can be stored at room temperature (59-86°F, 
15-30°C). 
Each bottle will each contain 18 serlopitant tablets.  
Additional details regarding study drug supplies can be found in the Pharmacy Manual. 
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5.2 
Labeling and Study Drug Accountability 
The study drug will be appropriately packaged and labeled in bottles with 18 tablets per 
bottle. The study drug supplied for this study is not to be used for any purpose other than this 
study, and study drug accountability must be maintained for all bottles distributed to the 
investigative site. 
Additional details regarding study drug labeling and accountability can be found in the 
Pharmacy Manual. 
5.3 
Dosing Regimen 
During the treatment period, subjects will take one serlopitant 5 mg tablet once daily orally.  
Subjects will be instructed to take all doses from Baseline Visit (Study Day 1) until the Week 
52 Visit, once a day and not within 2 hours before or after a meal. 
Should the study drug be withheld (without intent to discontinue study drug, Section 5.6), the 
drug may be resumed at the discretion of the investigator, at the same dosing regimen.  
5.4 
Dose Modification 
No dose modification of study drug will be allowed during this study.  
5.5 
Missed or Delayed Doses 
Each dose of study drug after the first dose must be administered once daily, and not within 
2 hours before or after a meal. If a dose is missed, that dose will be considered and 
documented as a missed dose.  Dosing should resume as directed the next day. 
5.6 
Study Drug Discontinuation 
Subjects should be discontinued from study drug in the following situations: 
• Any medical condition that may jeopardize the subject’s safety if study drug is continued, 
in the investigator’s and/or Sponsor’s opinion 
• Baseline serum creatinine, total bilirubin, alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) > 2.5 times the upper limit of normal (ULN) (exception may be 
made for retesting within 28 days of enrollment as approved by the Medical Monitor) 
• A female subject becomes pregnant 
• The subject decides to discontinue study drug, or withdraws consent from the study 
• The subject reports use of a strong CYP3A4 inhibitor (as listed in Appendix B) within 4 
weeks of the study visit at which it was reported, initiates any investigational medication, 
or other NK1-R antagonist (exception may be made for use of approved NK1-R 
antagonist for less than 5 continuous days) 
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• Discontinuation is deemed to be in the best interest of the subject, in the investigator’s 
and/or Sponsor’s opinion 
 
The Sponsor or designee should be contacted within 24 hours of investigator’s awareness of 
any study drug discontinuation due to an AE or pregnancy. Investigators should make every 
effort to contact the Sponsor or designee before discontinuing study drug, if possible. 
Subjects who discontinue study drug prior to completing the treatment period will enter a 4-
week follow-up period following the last dose of study drug (Section 6.4.10). Every effort 
should be made for subjects to complete this follow-up visit after a subject has discontinued 
from study drug.  
5.7 
Concomitant and Excluded Therapies 
Concomitant therapies include any therapies (including over-the-counter medications) used 
by a subject from initiation of study drug through the follow-up period. A record of all 
medications used will be maintained for each subject throughout the study. Reported 
information will include a description of the type of drug, treatment period, dosing regimen, 
the route of administration, and drug indication. The use of any concomitant medication must 
relate to the subject’s medical history or to an AE, except for vitamins/nutritional 
supplements and routine preventative immunizations.  
5.7.1 
Excluded Therapies 
The following therapies and activities are excluded from the Baseline visit through the 
follow-up period: 
• NK1-R antagonists (other than study drug, exception may be made for use of approved 
NK1-R antagonist for less than 5 continuous days) 
• Strong CYP3A4 inhibitors (See Appendix B; exceptions may be made for use within 4 
weeks of the study visit at which it was reported) 
• Any investigational drug therapy other than serlopitant 
 
Use of any excluded therapies should be reported as soon as possible, and will be recorded as 
protocol deviations for subjects who receive them. Subjects may be discontinued from the 
study drug (Section 5.6). 
5.8 
Assignment to Treatment  
Eligible subjects will receive serlopitant 5 mg tablets. 
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5.9 
Treatment Compliance 
Records of study drug used, dosages administered, and intervals between visits will be kept 
during the study. Subjects will be asked to return all partially used and empty bottles to the 
study site at each visit. The site staff will count and record the number of remaining tablets in 
each returned bottle. Missed doses will be recorded as reported by the subject. A subject who 
has deviated significantly from the once-daily dosing regimen will be counseled. 
6 
STUDY SCHEDULE AND ASSESSMENTS  
6.1 
Efficacy Parameters 
6.1.1 
Itch Numeric Rating Scale 
The Itch NRS is a validated, self-reported instrument for measurement of itch intensity. WI-
NRS scores will be captured as per Appendix A. Subjects are asked to rate the intensity of 
their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher 
scores indicate greater itch intensity. In this study, WI-NRS during a 24-hour recall period 
prior to the specified visit will be captured.  
6.1.2 
Investigator’s Global Assessment of PN Stage 
The IGA PN-S is an instrument used to assess the overall number and thickness of PN 
lesions at a given time point, as determined by the investigator. It consists of a 5-point scale 
ranging from 0 (clear) to 4 (severe). The IGA PN-S uses clinical characteristics including the 
number of nodules and their thickness, as guidelines for the overall severity assessment. 
IGA PN-S scores will be captured as per Appendix A. Each assessment during the study 
must be done by the principal investigator (PI) or designee. Every effort should be made to 
ensure that all assessments for a given subject are done by the same individual throughout the 
study. However, a change in assessor for a given subject, though not ideal, will not be 
considered a protocol deviation. 
6.1.3 
Patient-Reported Outcomes Measurement Information System Itch 
Questionnaire  
PROMIS-PIQ is an itch-specific instrument that measures quality of life impairment related 
to itch in the previous week. The PROMIS-PIQ includes 4 domains (General, Scratching 
Behavior, Mood and Sleep, and Activity and Clothing). Subjects will complete the PROMIS-
PIQ short forms as per Appendix A.    
6.1.4 
Dermatology Life Quality Index  
DLQI is a dermatology specific quality of life instrument designed to assess the impact of the 
skin disease on a subject’s quality of life over the prior week. It is a ten-item questionnaire 
that assesses overall quality of life (QOL) and six aspects that may affect QOL (symptoms 
and feelings, daily activities, leisure, work or school performance, personal relationships, and 
treatment). The DLQI questionnaire will be collected as per Appendix A. 
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6.1.5 
Photographs 
At selected investigative sites, optional photographs of representative areas with PN 
involvement will be taken at multiple time points, as per Appendix A. These areas may 
include the extensor surfaces of both arms and both legs (overview of both legs, detail of 
lower legs), and the abdomen and back. The central photography vendor will provide 
photographic equipment to the sites for use during the study. Detailed instructions will be 
provided in a Photography Manual. 
6.2 
Safety Parameters 
Safety assessments will consist of monitoring and recording protocol-defined AEs and SAEs; 
vital signs; physical examinations; clinical laboratory assessments; ECGs; and other 
protocol-specified tests that are deemed critical to the safety evaluation of the study drug. 
6.2.1 
Vital Signs 
Vital signs will include measurements of heart rate, blood pressure, respiration rate, and 
temperature after the subject has been calmly resting (seated or supine) for a minimum of 
5 minutes. Vital signs will be assessed as per Appendix A and at unscheduled study visits 
when clinically indicated. When possible, assessment of vital signs should precede blood 
draw.  
6.2.2 
Physical Examination 
Physical examinations will be performed as per Appendix A and at unscheduled study visits 
when clinically indicated. A complete physical examination will be performed at the 
Baseline visit, while subsequent examinations will be abbreviated and targeted to changes in 
disease activity and/or subjects’ symptoms. The subjects’ height and weight will be measured 
as per Appendix A. 
6.2.3 
Clinical Laboratory Assessments 
Samples for clinical laboratory assessments will be collected as per Appendix A and at 
unscheduled study visits when clinically indicated, and analyzed at a central laboratory 
unless otherwise specified. When possible, blood draws should follow ECGs and vital sign 
measurements if they occur on the same visit.  
Detailed instructions regarding sample collection, preparation, and shipment can be found in 
the laboratory manual. Laboratory assessments will include the following: 
• Hematology: hematocrit, hemoglobin, red blood cell count, red blood cell indices, 
platelets, white blood cell count, white blood cell differential (neutrophils, lymphocytes, 
monocytes, basophils, eosinophils) 
• Chemistry: sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, 
creatinine, calcium, phosphorus, magnesium, albumin, uric acid, total protein, alanine 
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aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total 
bilirubin, lactate dehydrogenase (LDH), lipid panel 
• Pregnancy testing: all females of childbearing potential will have a local urine pregnancy 
test performed. Positive or equivocal urine pregnancy test results will be confirmed by a 
serum pregnancy test analyzed at a central laboratory 
• Reproductive endocrinology (for all female subjects under 55 years of age at consent): 
serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, 
progesterone, anti-Mullerian hormone (AMH)  
 
6.2.4 
Electrocardiogram  
A standard 12-lead ECG will be performed after the subject has been calmly resting in a 
supine position for a minimum of 5 minutes before obtaining the ECG. When possible, ECGs 
should precede measurement of vital signs and blood draw for clinical laboratory tests. ECGs 
will be performed as per Appendix A and at unscheduled study visits when clinically 
indicated. ECGs will be reviewed and reported by a central ECG vendor. The ECG machine 
and detailed instructions will be provided by the ECG vendor. 
6.2.5 
Assessment of Potential for Physical Dependence 
NK1-R antagonist dependence has not previously been described and therefore a drug class-
specific, reliable and sensitive instrument for the assessment of withdrawal symptoms has not 
been developed. A surrogate assessment tool, such as those developed for opioid or 
benzodiazepine dependence, is not available. 
In the statistical analysis plan (SAP), the Sponsor will specify a targeted medical event list 
(TEAEs) that may be associated with physical dependence, and evaluate reports of these 
events in the monitored 4-week post-drug discontinuation period.   
6.3 
Subject Flow Diagram 
The visit schedule and assessments are summarized in Appendix A.  
6.4 
Study Visits 
The following sections describe the procedures and assessments to be performed at each 
study visit. Details of each procedure and assessment can be found in Sections 6.1 and 6.2. 
The timing of each study visit is relative to the day of enrollment (Baseline Visit). 
Unscheduled visits may be performed as necessary, and may include procedures or 
assessments deemed necessary by the investigator. 
6.4.1 
Baseline Visit 
The Baseline Visit may coincide with the final visit of the MTI-103, MTI-105, MTI-106, or 
MTI-109 studies. 
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The following procedures are to be performed at the Baseline Visit (Day 1): 
• Obtain written informed consent prior to any protocol-mandated procedures (must be 
obtained prior to any other assessments) 
• Confirm subject’s eligibility based on the inclusion/exclusion   
• Collect demographic information (when permitted by regional laws or guidelines: sex, 
date of birth, race/ethnicity)  
• Collect any concomitant medications 
• Review and record subject’s medical history, including ongoing TEAEs from prior study 
(if applicable) 
• Perform complete physical examination (including height and weight)  
• Obtain ECG  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Draw blood for clinical laboratory tests (exception: participants in MTI-103, MTI-105, 
MTI-106, and MTI-109 who have had these labs in prior 14 days, in the context of that 
study) 
- 
Hematology 
- 
Chemistry 
- 
Reproductive endocrine labs for females under 55 years of age at consent  
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
PROMIS-PIQ 
- 
DLQI 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Register Baseline Visit into the Interactive Web Response System (IWRS)  
• Dispense study drug 
• Confirm next scheduled visit date 
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6.4.2 
Week 4 Visit 
The Week 4 Visit occurs 28 days (±7 days) after the Baseline Visit. At the Week 4 Visit, the 
following procedures and assessments are to be performed:  
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.3 
Week 8 Visit 
The Week 8 Visit occurs 56 days (±7 days) after the Baseline Visit. At the Week 8 Visit, the 
following procedures and assessments are to be performed:  
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
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• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.4 
Week 12 Visit 
The Week 12 Visit occurs 84 days (±7 days) after the Baseline Visit. At the Week 12 Visit, 
the following procedures and assessments are to be performed:  
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.5 
Week 20 Visit 
The Week 20 Visit occurs 140 days (±7 days) after the Baseline Visit. At the Week 20 Visit, 
the following procedures and assessments are to be performed:  
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• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
PROMIS-PIQ 
- 
DLQI 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.6 
Week 28 Visit 
The Week 28 Visit occurs 196 days (±7 days) after the Baseline Visit. At the Week 28 Visit, 
the following procedures and assessments are to be performed:  
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Reproductive endocrine labs for females under 55 years of age at consent  
- 
Hematology 
- 
Chemistry 
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• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.7 
Week 36 Visit 
The Week 36 Visit occurs 252 days (±7 days) after the Baseline Visit. At the Week 36 Visit, 
the following procedures and assessments are to be performed:  
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
PROMIS-PIQ 
- 
DLQI 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
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6.4.8 
Week 44 Visit 
The Week 44 Visit occurs 308 days (±7 days) after the Baseline Visit. At the Week 44 Visit, 
the following procedures and assessments are to be performed:  
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.9 
Week 52 Visit 
The Week 52 Visit occurs 364 days (±7 days) after the Baseline Visit. At the Week 52 Visit, 
the following procedures and assessments are to be performed:  
• Register visit into the IWRS 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Reproductive endocrine labs for females under 55 years of age at consent  
- 
Hematology 
- 
Chemistry 
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• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
PROMIS-PIQ 
- 
DLQI 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug 
• Confirm next scheduled visit date 
 
6.4.10 
Early Treatment Discontinuation Visit/Post-Drug Observation 
The Early Treatment Discontinuation (ETD) Visit occurs within 28 days of last dose for 
subjects who discontinue serlopitant treatment prior to Week 52.  
The Post-Drug Observation Visit occurs 28 days (±7 days) after the Week 52 Visit.  
At the ETD/Post-Drug Observation Visit, the following procedures and assessments are to be 
performed:  
• Register visit into the IWRS 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Perform targeted physical examination with weight 
• Obtain ECG (ETD only) 
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
• Ask subject to complete WI-NRS 
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• Ask the subject to complete the following questionnaires (ETD only): 
- 
PROMIS-PIQ 
- 
DLQI 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography, ETD only) 
• Collect returned study drug (ETD only) 
 
6.4.11 
Early Termination 
Early termination of a subject from the study may occur due to loss to follow-up or 
withdrawal of consent by the subject. In accordance with legal requirements and 
International Conference on Harmonization (ICH) – Good Clinical Practice (GCP) 
guidelines, every subject or his/her legal representative has the right to withdraw from the 
study at any time and without providing reasons. If provided, the reason (adverse event, 
study burden, lack of efficacy, other) a subject withdrew consent will be recorded in the 
electronic Case Report Form (eCRF). Attempts to contact subjects who are suspected of 
being lost to follow-up must be documented in the subject’s source documents. 
7 
ASSESSMENT OF SAFETY 
7.1 
Definitions 
7.1.1 
Adverse Event 
An AE is any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. An AE can be any unfavorable and unintended sign 
(e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a drug, without any judgment about causality. 
AEs include treatment emergent exacerbations of pre-existing illnesses and AEs that occur as 
a result of protocol-mandated interventions. 
7.1.2 
Serious Adverse Event  
An AE is considered “serious” if it results in any of the following outcomes: 
• Death 
• Life-threatening AE (i.e. the subject was at immediate risk of death from the event as it 
occurred. An event that might have led to death if it had occurred with greater severity is 
not “life-threatening”) 
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• Inpatient hospitalization or prolongation of existing hospitalization  
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• Congenital anomaly/ birth defect 
• Important medical event (i.e. an event that may not result in death, be life-threatening, or 
require hospitalization, but which may be considered serious by the investigator or 
Sponsor, as it may jeopardize the subject and may require medical/surgical intervention 
to prevent one of the outcomes listed above). Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, 
blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse. 
 
The following are not considered SAEs: a visit to the emergency room or other hospital 
department < 24 hours that does not result in admission (unless considered an important 
medical or life-threatening event), an elective surgery planned prior to signing consent, 
admission as per protocol for planned medical/surgical procedure, and/or routine health 
assessments requiring admission for baseline/trending of health status (e.g. routine 
colonoscopy). 
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an 
AE (e.g. mild, moderate, or severe pain); the event itself may be of minor medical 
significance (e.g. severe back pain). “Serious” is a regulatory definition, as defined above. 
Seriousness (not severity) serves as the basis for defining regulatory reporting obligations.  
Severity and seriousness should be independently assessed when recording AEs and SAEs on 
the eCRF. 
7.1.3 
Abnormal Physical Exam, Laboratory, Vital Sign, and Electrocardiogram 
Findings  
Abnormal physical exam findings that are clinically significant and are identified prior to the 
first dose of study drug should be recorded as medical history. New or worsening clinically 
significant abnormal physical exam findings identified after the first dose of study drug 
should be recorded as AEs.   
Only abnormal laboratory, vital sign, and ECG findings that are considered clinically 
significant by the investigator (e.g. require active management or are associated with 
accompanying symptoms/signs) will be recorded as medical history or AEs on the eCRF. 
Abnormal laboratory, vital sign, and ECG findings that occur prior to the first dose of study 
drug should be recorded as medical history, and abnormal findings that occur after the first 
dose of study drug should be recorded as AEs. 
If the clinically significant laboratory, vital sign, or ECG abnormality is a sign associated 
with a confirmed disease or condition (e.g. elevated creatinine in a subject diagnosed with 
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chronic kidney disease), only the diagnosis (chronic kidney disease) needs to be recorded on 
the AE eCRF (rather than listing individual test findings as AEs).  
Separate instances of the same clinically significant laboratory, vital sign, or ECG 
abnormality across visits should not be recorded as separate AEs or SAEs. 
7.1.4 
Deaths  
Any deaths that occur from the time of informed consent to the follow-up visit, regardless of 
attribution, must be reported within 24 hours of investigator’s awareness of the death. See 
Safety Form Completion Instructions for complete instructions. 
The Sponsor should be provided a copy of any post-mortem findings and/or relevant medical 
reports, including histopathology. 
7.1.5 
Pregnancies and Contraception Requirements for Females 
For the purposes of this study, a female of childbearing potential is defined as any female 
who has experienced menarche and is pre-menopausal; a post-menopausal state is defined as 
no menses for 12 months without an alternative medical cause in a previously menstruating 
female.  
For the purposes of this study, acceptable contraception is defined below based on 
Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals: ICH M3(R2) dated January 2010, and other available 
guidelines (“U.S. Medical Eligibility Criteria for Contraceptive Use” 2010; 
“Recommendations related to contraception and pregnancy testing in clinical trials” 2014; 
“M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals” 2010):  
All female subjects of childbearing potential must use highly effective contraception, which 
includes the use of one or more of the following acceptable methods:  
1. Surgical sterilization (e.g., bilateral tubal occlusion or ligation, hysterectomy, bilateral 
salpingectomy, bilateral oophorectomy) 
2. Total (as opposed to periodic or cyclic) abstinence from heterosexual intercourse 
3. Hormonal contraception associated with consistent inhibition of ovulation; these may 
include (but are not necessarily limited to) oral, intravaginal, implantable, injectable, or 
transdermal delivery methods.  
a. Progesterone only oral contraceptives are excluded as a highly effective method, as 
they do not consistently inhibit ovulation. 
4. Intrauterine device/system  
5. Exclusive monogamous intercourse with a sterilized (i.e., vasectomized) or otherwise 
non-fertile (e.g., castrated) male partner  
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Any pregnancy occurring in a female subject or the female partner of a male subject, from 
the first study drug administration through the 4-week follow-up visit must be reported 
within 24 hours of the investigator’s awareness of the pregnancy. See Safety Form 
Completion Instructions for complete instructions.  
The investigator will follow the pregnancy to delivery or other pregnancy outcome.  
Pregnancy in a female clinical trial subject or female partner of a male clinical trial subject is 
not an SAE per se. Complications of such pregnancies (for example, spontaneous abortion) 
may qualify as SAEs and should be reported as such even if they occur after the Follow-up 
visit. Any congenital anomalies/birth defects must be recorded and reported as SAEs. See 
Safety Form Completion Instructions for complete instructions.  
7.1.6 
Worsening of Pruritus or Underlying Pruritic Skin Disease 
Pruritus or the underlying pruritic skin disease (PN, AD, or psoriasis) should be recorded as 
an AE or SAE only if considered by the investigator to have worsened in severity beyond the 
subject’s typical fluctuations. It is important to include a description of the nature of the 
unexpected worsening when recording the AE or SAE (e.g. new PN lesions in previously 
uninvolved skin). 
7.2 
Methods and Timing for Recording and Reporting Adverse Events 
7.2.1 
Adverse Event Reporting Period 
Any AE occurrence during the study must be recorded on source documentation and eCRF at 
the site, in accordance with protocol instructions.  
AEs and SAEs will be recorded from the first study drug administration through the follow-
up visit. After the 4-week follow-up visit, only SAEs that are believed to be drug-related 
should be reported. 
After informed consent, but prior to initiation of study drug, only SAEs considered by the 
investigator to be caused by a protocol-mandated intervention will be collected (e.g. SAEs 
related to invasive procedures such as blood collection). These procedure-related SAEs 
should only be reported on the source documents and SAE form, not on the AE eCRF. 
Subjects who undergo Baseline visit procedures but are not enrolled into the study will not 
have SAEs recorded in the clinical database. 
7.2.2 
Eliciting Adverse Events 
Investigators will seek information on AEs and SAEs at each subject contact through the 
follow-up visit. All AEs and SAEs, whether reported by the subject or noted by authorized 
study personnel, will be recorded in the subject’s medical record and on the AE eCRF page, 
and, if serious, on the SAE form. For each AE and SAE recorded, the investigator will make 
an assessment of seriousness, severity, and causality. 
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7.2.3 
Assessment of Severity 
All AEs entered into the eCRF will be graded for severity using the National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 (“Common 
Terminology Criteria for Adverse Events (CTCAE)” 2010) to describe the maximum 
intensity of the adverse event.   
If the AE cannot be found in the event-specific NCI CTCAE grading criteria, the investigator 
should use the definitions for Grade 1, 2, 3, and 4 in Table 1. 
 Table 1 
Adverse Event Grading 
Grade 
Severity 
Alternate Descriptiona 
1 
Mild (apply event-specific NCI 
CTCAE grading criteria) 
Asymptomatic or mild symptoms; clinical or 
diagnostic observations only; intervention not 
indicated. 
2 
Moderate (apply event-specific NCI 
CTCAE grading criteria) 
Minimal, local or noninvasive intervention 
indicated; limiting age-appropriate 
instrumental activities of daily living (ADLb) 
3 
Severe (apply event-specific NCI 
CTCAE grading criteria) 
Severe or medically significant but not 
immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; 
disabling; limiting self care ADLc 
4 
Very severe, life threatening, or 
disabling (apply event-specific NCI 
CTCAE grading criteria) 
Life-threatening consequences; urgent 
intervention indicated. 
5 
Death related to AE 
 
a 
Use these alternative definitions for Grade 1, 2, 3, and 4 events when the observed or reported AE is not in 
the NCI CTCAE listing. A semi-colon indicates ‘or’ within the alternate description of the grade. 
b 
Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
c 
Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden. 
Source: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 
 
Note that severity, a measure of intensity, is not equivalent to seriousness, a regulatory 
definition of outcome. Regardless of severity, some AEs may meet the criteria for 
seriousness. See Section 7.1.2 for the definition of an SAE. 
If an adverse event changes in severity during the same study period (e.g., treatment period), 
only the highest severity grade will be recorded on the eCRF.  
7.2.4 
Assessment of Causality 
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious). An investigator’s causality assessment is the determination of whether there exists a 
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reasonable possibility that the investigational product caused or contributed to an AE. 
Causality of an AE will be assessed by the investigator using the following terms: 
• Likely Related: A reaction that follows a reasonable temporal sequence from 
administration of the study drug; that follows a known or expected response pattern to the 
suspected study drug; and for which other potential etiologies are considered less likely 
factors than the study drug. 
• Likely Unrelated: A reaction that, considering all potential etiologies, is most likely due 
to factors other than the study drug. 
 
7.3 
Follow-up of Adverse Events and Serious Adverse Events 
The investigator must make every effort to follow all AEs and SAEs regardless of attribution 
until judged resolved or stabilized, the subject is lost to follow-up, or it has been determined 
that treatment with study drug or participation in the study is not the cause of the AE or SAE. 
7.4 
Reporting Serious Adverse Events to the Sponsor and Institutional 
Review Board (IRB) or Ethics Committee (EC)  
The Sponsor or designee is under obligation to report certain SAEs to regulatory authorities 
related to investigational drugs in clinical trials. The Sponsor or designee must be notified 
within 24 hours of an AE when the investigator determines that an AE meets the protocol 
definition of an SAE, regardless of the cause or relationship to study drug.  
An SAE related to study participation occurring before study drug administration and after 
informed consent should be promptly reported to the Sponsor. If the investigator learns of 
any SAE at any time after a participant has been discharged from the study, and the SAE is 
considered likely related to study drug, the SAE should be promptly reported to the Sponsor. 
Please see the Safety Form Report Completion Instructions for safety reporting instructions.  
The investigator must also comply with applicable requirements concerning reporting of 
SAEs to the IRB or EC. This may include initial or follow-up notification of an SAE or other 
safety information. 
7.5 
Reporting Serious Adverse Events to Regulatory Authorities and Study 
Investigators 
The Sponsor, or its designee, is responsible for submitting reports of serious, unexpected 
related adverse events to regulatory authorities on an expedited basis, according to the ICH 
E2A Guideline and to other regulatory authorities according to national and local regulations 
as required. The Sponsor, or its designee, is responsible for prompt submission to the IRB or 
EC of any expedited SAE reports submitted to regulatory authorities. All investigators 
participating in ongoing clinical studies with serlopitant will receive copies of the SAE 
reports submitted on an expedited basis to regulatory authorities. 
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8 
STATISTICAL METHODS  
All statistical processing will be performed using SAS® unless otherwise stated. No interim 
analyses are planned. Data will be summarized with descriptive statistics by visit. For 
continuous variables, the following information will be presented: n, mean, standard 
deviation, median, minimum and maximum. For categorical variables, counts and 
percentages will be used. 
Baseline will be the last recorded value prior to the start of treatment.  
A SAP describing all statistical analyses will be written as a separate document. 
8.1 
Handling of Missing Data and Excluded Therapy Use  
Summary statistics will generally be reported based upon observed data. Should a 
determination of treatment period (on treatment, pre-treatment) be required for adverse 
events or concomitant medication but the corresponding date is missing, or is a partial date, 
the event/medication will be considered on treatment unless the portions of the date that are 
available indicate this is not possible. 
8.2 
Analysis Population  
All subjects who receive at least 1 confirmed dose of study drug and have at least 1 post-
baseline safety assessment will be included in the safety population. All analyses will be 
performed using the safety population.   
8.3 
Subject Disposition  
An accounting of all subjects by disposition will be presented. Subjects who discontinue 
study drug prematurely or withdraw from the study will be summarized and listed, with a 
description of the reason for early termination/withdrawal. 
8.4 
Subject Characteristics  
Demographic and other baseline characteristics will be summarized. 
8.5 
Concomitant Medications  
Concomitant medications will be coded by the World Health Organization Drug Dictionary 
to Anatomical Therapeutic Classification (ATC) and preferred drug name. Concomitant 
medications will be summarized by ATC level and preferred drug name and listed. 
8.6 
Treatment Compliance and Extent of Exposure  
Compliance with study drug dosing will be determined based on tablet counts recorded on 
the eCRF. Compliance will be calculated by analyzing expected number of tablets returned 
versus actual number of tablets returned. Summaries of treatment exposure will also be 
produced.  
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8.7 
Efficacy Analyses  
Descriptive statistics will be used to summarize the following: 
• Changes from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52  
• Changes from baseline in PROMIS-PIQ score for Itch (General, Scratching Behavior, 
Mood and Sleep, Activity and Clothing) to Weeks 20, 36, and 52 
• Changes from baseline in DLQI (symptoms and feelings, daily activities, leisure, work or 
school performance, personal relationships, and treatment) to Weeks 20, 36 and 52 
• Changes from baseline in IGA PN-S to Weeks 4, 8, 20, 28, 36, 44, and 52.   
 
Data will be summarized by time point using frequency tabulations or descriptive statistics as 
appropriate. Observed results, as well as change from baseline will be summarized, as 
appropriate. 
8.8 
Safety Analyses  
8.8.1 
Adverse Events  
All AEs will be classified by system organ class and preferred term using the Medical 
Dictionary for Regulatory Activities (MedDRA). TEAEs will be tabulated in a manner which 
provides information about the incidence of TEAEs for the entire treatment period as well as 
by time period in order to understand the evolution of TEAEs over time. Thus, in addition to 
the TEAE analysis over the entire 12-month treatment time, results will be presented for the 
following periods: 0 to 4 weeks, > 4 to 12 weeks, > 12 to 28 weeks, > 28 weeks to 36 weeks, 
> 36 to end of treatment, and end of treatment to end of the study. Additionally, the pre-
specified TEAEs and SAEs that may be associated with physical dependence will be 
summarized separately. For incidence reporting, if a subject reported more than one TEAE 
that was coded to the same system organ class or preferred term, the subject will be counted 
only once for that specific system organ class or preferred term. An overview of AEs, which 
includes subject incidence of AEs, TEAEs, treatment-related TEAEs, TEAEs by severity, 
SAEs, deaths, and AEs leading to discontinuation, will be presented.  
All information pertaining to AEs noted during the study will be listed by subject and will 
include a verbatim description of the event as reported by the investigator, as well as the 
preferred term, system organ class, start date, end date (if ended), seriousness, severity, 
action taken regarding the study drug, outcome, and relationship to the study drug. In 
addition, a listing of subjects who prematurely discontinue from the study due to AEs will be 
provided. 
SAEs will be listed and summarized in a similar manner to AEs. 
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8.8.2 
Clinical Safety Laboratory Results  
Clinical safety laboratory values will be measured by a central laboratory. Summary statistics 
for actual values and for changes from baseline will be tabulated for laboratory results by 
scheduled visit. Graphs of laboratory values over time will also be produced, and listings will 
be provided.  
Subjects with clinical laboratory values outside of the normal reference range at any post-
baseline assessment will be summarized. Shifts from baseline laboratory values will be 
tabulated. A listing of all out-of-range laboratory test results, including assessment of clinical 
significance, will also be provided. 
8.8.3 
Vital Signs  
The observed vital sign data and change from baseline for each scheduled visit will be 
summarized with descriptive statistics, and presented in a listing.  
8.8.4 
Electrocardiograms  
The overall ECG assessment (abnormal or normal) and parameters will be summarized along 
with a summary of how many subjects developed a post-treatment abnormal result, and will 
be presented in a listing. 
8.8.5 
Physical Exams  
Physical exam findings will be recorded by the sites within medical history or adverse events 
and otherwise not summarized, with the exception of weight and change from baseline in 
weight. 
9 
ADMINISTRATIVE ASPECTS 
9.1 
Changes to the Protocol 
Protocol amendments must be made only with the prior written approval of the Sponsor. An 
investigator signature will be obtained for the initial protocol and any amendments. 
Substantial amendments will be provided to the appropriate regulatory authorities. No 
protocol changes affecting the following will be made without the written approval of the 
Sponsor and the responsible IRB or EC: 
• Safety and/or eligibility of subjects 
• Data integrity 
• Study design or conduct 
• Willingness of a subject to participate in the study 
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9.2 
Study Termination 
The Sponsor has the right to terminate this study at any time. Reasons may include, but are 
not limited to, evidence of a potential safety risk in this study or other serlopitant studies or 
poor enrollment. A written statement fully documenting the reasons for study termination 
will be provided to the IRB or EC. 
9.3 
Monitoring and Auditing Procedures 
The Sponsor will designate study monitors who will be responsible for monitoring the 
conduct of this study. A separate study Monitoring Plan will include details regarding the 
responsibilities of the study monitors, investigator responsibilities in providing access to 
records and addressing issues identified, the frequency and structure of monitoring visits, and 
adherence to subject confidentiality as outlined in the Informed Consent Form (ICF). 
9.4 
Transfer of Obligations 
The Sponsor will delegate certain aspects of study oversight to Contract Research 
Organizations (CROs). The specific responsibilities will be detailed in Transfer of 
Obligations documents.  
9.5 
Informed Consent 
The purpose of the study, the procedures to be carried out, and any potential risks of study 
participation will be described in non-technical terms in the ICF. After having reviewed and 
understood the ICF, subjects will be required to read, sign, and date an IRB-approved or EC-
approved consent form before any study-specific procedures are carried out. Subjects will be 
assured that they may withdraw from the study at any time without jeopardizing medical care 
related to or required as a result of study participation. The original signed consent form will 
be maintained in the investigator site file. Copies of signed consent forms will be provided to 
the subject. 
9.6 
Communication with the Institutional Review Board or Ethics Committee 
The IRB or EC is constituted and operates in accordance with the principles and 
requirements described in the ICH E6(R2) guideline. The protocol, ICF, other written subject 
information, and any proposed study advertising material must be submitted to the IRB or 
EC for written approval. IRB or EC approval of these documents will be provided to the 
investigator. The study will not start until the IRB or EC has granted its approval of the study 
materials and procedures. 
Protocol amendments will be submitted to the IRB or EC as explained in Section 9.1. SAE 
information will be submitted to the IRB or EC as explained in Section 7.4.  
If the study is terminated by the Sponsor, a written statement fully documenting the reason(s) 
for study termination will be provided to the IRB or EC. 
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9.7 
Disclosure and Confidentiality 
By signing this protocol, the investigator agrees to keep all information provided by the 
Sponsor in strict confidence and to require the same confidentiality from site staff and the 
IRB or EC. Study documents provided by the Sponsor (e.g. protocol, Investigator Brochure, 
eCRFs) will be stored appropriately to ensure their confidentiality. The information provided 
by the Sponsor to the investigator may not be disclosed to others without direct written 
authorization from the Sponsor, except to the extent necessary to obtain informed consent 
from subjects who wish to participate in the study.  
The investigator must ensure that the subjects be identified by a unique subject study 
number. Other study-related documents that may contain confidential participant information 
(e.g. signed ICFs) will be kept in strict confidence by the investigator and be stored in a 
secure location with access restricted to the study staff. 
9.8 
Records and Electronic Case Report Forms 
All study data except central laboratory and ECG data will be recorded in an eCRF system. 
Data will be entered at the site by the appropriately designated and trained site personnel. All 
source documents from which eCRF entries are derived should be placed in the subject’s 
medical records. eCRFs will be completed for every subject screened in the study. The 
investigator/institution should maintain adequate and accurate source documents and trial 
records that include all pertinent observations on each of the site’s trial subjects. Source data 
should 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 (e.g., via an audit trail). 
The study monitor will review all eCRFs in detail and will have access to participant medical 
records, laboratory data, and other source documentation to allow required eCRF fields to be 
verified by source data. 
Data consistency and plausibility checks against data entered into the eCRF will be included 
in the eCRF system. Data corrections can be performed in the eCRFs by the site. For each 
instance of data modification, the system requires a reason for change. The system keeps a 
full audit trail of the data values, the date and time of modification, and the electronic 
signature of the user who performed the change. 
After a full review of the eCRFs by the study monitor and resolution of any data 
clarifications, the investigator will review, sign, and approve the subject’s eCRF. All 
essential documents, source data, clinical records, and laboratory data will be retained by the 
site in accordance with the ICH E6(R2) guideline and the site’s data retention policies. These 
records must be available for inspection by the Sponsor, monitor, and regulatory authorities. 
Furthermore, the investigators/institutions will permit trial-related monitoring, audits, EC 
review, and inspections by a competent authority as necessary and provide direct access to 
source data/documents. 
Further detail regarding data management and eCRFs is included in the Data Management 
Plan. 
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9.9 
Good Clinical Practice and Ethical Study Conduct 
The study procedures outlined in this protocol will be conducted in accordance with 
applicable ICH Guidelines, including ICH E6(R2): Good Clinical Practice. As this study is 
conducted under a US IND, the investigator will also ensure that the basic principles of 
“Good Clinical Practice”, as outlined in 21 CFR 312, subpart D, “Responsibilities of 
Sponsors and Investigators”, 21 CFR, part 50 and 21 CFR, part 56 are adhered to. 
The study procedures outlined in this protocol will also be conducted in accordance with the 
principles of the Declaration of Helsinki. 
9.10 
End of Study Notification 
The Sponsor will notify appropriate regulatory authorities and the IRB or EC within 90 days 
from the end of the clinical study. The end of the clinical study is defined as the last study 
visit for the last subject. 
9.11 
Publication of Results 
All publications (e.g. manuscripts, abstracts, oral/slide presentations, book chapters) based on 
this study or relying on data from this study must be submitted to the Sponsor for review and 
release before submission for publication. The Sponsor is responsible for final approval of all 
publications. 
9.12 
Final Report 
A clinical trial summary report will be provided to the appropriate regulatory authorities 
within one year of the end of the clinical study. 
 
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10 
REFERENCES  
Akiyama T, Nguyen T, Curtis E, et al. A central role for spinal dorsal horn neurons that 
express neurokinin-1 receptors in chronic itch. Pain. 2015;156(7):1240-6. 
Andoh T NT, Satoh M, Kuraishi Y. Substance P induction of itch-associated response 
mediated by cutaneous NK1 tachykinin receptors in mice. J Pharmacol Exp Ther. 
1998;286(3):1140-1145. 
Booken N, Heck M, Nicolay JP, et al. Oral aprepitant in the therapy of refractory pruritus in 
erythrodermic cutaneous T-cell lymphoma. Br J Dermatol. 2011;164(3):665-67. 
Carstens EE, Akiyama T. Central mechanisms of itch. Curr Probl Dermatol. 2016;50:11-17. 
Chuquilin M, Yazan Alghalith, Fernandez KH. Neurocutaneous disease: Cutaneous 
neuroanatomy and mechanisms of itch and pain. J Am Acad Dermatol. 
2016;74:197-212.  
Common Terminology Criteria for Adverse Events (CTCAE). 4.03 ed: National Institutes of 
Health; 2010. 
Duval A, Dubertret L. Aprepitant as an antipruritic agent? N Eng J Med. 
2009;361:1415-1416. 
El-Nour H, Lundeberg L, Al-Tawil R, et al. Upregulation of the axonal growth and the 
expression of substance P and its NK1 receptor in human allergic contact dermatitis. 
Immunopharmacol Immunotoxicol. 2006;28(4):621-631. 
Emend® (aprepitant) capsule for oral use. U.S. Prescribing Information. Merck Sharp and 
Dohme Corp. Revised August 2015. 
Examples of clinical inhibitors for P450-mediated metabolisms (for concomitant use clinical 
DDI studies and/or drug labeling) (9/26/2016). U.S. Food and Drug Administration; 
2016. 
Gerber PA, Buhren BA, Cevikbas F, et al. Preliminary evidence for a role of mast cells in 
epidermal growth factor receptor inhibitor-induced pruritus. J Am Acad Dermatol. 
2010;63(1):163-165. 
Harrison S GP. Substance P. Int J Biochem. 2001;33(6):555-576. 
Hökfelt T PB, Wahren J. Substance P: A pioneer amongst neuropeptides. J Intern Med 2001; 
249:27–40. 
Ikoma A, Steinhoff M, Ständer S, et al. The neurobiology of itch. Nat Rev Neurosci. 
2006;7:535-547. 
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Lotts T, Ständer S. Research in practice: substance P antagonism in chronic pruritus. J Dtsch 
Dermatol Ges. 2014;12(7):557-559. 
Luo J, Feng J, Liu S, et al. Molecular and cellular mechanisms that initiate pain and itch. Cell 
Mol Life Sci 2015;72:3201-23. 
M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals. Food and Drug Administration; 2010. 
Recommendations related to contraception and pregnancy testing in clinical trials. Clinical 
Trial Facilitation Group; 2014. 
Santini D, Vincenzi B, Guida FM, et al. Aprepitant for management of severe pruritus related 
to biological cancer treatments: a pilot study. Lancet Oncol. 2012;13(10):1020-1024. 
Schmelz M. Itch and pain differences and commonalities. In: Schaible HG. (eds) Pain 
Control. Handbook of Experimental Pharmacology, 2015;227:285-301.   
Ständer S, Siepmann D, Herrgott I, et al. Targeting the neurokinin receptor 1 with aprepitant: 
a novel antipruritic strategy. Plos One. 2010;5(6):e10968.   
Ständer S, Weisshaar E, Raap U. Emerging drugs for the treatment of pruritus. Exp Opin 
Emerg Drugs. 2015;20:515-21. 
Steinhoff M, Bienenstock J, Schmelz M, et al. Neurophysiological, neuroimmunological, and 
neuroendocrine basis of pruritus. J Invest Dermatol. 2006;126:1705-18. 
Steinhoff MS, von Mentzer B, Geppetti P, et al. Tachykinins and their receptors: 
contributions to physiological control and the mechanisms of disease. Physiol Rev. 
2014;94(1):265-301. 
Torres T, Fernandes I, Selores M, et al. Aprepitant: Evidence of its effectiveness in patients 
with refractory pruritus continues. J Am Acad Dermatol. 2012;66(1):e14-15. 
U.S. Medical Eligibility Criteria for Contraceptive Use, 2010. Vol 20172010. 
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APPENDIX A  
SCHEDULE OF ACTIVITIES AND ASSESSMENTS 
Examination 
Baseline1 
Week 4 
(±7 
days) 
Week 8 
(±7 
days) 
 Week 
12 (±7 
days) 
Week 20 
(±7 
days) 
Week 28 
(±7 
days) 
 Week 
36 (±7 
days) 
Week 44 
(±7 
days) 
Week 52 
(±7 
days) 
Early 
Treatment 
Discontinuation 
Post-drug 
observation2 
Informed consent 
X 
  
  
  
  
  
  
  
  
 
  
I/E criteria 
X 
  
  
  
  
  
  
  
  
 
  
Demographics/ 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Physical exam3 
X4 
X 
X 
X 
X 
X 
X 
X 
X 
X4 
X4 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Labs5 
X1 
X 
  
X 
  
X 
  
  
X 
X 
X 
Urine pregnancy test6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
X 
  
  
X 
  
X 
  
X 
X 
 
WI-NRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IGA PN-S (PN 
subjects only) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PROMIS-PIQ and 
DLQI 
X 
  
  
  
X 
  
X 
  
X 
X 
 
Photographs (if 
applicable) 
X 
  
  
  
X 
  
X 
  
X 
X 
 
Dispense and/or collect 
serlopitant 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Review study drug 
compliance  
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs/SAEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1 
Baseline may coincide with the final visit of prior applicable study; Baseline labs do not need to be repeated if completed within prior 14 days 
2 
The post-drug observation visit occurs 28 days (± 7 days) after the Week 52 visit  
3 
Baseline physical exam is complete; all other physical exams are targeted 
4 
Height/weight at Baseline and weight at ETD/post-drug  
5 
Hematology and Chemistry at Baseline, Weeks 4, 12, 28, 52 and ETD/post/drug; Reproductive Endocrinology at Baseline, Weeks 28 and 52 (females 
under 55 years of age at consent) 
6 
For females of childbearing potential (with positive or equivocal results to be confirmed by a serum pregnancy test) 
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APPENDIX B  
LIST OF STRONG CYP3A4 INHIBITORS   
The list of strong CYP3A4 inhibitors is based on the United States Food and Drug 
Administration (FDA) list effective September 26, 2016, Examples of clinical inhibitors for 
P450-mediated metabolisms (for concomitant use clinical DDI studies and/or drug labeling 
(“Examples of clinical inhibitors for P450-mediated metabolisms (for concomitant use clinical 
DDI studies and/or drug labeling (9/26/2016)”).  
Note: This Appendix may be replaced if applicable (e.g., if updated by the FDA) through site 
communications without requiring a protocol amendment. 
1. 
boceprevir 
2. 
clarithromycin 
3. 
cobicistat 
4. 
conivaptan 
5. 
danoprevir and ritonavir 
6. 
diltiazem 
7. 
elvitegravir and ritonavir 
8. 
regular grapefruit juice consumption 
9. 
idelalisib 
10. 
indinavir and ritonavir 
11. 
itraconazolea 
12. 
ketoconazolea 
13. 
lopinavir and ritonavir 
14. 
nefazodone 
15. 
nelfinavir 
16. 
paritaprevir and ritonavir and (ombitasvir and/or dasabuvir) 
17. 
posaconazolea 
18. 
ritonavir 
19. 
saquinavir and ritonavir 
20. 
telaprevir 
21. 
tipranavir and ritonavir 
22. 
troleandomycin 
23. 
voriconazolea 
a 
When administered topically, it may not be considered a strong CYP3A4 inhibitor due to limited systemic 
absorption 
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Menlo Therapeutics Inc. 
MTI-107 Protocol, Summary of Changes Version 1.0 to Version 1.1 
 
 
 
 
1 
CLINICAL STUDY PROTOCOL MTI-107 
SUMMARY OF CHANGES 
 
Drug Product Name: 
Serlopitant  
 
Study Title:  
MTI-107: AN OPEN-LABEL LONG-TERM SAFETY 
STUDY OF SERLOPITANT FOR THE TREATMENT OF 
PRURITUS 
 
Version: 
 
 
1.1 
Release Date:  
 
11 April 2018 
Replaces Previous Version: 1.0 (Dated 18 December 2017) 
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Serlopitant  
 
Menlo Therapeutics Inc. 
MTI-107 Protocol, Summary of Changes Version 1.0 to Version 1.1 
 
 
 
 
2 
OVERVIEW: 
MTI-107 protocol was amended to include language regarding the potential benefit and potential risk for the participating patients 
as well as the assessment of the ratio of this benefit and risk based on receipt of BfArM Deficiency Letter dated 20 March 2018. 
KEY CHANGES: N/A 
ADMINISTRATIVE CHANGES: 
Section(s) 
Summary of Change 
1.2.3 Serlopitant in Pruritus-Related 
Studies 
Amended to include language regarding the potential benefit and potential risk for the 
participating patients as well as the assessment of the ratio of this benefit and risk 
Throughout   
Updated protocol version in the footer 
 
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Page 1 
 
CLINICAL STUDY PROTOCOL 
 
TITLE:  
AN OPEN-LABEL LONG-TERM SAFETY STUDY OF 
SERLOPITANT FOR THE TREATMENT OF PRURITUS  
IND No.: 
 
 
117780 
EudraCT: 
 
 
2017-004211-40 
ClinicalTrials.gov ID:  
NCT03540160 
Protocol No.:  
 
MTI-107 
Protocol Version/Date: 
Version 2.0/03 July 2018 
Development Phase:  
Phase 3 
Sponsor: 
 
 
Menlo Therapeutics Inc. 
200 Cardinal Way, 2nd Floor 
Redwood City, CA 94063, USA 
 
 
 
Confidentiality Statement: 
This document is a confidential communication of Menlo Therapeutics Inc. As such, the 
recipients agree not to disclose or reproduce, without prior written approval, this 
document and any attachments, except to appropriate Institutional Review Boards, Ethics 
Committees, representatives of the US Food and Drug Administration, the European 
Medicines Agency, other Competent Authorities or regulatory agencies, or as otherwise 
required by applicable laws or regulations. 
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Page 2 
 
SIGNATURE PAGE FOR INVESTIGATOR(S) 
 
TITLE:  
AN OPEN-LABEL LONG-TERM SAFETY STUDY OF 
SERLOPITANT FOR THE TREATMENT OF PRURITUS 
IND No.: 
 
 
117780 
EudraCT: 
 
 
2017-004211-40 
ClinicalTrials.gov ID:  
NCT03540160 
Protocol No.:  
 
MTI-107 
Protocol Version/Date: 
Version 2.0/03 July 2018   
Development Phase:  
Phase 3 
Sponsor: 
 
 
Menlo Therapeutics Inc. 
200 Cardinal Way, 2nd Floor 
Redwood City, CA 94063, USA 
 
 
I have read the protocol and agree to conduct this study in accordance with the protocol, all 
relevant laws and regulations in force at the time, International Conference on Harmonisation 
Guidelines for Good Clinical Practice, and the Declaration of Helsinki.  
 
 
 
Principal Investigator’s printed name 
 
 
 
 
 
 
Principal Investigator’s signature 
 
Date (DD-MMM-YYYY) 
 
  
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Page 4 
 
PROTOCOL SYNOPSIS 
Study Title: 
An Open-Label Long-Term Safety Study of Serlopitant for the Treatment of Pruritus  
Protocol Number: 
MTI-107 
Sponsor: 
Menlo Therapeutics Inc. 
Development Phase: 
Phase 3 
Study Objectives: 
Primary objective:  
• 
To assess the long-term safety of serlopitant in adults with pruritus 
associated with prurigo nodularis (PN), atopic dermatitis (AD), or psoriasis. 
Secondary objectives:  
• 
To assess change in severity of pruritus in subjects with PN, AD, or 
psoriasis using the worst-itch numeric rating scale (WI-NRS).  
• 
To assess change in severity and extent of PN using the Investigator’s 
Global Assessment of PN Stage (IGA PN-S), for those subjects with PN. 
• 
To assess whether serlopitant produces physical dependence.  
Study Design: 
Study MTI-107 is a multicenter, open-label study to assess the long-term safety of 
serlopitant in adults with pruritus associated with PN, AD, or psoriasis. Eligible 
subjects who have completed selected studies of serlopitant may be given the 
opportunity, at the investigator’s discretion, to consent to and participate in this 
open-label study, regardless of their treatment allocation in prior studies. If deemed 
necessary by Menlo Therapeutics to meet enrollment objectives, eligible subjects 
who have not participated in a prior serlopitant study may also be enrolled in study 
MTI-107. 
The study will consist of two periods, for a total study period of approximately 
57 weeks: 
• 
Treatment period: 52 weeks 
• 
Post-drug observation period: 5 weeks 
During the treatment period, subjects will take one serlopitant 5 mg tablet once daily 
orally.  
Standard therapy for the concurrent skin lesions and pruritus may be employed 
during this study.  
After completion of the 52-week treatment period, all subjects will enter a 5-week 
post-drug observation period. Subjects who discontinue treatment early will have 
post-drug observation visits through 5 weeks after their last dose of serlopitant.  
Safety Review: 
An internal safety monitoring team consisting of representatives from Menlo 
Therapeutics Inc. and its designees will monitor safety data on a regular basis 
throughout the study. 
Planned Sample Size: 
Approximately 400 subjects  
Study Population: 
The study will enroll adults with pruritus associated with PN, AD, or psoriasis. 
Inclusion Criteria (Subjects must meet the following criteria to be enrolled into the 
study):  
1. Male or female, age 18 years or older at consent. 
2. Subject reports pruritus in the 24-hour period prior to enrollment and: 
a. 
Has completed a prior applicable clinical study of serlopitant 
without a serious adverse event (SAE) that was assessed as likely 
related to the study drug. (For participants from study TCP-102, 
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the WI-NRS score must be ≥ 7 in the 24-hour period prior to the 
Baseline visit.) 
OR  
b. Has not participated in a prior clinical study of serlopitant and has 
a clinical diagnosis of PN, AD, or psoriasis, and has a WI-NRS 
score ≥ 7 in the 24-hour period prior to the Baseline visit, and 
Sponsor has approved enrollment. 
3. All female subjects who are of childbearing potential must be willing to 
practice highly effective contraception (i.e., pregnancy prevention method 
with a failure rate of <1% per year) from the time of the Baseline visit until 
5 weeks after last dose of study drug. 
4. Willing and able (has adequate cognitive ability, in the investigator’s 
opinion) to comply with study visits and study related requirements 
including providing written informed consent. 
 
Exclusion Criteria (Subjects who meet any of the following criteria are not eligible 
for participation in the study): 
1. Presence of malignancy within 5 years prior to enrollment (exception for 
non-melanoma cutaneous malignancies). 
2. Any known major psychiatric diagnosis, such as major depressive disorder, 
bipolar disorder, schizophrenia, psychotic disorder, intellectual disability, 
severe alcohol use disorder, which may confound the assessment of 
serlopitant safety or efficacy, or interfere with the subject’s ability to 
comply with protocol-mandated activities, within 3 years prior to 
enrollment.   
3. Untreated or inadequately treated thyroid, adrenal, or pituitary nodules or 
disease, or history of thyroid malignancy; or the presence of any medical 
condition or disability, that, in the investigator’s opinion, could interfere 
with the assessment of safety in this study or compromise the safety of the 
subject.  
4. Treatment with any investigational therapy within 4 weeks or 5-half-lives 
prior to enrollment (whichever is longer) or expected participation in 
another clinical study involving an investigational product or device during 
the subject’s participation in MTI-107. 
5. Treatment with other neurokinin-1 receptor (NK1-R) antagonists (e.g., 
aprepitant, fosaprepitant, rolapitant) within 4 weeks prior to enrollment. 
6. Treatment with strong cytochrome P450 3A4 inhibitors within 4 weeks 
prior to enrollment. 
7. Currently pregnant or breastfeeding or planning to become pregnant during 
the study. 
Study Drug: 
Serlopitant 5 mg tablets 
Dosage:  
Serlopitant: 5 mg once daily orally for 52 weeks  
Safety Endpoints: 
• 
Incidence of treatment-emergent adverse events (TEAEs) and SAEs 
• 
Change from baseline in clinical laboratory parameters following study 
drug exposure 
• 
Change from baseline in vital sign and electrocardiogram (ECG) 
parameters following study drug exposure 
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• 
Change from baseline in the Hospital Anxiety and Depression Scale 
(HADS)  
• 
Change from baseline in the Epworth Sleepiness Scale (ESS) 
• 
Assessment of physical dependence following chronic study drug exposure, 
in the monitored 5-week post-drug discontinuation period  
Efficacy Endpoints: 
• 
Change from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52  
• 
Change from baseline in Dermatology Life Quality Index (DLQI) 
(symptoms and feelings, daily activities, leisure, work or school 
performance, personal relationships, and treatment) to Weeks 20, 36 and 52 
• 
Change from baseline in IGA PN-S to Weeks 4, 8, 20, 28, 36, 44, and 52 
Statistical Methods: 
All subjects who receive at least 1 confirmed dose of study drug and have at least 1 
post-baseline safety assessment will be included in the safety population. All 
analyses will be performed using the safety population. 
Data will be summarized with descriptive statistics by visit. For continuous 
variables, the following information will be presented: n, mean, standard deviation, 
median, minimum and maximum. For categorical variables, counts and percentages 
will be used. 
All adverse events (AEs) will be classified by system organ class and preferred term 
using the Medical Dictionary for Regulatory Activities (MedDRA). TEAEs will be 
tabulated in a manner which provides information about the incidence of TEAEs for 
the entire treatment period as well as by specified time periods in order to 
understand the evolution of TEAEs over time. An overview of AEs, which includes 
subject incidence of TEAEs, treatment-related TEAEs, TEAEs by severity, SAEs, 
deaths, and AEs leading to discontinuation, will be presented.  
Summary statistics for actual safety laboratory values and for changes from baseline 
will be tabulated by scheduled visit. Subjects with clinical laboratory values outside 
of the normal reference range at any post-baseline assessment will be summarized. 
Shifts from baseline laboratory values will be tabulated. A listing of all out-of-range 
laboratory test results, including assessment of clinical significance will also be 
provided. 
The observed vital sign data and change from baseline will be summarized with 
descriptive statistics and presented in a listing. 
The overall ECG assessment (abnormal or normal) will be summarized and 
descriptively characterized, along with a summary of how many subjects developed 
a post treatment abnormal result.  
Physical exam findings will be recorded by the sites within medical history or AEs 
and otherwise not summarized, with the exception of weight, and change from 
baseline in weight. 
The WI-NRS, DLQI, and IGA PN-S will be summarized with descriptive statistics 
by visit. 
Summary statistics for the HADS and ESS actual values and change from baseline 
will be presented by scheduled visit. 
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Study Sites: 
Approximately 120 study sites 
Expected Duration of 
Subject’s 
Participation 
Approximately 57 weeks: 52 weeks of treatment, and a post-drug observation period 
of 5 weeks. 
 
This study will be conducted in accordance with the Guidelines of Good Clinical Practice. 
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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ............................................................................................1 
SIGNATURE PAGE FOR INVESTIGATOR(S) .....................................................................2 
SPONSOR PROTOCOL APPROVAL SIGNATURE(S) .........................................................3 
PROTOCOL SYNOPSIS ..........................................................................................................4 
TABLE OF CONTENTS ...........................................................................................................8 
LIST OF APPENDICES ..........................................................................................................11 
LIST OF TABLES ...................................................................................................................11 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..........................................12 
1 
INTRODUCTION .................................................................................................13 
1.1 
Pruritus .............................................................................................................13 
1.1.1 
Role of Substance P and the Neurokinin-1 Receptor in Pruritus .........13 
1.2 
Serlopitant ........................................................................................................14 
1.2.1 
Serlopitant Background and Nonclinical Summary ............................14 
1.2.2 
Serlopitant Clinical Summary ..............................................................15 
1.2.3 
Serlopitant in Pruritus-Related Studies ................................................15 
2 
STUDY OBJECTIVES ..........................................................................................17 
3 
STUDY DESIGN...................................................................................................17 
3.1 
Overall Study Design .......................................................................................17 
3.2 
Rationale for Study Design and Dose Selection ..............................................18 
3.3 
Study Endpoints ...............................................................................................18 
3.3.1 
Safety Endpoints ..................................................................................18 
3.3.2 
Efficacy Endpoints ...............................................................................18 
3.4 
Safety Review ..................................................................................................19 
3.4.1 
Safety Monitoring Team ......................................................................19 
4 
SELECTION OF STUDY POPULATION ...........................................................19 
4.1 
Study Population ..............................................................................................19 
4.2 
Inclusion Criteria .............................................................................................19 
4.3 
Exclusion Criteria ............................................................................................20 
5 
STUDY DRUG ......................................................................................................20 
5.1 
Study Drug Supply, Route of Administration, and Storage.............................20 
5.2 
Labeling and Study Drug Accountability ........................................................21 
5.3 
Dosing Regimen...............................................................................................21 
5.4 
Dose Modification ...........................................................................................21 
5.5 
Missed or Delayed Doses.................................................................................21 
5.6 
Study Drug Discontinuation ............................................................................21 
5.7 
Concomitant and Excluded Therapies .............................................................22 
5.7.1 
Excluded Therapies ..............................................................................22 
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5.8 
Assignment to Treatment .................................................................................23 
5.9 
Treatment Compliance .....................................................................................23 
6 
STUDY SCHEDULE AND ASSESSMENTS ......................................................23 
6.1 
Efficacy Parameters .........................................................................................23 
6.1.1 
Itch Numeric Rating Scale ...................................................................23 
6.1.2 
Investigator’s Global Assessment of PN Stage ...................................23 
6.1.3 
Dermatology Life Quality Index ..........................................................23 
6.1.4 
Photographs..........................................................................................24 
6.2 
Safety Parameters.............................................................................................24 
6.2.1 
Vital Signs ............................................................................................24 
6.2.2 
Physical Examination...........................................................................24 
6.2.3 
Clinical Laboratory Assessments .........................................................24 
6.2.4 
Electrocardiogram ................................................................................25 
6.2.5 
Hospital Anxiety and Depression Scale ...............................................25 
6.2.6 
Epworth Sleepiness Scale ....................................................................26 
6.2.7 
Assessment of Potential for Physical Dependence ..............................26 
6.3 
Subject Flow Diagram .....................................................................................26 
6.4 
Study Visits ......................................................................................................26 
6.4.1 
Baseline Visit .......................................................................................26 
6.4.2 
Week 4 Visit ........................................................................................28 
6.4.3 
Week 8 Visit ........................................................................................28 
6.4.4 
Week 12 Visit ......................................................................................29 
6.4.5 
Week 20 Visit ......................................................................................30 
6.4.6 
Week 28 Visit ......................................................................................31 
6.4.7 
Week 36 Visit ......................................................................................32 
6.4.8 
Week 44 Visit ......................................................................................32 
6.4.9 
Week 52 Visit ......................................................................................33 
6.4.10 
Early Treatment Discontinuation Visit ................................................34 
6.4.11 
Post-Drug Observation Visits ..............................................................35 
6.4.12 
Early Termination ................................................................................36 
7 
ASSESSMENT OF SAFETY ................................................................................36 
7.1 
Definitions........................................................................................................36 
7.1.1 
Adverse Event ......................................................................................36 
7.1.2 
Serious Adverse Event .........................................................................36 
7.1.3 
Abnormal Physical Exam, Laboratory, Vital Sign, and 
Electrocardiogram Findings .................................................................37 
7.1.4 
Deaths ..................................................................................................38 
7.1.5 
Pregnancies and Contraception Requirements for Females .................38 
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7.1.6 
Worsening of Pruritus or Underlying Pruritic Skin Disease ................39 
7.2 
Methods and Timing for Recording and Reporting Adverse Events ...............39 
7.2.1 
Adverse Event Reporting Period .........................................................39 
7.2.2 
Eliciting Adverse Events......................................................................40 
7.2.3 
Assessment of Severity ........................................................................40 
7.2.4 
Assessment of Causality ......................................................................41 
7.3 
Follow-up of Adverse Events and Serious Adverse Events ............................41 
7.4 
Reporting Serious Adverse Events to the Sponsor and Institutional Review 
Board (IRB) or Ethics Committee (EC)...........................................................41 
7.5 
Reporting Serious Adverse Events to Regulatory Authorities and Study 
Investigators .....................................................................................................42 
8 
STATISTICAL METHODS ..................................................................................42 
8.1 
Handling of Missing Data and Excluded Therapy Use ...................................42 
8.2 
Analysis Population .........................................................................................42 
8.3 
Subject Disposition ..........................................................................................42 
8.4 
Subject Characteristics .....................................................................................42 
8.5 
Concomitant Medications ................................................................................43 
8.6 
Treatment Compliance and Extent of Exposure ..............................................43 
8.7 
Efficacy Analyses ............................................................................................43 
8.8 
Safety Analyses ................................................................................................43 
8.8.1 
Adverse Events ....................................................................................43 
8.8.2 
Clinical Safety Laboratory Results ......................................................44 
8.8.3 
Vital Signs ............................................................................................44 
8.8.4 
Electrocardiograms ..............................................................................44 
8.8.5 
Physical Exams ....................................................................................44 
8.8.6 
Menstrual Diaries .................................................................................44 
8.8.7 
Hospital Anxiety and Depression Scale ...............................................44 
8.8.8 
Epworth Sleepiness Scale ....................................................................45 
9 
ADMINISTRATIVE ASPECTS ...........................................................................45 
9.1 
Changes to the Protocol ...................................................................................45 
9.2 
Study Termination ...........................................................................................45 
9.3 
Monitoring and Auditing Procedures...............................................................45 
9.4 
Transfer of Obligations ....................................................................................45 
9.5 
Informed Consent.............................................................................................46 
9.6 
Communication with the Institutional Review Board or Ethics Committee ...46 
9.7 
Disclosure and Confidentiality ........................................................................46 
9.8 
Records and Electronic Case Report Forms ....................................................46 
9.9 
Good Clinical Practice and Ethical Study Conduct .........................................47 
9.10 
End of Study Notification ................................................................................47 
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9.11 
Publication of Results ......................................................................................47 
9.12 
Final Report .....................................................................................................48 
10 
REFERENCES ......................................................................................................49 
 
LIST OF APPENDICES 
Appendix A  Schedule of Activities and Assessments ..........................................................51 
Appendix B  List of Strong CYP3A4 Inhibitors ...................................................................52 
Appendix C  Worst Itch Numeric Rating Scale Questionnaire .............................................53 
Appendix D 
Investigator’s Global Assessment of Prurigo Nodularis: Stage .......................54 
Appendix E 
Dermatology Life Quality Index ......................................................................55 
Appendix F 
Hospital Anxiety and Depression Scale ...........................................................56 
Appendix G  Epworth Sleepiness Scale ................................................................................57 
 
LIST OF TABLES 
Table 1 
Adverse Event Grading ..............................................................................40 
  
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS   
Abbreviation 
Definition 
ACTH 
Adrenocorticotropic hormone, corticotropin 
AD 
Atopic dermatitis  
ADL 
Activities of daily living 
AE 
Adverse event 
ALT 
Alanine aminotransferase  
AMH 
Anti-Mullerian hormone 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Classification 
CYP3A4 
Cytochrome P-450 3A4  
DLQI 
Dermatology Life Quality Index 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
ESS 
Epworth Sleepiness Scale 
ETD 
Early Treatment Discontinuation 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
FSH 
Follicle-stimulating hormone 
HADS 
Hospital Anxiety and Depression Scale 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IGA PN-S 
Investigator’s Global Assessment of Prurigo Nodularis Stage 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System  
LDH 
Lactate dehydrogenase 
LH 
Luteinizing hormone 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NK1-R 
Neurokinin-1 receptor 
NRS 
Numeric rating scale  
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PN 
Prurigo nodularis 
QOL 
Quality of life 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan  
SP 
Substance P 
TEAE 
Treatment-emergent adverse event 
TSH 
Thyroid stimulating hormone 
VAS 
Visual Analog Scale 
WI-NRS 
Worst-Itch Numeric Rating Scale 
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1 
INTRODUCTION 
1.1 
Pruritus  
Pruritus, or itch, is defined as an unpleasant sensation that evokes a desire to scratch 
(Ikoma 2006). Itch and pain, although closely related, are distinct sensations: itch elicits a 
scratching response, whereas pain causes a withdrawal response.  
Emerging research in neurobiology has greatly expanded the understanding of pruritus 
signaling. Pruritoceptors (itch-sensory nerve fibers) consist of two distinct classes of nerve 
fibers: histamine-responsive mechanoinsensitive C-fibers, and histamine-unresponsive 
mechanosensitive polymodal C and A fibers that are activated by cowhage (highly pruritic 
spicules from the pods of the cowhage plant Mucuna pruriens) (Schmelz 2015). The second 
class of histamine-unresponsive, cowhage-responsive nerve fibers has been of particular 
interest in pruritus research, as C-fibers that have a strong and sustained response to 
histamine comprise only about 20% of the overall mechanoinsensitive C-fiber population 
(Steinhoff 2006), and a significant proportion of chronic pruritic conditions do not appear to 
involve histamine-mediated pruritus signaling (Ikoma 2006). Substance P (SP) is a prominent 
pruritogen (itch mediator) in this histamine-independent pruritus pathway (Chuquilin 2016).  
Pruritus stimuli in the skin are transmitted via sensory neurons that have their cell bodies in 
the dorsal root ganglia (DRG) and are linked to second-order neurons in the spine 
(Carstens 2016, Luo 2015). Following activation of these DRG sensory neurons, the pruritus 
signal is transmitted to the second-order spinal neurons primarily by SP, gastrin-releasing 
peptide, and glutamate in histamine-independent pruritus, and primarily by glutamate in 
histamine-mediated pruritus (Chuquilin 2016). 
Spinal itch neuron projections ascend via the contralateral spinothalamic tract to the thalamus 
and via the lateral spinoparabrachial tract to the lateral parabrachial nucleus, from which 
point they activate multiple centers in the somatosensory cortex, the premotor cortex, and the 
cingulate cortex – areas involved in the sensory processing and motor response (scratching) 
to the itch signal (Carstens 2016, Chuquilin 2016). 
1.1.1 
Role of Substance P and the Neurokinin-1 Receptor in Pruritus 
Substance P is an undecapeptide that belongs to the tachykinin family of neuropeptides, a 
group that also includes neurokinin A and neurokinin B (Hökfelt 2001). SP has been 
implicated in a number of biological functions, both physiological and pathophysiological, 
including pruritus perception, vomiting reflex, pain perception, and immunomodulatory 
responses (Lotts 2014, Andoh 1998, Steinhoff 2014).  The biological actions of SP are 
mediated by tachykinin receptors, which consist of seven hydrophobic transmembrane 
domains coupled to G-proteins. Three tachykinin receptors have been identified: the 
neurokinin-1 (NK1-R), neurokinin-2, and neurokinin-3 receptors (Harrison 2001). The 
neurokinin-1 receptor, in particular, has been studied in great detail. NK1-R is the primary 
receptor for SP in the human body, and is found on multiple cell types, including central and 
peripheral neurons, keratinocytes, mast cells, and dendritic cells (El-Nour 2006, 
Ständer 2015).  
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NK1-R stimulation has been shown to be an important pathway for pruritus perception 
(Ständer 2015). Inhibition of this pathway results in decreased pruritus and scratching 
reflexes in animal models (Akiyama 2015). Preceding the development of serlopitant for 
pruritus-related conditions, a commercially available NK1-R antagonist (Emend USPI) has 
been used as a therapy to decrease pruritus in patients with chronic pruritus due to etiologies 
such as cutaneous T-cell lymphoma (Duval 2009, Torres 2012, Booken 2011) and erlotinib-
induced pruritus (Santini 2012, Gerber 2010). Additionally, in a study of 20 patients with 
chronic pruritus of various etiologies treated with aprepitant, 16/20 patients (80%) 
experienced a considerable reduction of itch intensity (Ständer 2010).  
1.2 
Serlopitant  
1.2.1 
Serlopitant Background and Nonclinical Summary 
Serlopitant is a small molecule, highly selective NK1-R antagonist that is administered orally 
and metabolized by cytochrome P-450 3A4 (CYP3A4), with a plasma half-life of 45-86 
hours. It binds with high affinity to the human NK1-R with a dissociation constant (Kd) of 46 
pM; displacing SP binding with a half-maximal inhibition concentration (IC50) of 61 pM. 
Serlopitant is a potent functional antagonist of SP-induced inositol phosphate generation. 
Serlopitant has been extensively studied in animal toxicology studies, including chronic 
toxicology and carcinogenicity studies. In non-clinical chronic toxicology studies in rats, 
mice and dogs, treatment related findings of potential clinical significance included increased 
salivation, decreased body weight gain and food consumption, slight changes in hematology 
and serum biochemistry parameters, mild increases in liver weight and mild 
histomorphologic changes. The histomorphologic changes were seen only in rats (not in dogs 
or mice) and included: very slight ovarian interstitial cell hypertrophy, mammary gland and 
uterine atrophy; decreased corpora lutea; increased histiocytes in lung and mesenteric lymph 
nodes; slight skeletal and cardiac muscle degeneration; slight increased hematopoiesis in 
bone marrow; and slight to moderate vacuolation in kidney tubules. These nonclinical 
findings occurred at systemic exposures exceeding those anticipated to provide efficacy of 
serlopitant for pruritus indications in humans (1 to 5 mg tablet daily). No cardiac lesions have 
been observed in dog toxicity studies up to 9 months in duration nor in a 3-month mouse 
range-finding study and 2-year mouse carcinogenicity study at exposure higher than the 
lowest level which caused cardiotoxicity in rats. The no observed adverse effect level 
(NOAEL) in rats for histomorphological changes in the reproductive tract, mammary gland 
and bone marrow provides a 2.5-fold margin for the maximum-targeted exposure (5 mg 
tablet daily). The rat NOAEL for histomorphological changes in muscle and kidney provides 
a 5-fold margin for the maximum-targeted exposure (5 mg tablet daily).  
In summary, the nonclinical toxicity noted with serlopitant provides no contraindications to 
the continuation of clinical trials via the oral route. Findings in the developmental toxicity 
studies support inclusion of women of childbearing potential in clinical trials in accordance 
with the study protocol and local regulatory guidances.  
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1.2.2 
Serlopitant Clinical Summary 
In humans, serlopitant has been administered to over 1000 individuals. Single doses up to 
400 mg have been well tolerated in young adult males and single doses up to 25 mg have 
been well tolerated in the elderly. Multiple doses of up to 50 mg a day for 4 weeks have been 
well tolerated in healthy young males, and a single (loading) dose of 15 mg followed by daily 
doses of 5 mg for 2 weeks have been well tolerated in elderly males and females. Forty-one 
(41) subjects received 4 mg liquid filled capsule (LFC) daily (bioequivalent to 5 mg tablets) 
for 1 year. Plasma concentrations of serlopitant appear to increase in a dose-proportional 
fashion in both young males and elderly subjects (males and females). Peak plasma 
concentrations after a single oral dose occurred at ~2 to 4 hours in both young and elderly 
subjects. A single loading dose of up to 15 mg followed by 6 to 8 weeks of up to 5 mg daily 
doses has been well tolerated in adults with chronic pruritus and prurigo nodularis (PN). 
Pharmacokinetic data demonstrate good plasma exposures with oral dosing, linear dose-
dependent increases in plasma concentration and systemic exposure, a plasma t1/2 
appropriate for once daily dosing, and mild effects of concomitant food ingestion. Central 
nervous system (CNS) positron emission tomography (PET) studies have demonstrated good 
CNS penetrance and > 90% NK1 receptor occupancy (RO) at plasma exposures anticipated 
to be safe and well tolerated. Three long-lived active hydroxylated metabolites are observed 
in humans: M1/M1a 
, M2/M2a 
, and M3 
. 
These metabolites were present at lower concentrations and were 2- to 9-fold less potent in 
vivo than the parent compound. The integrated pharmacokinetic/pharmacodynamic (PK/PD) 
analysis concluded that these metabolites are unlikely to contribute significantly to 
occupancy of the CNS NK1-R in humans. 
1.2.3 
Serlopitant in Pruritus-Related Studies 
Serlopitant has been evaluated in two completed Phase 2 studies of subjects with chronic 
pruritus (TCP-101 and TCP-102).  
TCP-101 
TCP-101 was a double-blind, placebo-controlled, multi-center study that compared 
serlopitant 0.25 mg, 1 mg, or 5 mg vs. placebo for the treatment of chronic pruritus. A total 
of 257 adult subjects 18-65 years of age with chronic pruritus were randomized to receive 
one of the four dose groups in a 1:1:1:1 randomization. Subjects received a loading dose of 
3 tablets on Day 1 and thereafter received 1 tablet per day for 6 weeks. The primary efficacy 
endpoint was itch severity as measured on a Visual Analog Scale (VAS), summarized as a 
percentage change from baseline. 
Mean percent decreases from Baseline in VAS score were larger in the active-treatment 
groups versus placebo at every scheduled post-baseline study visit. Overall, the results were 
the most profound for the serlopitant 1 mg and 5 mg groups. For the percent change from 
Baseline in VAS pruritus scores (the primary efficacy variable), the Week 6 pairwise least 
squares mean difference compared to placebo was 5.8 mm, 13.2 mm, and 14.2 mm for 
serlopitant 0.25 mg, 1 mg, and 5 mg, respectively.   
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The frequency of treatment-emergent adverse events (TEAEs) and study drug related adverse 
events (AEs) was higher in the serlopitant 1 mg and 5 mg groups compared to the serlopitant 
0.25 mg group, and the frequency in all three treatment groups were higher than in the 
placebo group. The frequency of AEs leading to study drug discontinuation was comparable 
in the serlopitant 5 mg and placebo group and higher than in the serlopitant 0.25 mg and 
1 mg groups. There was one serious adverse event (SAE) reported in the serlopitant 1 mg 
group (spontaneous abortion, considered not related). There were no deaths. The most 
common AEs in the serlopitant groups were diarrhea (6.2%, 1 mg group), upper respiratory 
tract infection (4.7%, 0.25 mg group), somnolence (4.7%, 5 mg group), nasopharyngitis 
(4.6%, 1 mg group), headache (4.7%, 5 mg group), urinary tract infection (3.1%, 5 mg 
group), dry mouth (3.1%, 1 mg group), nausea (3.1%, 1 mg group), arthralgia (3.1%, 0.25 
mg group), musculoskeletal pain (3.1%, 1 mg group) and pruritus (3.1%, 1 mg group). The 
most common AEs in the placebo group were headache (6.3%), nasopharyngitis (3.2%), 
upper respiratory tract infection (3.2%), urinary tract infection (3.2%) and asthma (3.2%).  
TCP-102 
TCP-102 was a randomized, double-blind, placebo-controlled multi-center study that 
evaluated serlopitant 5 mg vs. placebo for the treatment of PN A total of 128 adult subjects 
18-80 years of age with PN were randomized to receive serlopitant or placebo in a 1:1 
randomization. Subjects received a loading dose of 3 tablets on Day 1 followed by 1 tablet 
per day for 8 weeks. The primary efficacy endpoint was the average VAS score as recorded 
at the study visits. Results at Week 4 and Week 8 were the primary timepoints. 
Serlopitant 5 mg was superior to placebo for the reduction of pruritus as measured by change 
in average VAS from baseline. For the primary endpoint, change from baseline at Week 4 
and Week 8 by repeated measures analysis, the decrease from baseline was significantly 
greater in the serlopitant group than the placebo group, with a mean difference (serlopitant 
minus placebo) of -1.0 at Week 4 and -1.7 at Week 8. The mean difference at Week 2 was 
also significant, -0.9. In a post-hoc analysis of the percentage of subjects who were 4-point 
responders on average VAS at Week 8, 25.0% of placebo subjects and 54.4% of serlopitant 
subjects were 4-point responders. 
TEAEs were reported for 71.9% of serlopitant-treated subjects and 61.9% of placebo-treated 
subjects. The most frequently reported TEAEs in the serlopitant group were nasopharyngitis 
(17.2% serlopitant, 3.2% placebo), diarrhea (10.9% serlopitant, 4.8% placebo), and fatigue 
(9.4% serlopitant, 6.3% placebo). Treatment-related TEAEs were reported for 48.4% of 
serlopitant-treated subjects and 34.9% of placebo-treated subjects. The most frequently 
reported treatment-related TEAEs in the serlopitant group were fatigue (7.8%) and diarrhea, 
peripheral edema, dizziness, and headache (each 6.3%). Most TEAEs were mild or moderate; 
severe TEAEs were reported for 9.4% of serlopitant-treated subjects and 4.8% of placebo-
treated subjects. There were no deaths during the study. Five subjects (3 serlopitant, 
2 placebo) had SAEs. The SAEs were actinic elastosis, depression, dizziness, and vertigo in 
the serlopitant group; and bradycardia, syncope, respiratory failure, and neurodermatitis in 
the placebo group. Nine subjects (3 serlopitant, 6 placebo) discontinued due to TEAEs. 
No clinically relevant changes were observed in chemistry, hematology, vital signs, or 
electrocardiogram (ECG) results. 
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The results of the Phase 2 studies in PN and chronic pruritus, together with the extensive 
nonclinical and clinical safety data and experience with serlopitant to date and the scientific 
rationale for NK1-R inhibition in the treatment of pruritus, serve to support further evaluation 
of serlopitant for the long-term treatment of pruritus in patients with PN, AD, or psoriasis. 
The potential benefits of continued clinical study outweigh the potential risks. The data 
obtained from this long-term study will inform the risks and benefits of long-term exposure 
(chronic or repeated intermittent use for longer than 6 months). The risk to subjects in this study 
will be minimized by medical and safety monitoring (see Section 3.4.1). 
Please refer to the Investigator’s Brochure for further information regarding serlopitant. 
2 
STUDY OBJECTIVES  
The primary objective of this study is to assess the long-term safety of serlopitant in adults 
with pruritus associated with PN, AD, or psoriasis. 
The secondary objectives of this study are to assess the change in severity of pruritus in 
subjects with PN, AD, or psoriasis using the worst-itch numeric rating scale (WI-NRS); to 
assess the change in severity and extent of PN using the Investigator’s Global Assessment of 
PN Stage (IGA PN-S), for those subjects with PN; and to assess whether serlopitant produces 
physical dependence. 
3 
STUDY DESIGN 
3.1 
Overall Study Design 
This is a multicenter, open-label study to assess the long-term safety of serlopitant in adults 
with pruritus associated with PN, AD, or psoriasis. Eligible subjects who have completed 
selected studies of serlopitant may be given the opportunity, at the investigator’s discretion, 
to consent to and participate in this open-label study, regardless of their treatment allocation 
in prior studies. If deemed necessary by Menlo Therapeutics to meet enrollment objectives, 
eligible subjects who have not participated in a prior serlopitant study may also be enrolled in 
study MTI-107. Approximately 120 study sites may enroll subjects in this long-term safety 
study. 
This study will consist of two periods, for a total study period of approximately 57 weeks: 
• Treatment period: 52 weeks 
• Post-drug observation period: 5 weeks 
 
During the treatment period, subjects will take one serlopitant 5 mg tablet once daily orally 
(Section 5.3).  
Standard therapy for the concurrent skin lesions and pruritus may be employed during this 
study (Section 5.7.1).  
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The WI-NRS during a 24-hour recall period will be assessed by the subject at each study 
visit. 
For those subjects with PN, the severity and extent of PN will be assessed at selected visits, 
using the IGA-PN-S, and photographs of representative areas with PN will be taken at 
selected visits at a subset of sites. 
The Dermatology Life Quality Index (DLQI) will be administered at selected visits. 
After completion of the 52-week treatment period, all subjects will enter a 5-week post-drug 
observation period. Subjects who discontinue treatment early will have a post-drug 
observation visit through 5 weeks after their last dose of serlopitant. During this monitored 
discontinuation period, solicited safety evaluations will assess the potential for serlopitant to 
produce physical dependence. 
3.2 
Rationale for Study Design and Dose Selection 
The current MTI-107 study is designed to confirm the long-term safety of serlopitant for the 
treatment of pruritus in patients with PN, AD, and psoriasis. The 5 mg dose of serlopitant 
was selected for this study based on the favorable efficacy, safety, and tolerability profile of 
serlopitant at this dose level in completed studies.  
3.3 
Study Endpoints 
3.3.1 
Safety Endpoints 
The safety endpoints are as follows: 
• Incidence of TEAEs and SAEs 
• Change from baseline in clinical laboratory parameters   
• Change from baseline in vital sign and ECG parameters 
• Change from baseline in the Hospital Anxiety and Depression Scale (HADS)  
• Change from baseline in the Epworth Sleepiness Scale (ESS)   
• Assessment of physical dependence following chronic study drug exposure, in the 
5-week post-drug discontinuation period.  
 
3.3.2 
Efficacy Endpoints 
The efficacy endpoints are as follows: 
• Change from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52  
• Change from baseline in DLQI (symptoms and feelings, daily activities, leisure, work or 
school performance, personal relationships, and treatment) to Weeks 20, 36 and 52 
• Change from baseline in IGA PN-S to Weeks 4, 8, 20, 28, 36, 44, and 52 
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3.4 
Safety Review 
3.4.1 
Safety Monitoring Team 
An internal safety monitoring team consisting of representatives from Menlo Therapeutics 
Inc. and its designees will monitor safety data on a regular basis throughout the study. 
4 
SELECTION OF STUDY POPULATION 
4.1 
Study Population 
Approximately 400 adult subjects with pruritus associated with PN, AD, or psoriasis will be 
enrolled in this study. 
4.2 
Inclusion Criteria 
Subjects must meet the following criteria to be enrolled into the study: 
1. Male or female, age 18 years or older at consent. 
2. Subject reports pruritus in the 24-hour period prior to enrollment and: 
a. Has completed a prior applicable clinical study of serlopitant without an SAE 
that was assessed as likely related to the study drug (For participants from 
study TCP-102, the WI-NRS score must be ≥ 7 in the 24-hour period prior to 
the Baseline visit.) 
OR  
b. Has not participated in a prior clinical study of serlopitant and has a clinical 
diagnosis of PN, AD, or psoriasis, and has a WI-NRS score ≥ 7 in the 24-hour 
period prior to the Baseline visit, and Sponsor has approved enrollment. 
3. All female subjects who are of childbearing potential must be willing to practice highly 
effective contraception (i.e., pregnancy prevention method with a failure rate of <1% per 
year, refer to Section 7.1.5 for acceptable methods of contraception) from the time of the 
Baseline visit until 5 weeks after last dose of study drug. 
4. Willing and able (has adequate cognitive ability, in the investigator’s opinion) to comply 
with study visits and study related requirements including providing written informed 
consent. 
 
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4.3 
Exclusion Criteria 
Subjects who meet any of the following criteria are not eligible for participation in the study: 
1. Presence of malignancy within 5 years prior to enrollment (exception for non-melanoma 
cutaneous malignancies). 
2. Any known major psychiatric diagnosis, such as major depressive disorder, bipolar 
disorder, schizophrenia, psychotic disorder, intellectual disability, severe alcohol use 
disorder, which may confound the assessment of serlopitant safety or efficacy, or 
interfere with the subject’s ability to comply with protocol-mandated activities, within 3 
years prior to enrollment.   
3. Untreated or inadequately treated thyroid, adrenal, or pituitary nodules or disease, or 
history of thyroid malignancy; or the presence of any medical condition or disability, 
that, in the investigator’s opinion, could interfere with the assessment of safety in this 
study or compromise the safety of the subject.  
4. Treatment with any investigational therapy within 4 weeks or 5-half-lives prior to 
enrollment (whichever is longer) or expected participation in another clinical study 
involving an investigational product or device during the subject’s participation in MTI-
107. 
5. Treatment with other neurokinin-1 receptor (NK1-R) antagonists (e.g., aprepitant, 
fosaprepitant, rolapitant) within 4 weeks prior to enrollment. 
6. Treatment with strong cytochrome P450 3A4 inhibitors within 4 weeks prior to 
enrollment (Appendix B). 
7. Currently pregnant or breastfeeding or planning to become pregnant during the study. 
 
5 
STUDY DRUG 
5.1 
Study Drug Supply, Route of Administration, and Storage 
The study drug in this study is serlopitant 5 mg in a film-coated tablet formulation for oral 
administration. The serlopitant tablets contain microcrystalline cellulose, mannitol, 
croscarmellose sodium, silicon dioxide, sodium lauryl sulfate, and magnesium stearate, and 
are film coated with Opadry® Brown.  
The study drug will be provided in bottles that can be stored at room temperature (59-86°F, 
15-30°C). 
Each bottle will each contain 18 serlopitant tablets.  
Additional details regarding study drug supplies can be found in the Pharmacy Manual. 
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5.2 
Labeling and Study Drug Accountability 
The study drug will be appropriately packaged and labeled in bottles with 18 tablets per 
bottle. The study drug supplied for this study is not to be used for any purpose other than this 
study, and study drug accountability must be maintained for all bottles distributed to the 
investigative site. 
Additional details regarding study drug labeling and accountability can be found in the 
Pharmacy Manual. 
5.3 
Dosing Regimen 
During the treatment period, subjects will take one serlopitant 5 mg tablet once daily orally.  
Subjects will be instructed to take all doses from Baseline Visit (Study Day 1) until the Week 
52 Visit, once a day. Study drug may be taken with or without food. 
Should the study drug be withheld (without intent to discontinue study drug, Section 5.6), the 
drug may be resumed at the discretion of the investigator, at the same dosing regimen.  
5.4 
Dose Modification 
No dose modification of study drug will be allowed during this study.  
5.5 
Missed or Delayed Doses 
Each dose of study drug after the first dose must be administered once daily. If a dose is 
missed, that dose will be considered and documented as a missed dose.  Dosing should 
resume as directed the next day. 
5.6 
Study Drug Discontinuation 
Subjects should be discontinued from study drug in the following situations: 
• Any medical condition that may jeopardize the subject’s safety if study drug is continued, 
in the investigator’s and/or Sponsor’s opinion; this may include the development of 
persistently (2 successive occasions) abnormal thyroid function tests (TSH >10, or 
TSH > 6 with low free T4; TSH <0.1, or TSH < 0.35 with high free T4); abnormal 
morning prolactin, cortisol, or corticotropin levels; or signs and symptoms of adrenal 
insufficiency 
• Baseline serum creatinine, total bilirubin, alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) > 2.5 times the upper limit of normal (ULN) (exception may be 
made for retesting within 28 days of enrollment as approved by the Medical Monitor) 
• A female subject desires to become pregnant at the current time, stops contraception or 
expels her intrauterine device/implant, or becomes pregnant 
• A female subject has new breast findings (e.g. a palpable mass or abnormal 
mammography, discharge), or has abnormal vaginal discharge or bleeding 
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• The subject decides to discontinue study drug, or withdraws consent from the study 
• The subject reports use of a strong CYP3A4 inhibitor (as listed in Appendix B) within 4 
weeks of the study visit at which it was reported, initiates any investigational medication, 
or other NK1-R antagonist (exception may be made for use of approved NK1-R 
antagonist for less than 5 continuous days) 
• Discontinuation is deemed to be in the best interest of the subject, in the investigator’s 
and/or Sponsor’s opinion, including evidence that the subject does not meet 
inclusion/exclusion criteria intended primarily for safety reasons, or a persistent lack of 
adherence to study procedures 
 
The Sponsor or designee should be contacted within 24 hours of investigator’s awareness of 
any study drug discontinuation due to an AE or pregnancy. Investigators should make every 
effort to contact the Sponsor or designee before discontinuing study drug, if possible. 
Subjects who discontinue study drug prior to completing the treatment period will enter a 
5-week follow-up period following the last dose of study drug (Section 6.4.10). Every effort 
should be made for subjects to complete this follow-up visit after a subject has discontinued 
from study drug.  
5.7 
Concomitant and Excluded Therapies 
Concomitant therapies include any therapies (including over-the-counter medications) used 
by a subject from initiation of study drug through the follow-up period. A record of all 
medications used will be maintained for each subject throughout the study. Reported 
information will include a description of the type of drug, treatment period, dosing regimen, 
the route of administration, and drug indication. The use of any concomitant medication must 
relate to the subject’s medical history or to an AE, except for vitamins/nutritional 
supplements and routine preventative immunizations.  
5.7.1 
Excluded Therapies 
The following therapies and activities are excluded from the Baseline visit through the 
follow-up period: 
• NK1-R antagonists (other than study drug, exception may be made for use of approved 
NK1-R antagonist for less than 5 continuous days) 
• Strong CYP3A4 inhibitors (See Appendix B; exceptions may be made for use within 4 
weeks of the study visit at which it was reported) 
• Any investigational drug therapy other than serlopitant 
 
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Use of any excluded therapies should be reported as soon as possible, and will be recorded as 
protocol deviations for subjects who receive them. Subjects may be discontinued from the 
study drug (Section 5.6). 
5.8 
Assignment to Treatment  
Eligible subjects will receive serlopitant 5 mg tablets. 
5.9 
Treatment Compliance 
Records of study drug used, dosages administered, and intervals between visits will be kept 
during the study. Subjects will be asked to return all partially used and empty bottles to the 
study site at each visit. The site staff will count and record the number of remaining tablets in 
each returned bottle. Missed doses will be recorded as reported by the subject. A subject who 
has deviated significantly from the once-daily dosing regimen will be counseled. 
6 
STUDY SCHEDULE AND ASSESSMENTS  
6.1 
Efficacy Parameters 
6.1.1 
Itch Numeric Rating Scale 
The Itch NRS is a validated, self-reported instrument for measurement of itch intensity. WI-
NRS scores will be captured as per Appendix A. Subjects are asked to rate the intensity of 
their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher 
scores indicate greater itch intensity. In this study, the subject is asked to rate the intensity of 
their worst itch (WI-NRS) during a 24-hour recall period prior to the specified visit; the 
questionnaire is provided in Appendix C.   
6.1.2 
Investigator’s Global Assessment of PN Stage 
The IGA PN-S is an instrument used to assess the overall number and thickness of PN 
lesions at a given time point, as determined by the investigator. It consists of a 5-point scale 
ranging from 0 (clear) to 4 (severe), as provided in Appendix D. The IGA PN-S uses clinical 
characteristics including the number of nodules and their thickness, as guidelines for the 
overall severity assessment. IGA PN-S scores will be captured as per Appendix A. Each 
assessment during the study must be done by the principal investigator (PI) or designee. 
Every effort should be made to ensure that all assessments for a given subject are done by the 
same individual throughout the study. However, a change in assessor for a given subject, 
though not ideal, will not be considered a protocol deviation. 
6.1.3 
Dermatology Life Quality Index  
DLQI is a dermatology specific quality of life instrument designed to assess the impact of the 
skin disease on a subject’s quality of life over the prior week. It is a ten-item questionnaire 
that assesses overall quality of life (QOL) and six aspects that may affect QOL (symptoms 
and feelings, daily activities, leisure, work or school performance, personal relationships, and 
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treatment), and is provided in Appendix E. The DLQI questionnaire will be collected as per 
Appendix A. 
6.1.4 
Photographs 
At selected investigative sites, optional photographs of representative areas with PN 
involvement will be taken at multiple time points, as per Appendix A. These areas may 
include the extensor surfaces of both arms and both legs (overview of both legs, detail of 
lower legs), and the abdomen and back. The central photography vendor will provide 
photographic equipment to the sites for use during the study. Detailed instructions will be 
provided in a Photography Manual. 
6.2 
Safety Parameters 
Safety assessments will consist of monitoring and recording protocol-defined AEs and SAEs; 
vital signs; physical examinations; clinical laboratory assessments; ECGs; and other 
protocol-specified tests that are deemed critical to the safety evaluation of the study drug. 
6.2.1 
Vital Signs 
Vital signs will include measurements of heart rate, blood pressure, respiration rate, and 
temperature after the subject has been calmly resting (seated or supine) for a minimum of 
5 minutes. Vital signs will be assessed as per Appendix A and at unscheduled study visits 
when clinically indicated. When possible, assessment of vital signs should precede blood 
draw.  
6.2.2 
Physical Examination 
Physical examinations will be performed as per Appendix A and at unscheduled study visits 
when clinically indicated. A complete physical examination will be performed at the 
Baseline visit, while subsequent examinations will be abbreviated and targeted to changes in 
disease activity and/or subjects’ symptoms. The subjects’ height and weight will be measured 
as per Appendix A. For female subjects with targeted breast examinations, please perform 
breast examination after blood draw for clinical laboratory tests.   
6.2.3 
Clinical Laboratory Assessments 
Samples for clinical laboratory assessments will be collected as per Appendix A and at 
unscheduled study visits when clinically indicated, and analyzed at a central laboratory 
unless otherwise specified. When possible, blood draws should follow ECGs and vital sign 
measurements if they occur on the same visit.  
Detailed instructions regarding sample collection, preparation, and shipment can be found in 
the laboratory manual. Laboratory assessments will include the following, and are ideally 
performed in the morning, particularly at visits with endocrine assessments (Baseline, Weeks 
12, 28, and 52): 
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• Hematology: hematocrit, hemoglobin, red blood cell count, red blood cell indices, 
platelets, white blood cell count, white blood cell differential (neutrophils, lymphocytes, 
monocytes, basophils, eosinophils) 
• Chemistry: sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, 
creatinine, calcium, phosphorus, magnesium, albumin, uric acid, total protein, alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total 
bilirubin, lactate dehydrogenase (LDH), lipid panel 
• Endocrine: TSH, free T4, cortisol, corticotropin (adrenocorticotropic hormone, ACTH), 
prolactin  
- 
Standard cosyntropin stimulation testing should be performed on subjects with low 
cortisol level (i.e. < 3.0 mcg/dL); the investigator should discuss low cortisol (and 
relevant low corticotropin) results with the medical monitor. 
• Pregnancy testing: all females of childbearing potential will have a local urine pregnancy 
test performed. Monthly pregnancy testing can be performed in between visits (and 
recorded as an Unscheduled visit), and at any time per the investigator’s discretion, and  
as required by local authorities (e.g. in Austria). Positive or equivocal urine pregnancy 
test results will be confirmed by a serum pregnancy test analyzed at a central laboratory 
• Reproductive endocrinology (for all female subjects under 55 years of age at consent): 
serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, 
progesterone, anti-Mullerian hormone (AMH)  
• For participants from study TCP-102 or those who had not participated in a prior clinical 
study of serlopitant, additional optional studies for the etiology of PN (if applicable) will 
be supported through local procedural and/or laboratory assessments (test kits not 
supplied by Sponsor). Studies may include, but are not limited to, iron studies (ferritin, 
serum iron), serum IgE, hepatitis B and C serology, HIV testing, skin biopsy and 
pathology interpretation, urea breath test for Helicobacter pylori, and allergy testing 
(patch, prick, or blood testing); the investigator should discuss the need for such studies 
with the medical monitor during the Screening period 
 
6.2.4 
Electrocardiogram  
A standard 12-lead ECG will be performed after the subject has been calmly resting in a 
supine position for a minimum of 5 minutes before obtaining the ECG. When possible, ECGs 
should precede measurement of vital signs and blood draw for clinical laboratory tests. ECGs 
will be performed as per Appendix A and at unscheduled study visits when clinically 
indicated. ECGs will be reviewed and reported by a central ECG vendor. The ECG machine 
and detailed instructions will be provided by the ECG vendor. 
6.2.5 
Hospital Anxiety and Depression Scale 
The HADS is a QOL instrument designed to assess the severity of anxiety and depression 
over the prior week, developed in a hospital outpatient clinic, but also valid in community 
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settings and primary care medical practice.  The questionnaire takes approximately 2 to 5 
minutes to complete, and is provided in Appendix F. The HADS questionnaire will be 
collected as outlined in Appendix A. 
6.2.6 
Epworth Sleepiness Scale 
The ESS is a QOL instrument intended to measure daytime sleepiness by use of a very short 
questionnaire. The questionnaire takes approximately 2 to 3 minutes to complete, and is 
provided in Appendix G. The ESS questionnaire will be collected as outlined in Appendix A. 
6.2.7 
Assessment of Potential for Physical Dependence 
NK1-R antagonist dependence has not previously been described and therefore a drug class-
specific, reliable and sensitive instrument for the assessment of withdrawal symptoms has not 
been developed. A surrogate assessment tool, such as those developed for opioid or 
benzodiazepine dependence, is not available.  
In order to provide a comprehensive set of assessments for physical dependence and 
withdrawal symptoms following chronic exposure to the study drug, the HADS and ESS 
instruments will be administered at baseline and throughout the study period, as well as 3-
days and 7-days following the last dose of study drug, and then weekly throughout the 5-
week post-study drug observation period. In addition, vital signs will be assessed at each 
post-study drug observation visit, and an ECG and laboratory analyses will be assessed at the 
5-week post-study drug visit. All TEAEs reported during this period will be medically 
reviewed to assess for possible physical dependence or withdrawal signs or symptoms. 
6.3 
Subject Flow Diagram 
The visit schedule and assessments are summarized in Appendix A.  
6.4 
Study Visits 
The following sections describe the procedures and assessments to be performed at each 
study visit. Details of each procedure and assessment can be found in Sections 6.1 and 6.2. 
The timing of each study visit is relative to the day of enrollment (Baseline Visit). 
Unscheduled visits may be performed as necessary, and may include procedures or 
assessments deemed necessary by the investigator and to conduct monthly urine pregnancy 
testing on females of childbearing potential in between regularly scheduled visits. 
Female subjects who report periodic menstruation will be asked to complete a menstrual 
diary (paper form) throughout the study. 
6.4.1 
Baseline Visit 
The Baseline Visit may coincide with the final visit of the MTI-103, MTI-105, MTI-106, or 
MTI-109 studies. 
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The following procedures are to be performed at the Baseline Visit (Day 1): 
• Obtain written informed consent prior to any protocol-mandated procedures (must be 
obtained prior to any other assessments) 
• Confirm subject’s eligibility based on the inclusion/exclusion   
• Collect demographic information (when permitted by regional laws or guidelines: sex, 
date of birth, race/ethnicity)  
• Collect any concomitant medications 
• Review and record subject’s medical history, including ongoing TEAEs from prior study 
(if applicable) 
- 
Female subjects should be queried regarding history of, or current, breast masses or 
abnormal discharge, and history of mammography (if applicable), and history of 
abnormal vaginal bleeding or discharge 
• Perform complete physical examination (including height and weight)  
• Obtain ECG  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Draw blood for clinical laboratory tests (exception: participants in MTI-103, MTI-105, 
MTI-106, and MTI-109 who have had these labs in prior 14 days, in the context of that 
study) 
- 
Hematology 
- 
Chemistry 
- 
Endocrine  
- 
Reproductive endocrine labs for females under 55 years of age at consent  
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
DLQI 
- 
HADS 
- 
ESS 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Register Baseline Visit into the Interactive Web Response System (IWRS)  
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• Dispense study drug 
• Provide a menstrual diary to female subjects who report periodic menstruation   
• Confirm next scheduled visit date 
6.4.2 
Week 4 Visit 
The Week 4 Visit occurs 28 days (±7 days) after the Baseline Visit. At the Week 4 Visit, the 
following procedures and assessments are to be performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.3 
Week 8 Visit 
The Week 8 Visit occurs 56 days (±7 days) after the Baseline Visit. At the Week 8 Visit, the 
following procedures and assessments are to be performed:  
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• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.4 
Week 12 Visit 
The Week 12 Visit occurs 84 days (±7 days) after the Baseline Visit. At the Week 12 Visit, 
the following procedures and assessments are to be performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination, including weight  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
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- 
Endocrine  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.5 
Week 20 Visit 
The Week 20 Visit occurs 140 days (±7 days) after the Baseline Visit. At the Week 20 Visit, 
the following procedures and assessments are to be performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
DLQI 
- 
HADS 
- 
ESS 
• Perform IGA PN-S (for subjects with PN only) 
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• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.6 
Week 28 Visit 
The Week 28 Visit occurs 196 days (±7 days) after the Baseline Visit. At the Week 28 Visit, 
the following procedures and assessments are to be performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination, including weight  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
- 
Endocrine 
- 
Reproductive endocrine labs for females under 55 years of age at consent   
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
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6.4.7 
Week 36 Visit 
The Week 36 Visit occurs 252 days (±7 days) after the Baseline Visit. At the Week 36 Visit, 
the following procedures and assessments are to be performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
DLQI 
- 
HADS 
- 
ESS 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.8 
Week 44 Visit 
The Week 44 Visit occurs 308 days (±7 days) after the Baseline Visit. At the Week 44 Visit, 
the following procedures and assessments are to be performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
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• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.9 
Week 52 Visit 
The Week 52 Visit occurs 364 days (±7 days) after the Baseline Visit. At the Week 52 Visit, 
the following procedures and assessments are to be performed:  
• Register visit into the IWRS 
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination, including weight 
• Obtain ECG  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Hematology 
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- 
Chemistry 
- 
Endocrine 
- 
Reproductive endocrine labs for females under 55 years of age at consent  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
DLQI 
- 
HADS 
- 
ESS 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug 
• Confirm next scheduled visit date 
 
6.4.10 
Early Treatment Discontinuation Visit 
The Early Treatment Discontinuation (ETD) Visit occurs within 35 days of last dose for 
subjects who discontinue serlopitant treatment prior to Week 52.  
At the ETD Visit, the following procedures and assessments are to be performed:  
• Register visit into the IWRS 
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination, including weight 
• Obtain ECG   
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
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• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
DLQI 
- 
HADS 
- 
ESS 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug   
 
6.4.11 
Post-Drug Observation Visits 
There are six (6) post-drug observation visits. 
The Post-Drug Observation Visits occur 3 days (±1 days), 7 days (±3 days), 14 days (±3 
days), 21 days (±3 days), 28 days (±3 days), and 35 days (±3 days) after the Week 52 Visit.  
At the Post-Drug Observation Visits, the following procedures and assessments are to be 
performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination, including weight (Only required at post-drug 
observation visit 35 days after Week 52 visit) 
• Obtain ECG (Only required at post-drug observation visit 35 days after Week 52 visit) 
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) (Only required at post-drug 
observation visit 35 days after Week 52 visit) 
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• Draw blood for clinical laboratory tests (Only required at post-drug observation visit 35 
days after Week 52 visit) 
- 
Hematology 
- 
Chemistry 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
HADS 
- 
ESS 
• Register visit into the IWRS (Only at post-drug observation visit 35 days after Week 52 
visit) 
 
6.4.12 
Early Termination 
Early termination of a subject from the study may occur due to loss to follow-up or 
withdrawal of consent by the subject. In accordance with legal requirements and 
International Conference on Harmonization (ICH) – Good Clinical Practice (GCP) 
guidelines, every subject or his/her legal representative has the right to withdraw from the 
study at any time and without providing reasons. If provided, the reason (adverse event, 
study burden, lack of efficacy, other) a subject withdrew consent will be recorded in the 
electronic Case Report Form (eCRF). Attempts to contact subjects who are suspected of 
being lost to follow-up must be documented in the subject’s source documents. 
7 
ASSESSMENT OF SAFETY 
7.1 
Definitions 
7.1.1 
Adverse Event 
An AE is any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. An AE can be any unfavorable and unintended sign 
(e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a drug, without any judgment about causality. 
AEs include treatment emergent exacerbations of pre-existing illnesses and AEs that occur as 
a result of protocol-mandated interventions. 
7.1.2 
Serious Adverse Event  
An AE is considered “serious” if it results in any of the following outcomes: 
• Death 
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• Life-threatening AE (i.e. the subject was at immediate risk of death from the event as it 
occurred. An event that might have led to death if it had occurred with greater severity is 
not “life-threatening”) 
• Inpatient hospitalization or prolongation of existing hospitalization  
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• Congenital anomaly/ birth defect 
• Important medical event (i.e. an event that may not result in death, be life-threatening, or 
require hospitalization, but which may be considered serious by the investigator or 
Sponsor, as it may jeopardize the subject and may require medical/surgical intervention 
to prevent one of the outcomes listed above). Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, 
blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse. 
 
The following are not considered SAEs: a visit to the emergency room or other hospital 
department < 24 hours that does not result in admission (unless considered an important 
medical or life-threatening event), an elective surgery planned prior to signing consent, 
admission as per protocol for planned medical/surgical procedure, and/or routine health 
assessments requiring admission for baseline/trending of health status (e.g. routine 
colonoscopy). 
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an 
AE (e.g. mild, moderate, or severe pain); the event itself may be of minor medical 
significance (e.g. severe back pain). “Serious” is a regulatory definition, as defined above. 
Seriousness (not severity) serves as the basis for defining regulatory reporting obligations.  
Severity and seriousness should be independently assessed when recording AEs and SAEs on 
the eCRF. 
7.1.3 
Abnormal Physical Exam, Laboratory, Vital Sign, and Electrocardiogram 
Findings  
Abnormal physical exam findings that are clinically significant and are identified prior to the 
first dose of study drug should be recorded as medical history. New or worsening clinically 
significant abnormal physical exam findings identified after the first dose of study drug 
should be recorded as AEs.   
Only abnormal laboratory, vital sign, and ECG findings that are considered clinically 
significant by the investigator (e.g. require active management or are associated with 
accompanying symptoms/signs) will be recorded as medical history or AEs on the eCRF. 
Abnormal laboratory, vital sign, and ECG findings that occur prior to the first dose of study 
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drug should be recorded as medical history, and abnormal findings that occur after the first 
dose of study drug should be recorded as AEs. 
If the clinically significant laboratory, vital sign, or ECG abnormality is a sign associated 
with a confirmed disease or condition (e.g. elevated creatinine in a subject diagnosed with 
chronic kidney disease), only the diagnosis (chronic kidney disease) needs to be recorded on 
the AE eCRF (rather than listing individual test findings as AEs).  
Separate instances of the same clinically significant laboratory, vital sign, or ECG 
abnormality across visits should not be recorded as separate AEs or SAEs. 
7.1.4 
Deaths  
Any deaths that occur from the time of informed consent to the follow-up visit, regardless of 
attribution, must be reported within 24 hours of investigator’s awareness of the death. See 
Safety Form Completion Instructions for complete instructions. 
The Sponsor should be provided a copy of any post-mortem findings and/or relevant medical 
reports, including histopathology. 
7.1.5 
Pregnancies and Contraception Requirements for Females 
For the purposes of this study, a female of childbearing potential is defined as any female 
who has experienced menarche and is pre-menopausal, unless permanently surgically sterile 
(e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy). A postmenopausal 
state is defined as no menses for 12 months without an alternative medical cause in a 
previously menstruating female.  
For the purposes of this study, acceptable contraception is defined below based on 
Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals: ICH M3(R2) dated January 2010, and other available 
guidelines (“U.S. Medical Eligibility Criteria for Contraceptive Use” 2010; 
“Recommendations related to contraception and pregnancy testing in clinical trials” 2014; 
“M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals” 2010):  
All female subjects of childbearing potential must use highly effective contraception, which 
includes the use of one or more of the following acceptable methods:  
1. Surgical sterilization (e.g., bilateral tubal occlusion or ligation, hysterectomy, bilateral 
salpingectomy, bilateral oophorectomy) 
2. Total (as opposed to periodic or cyclic) abstinence from heterosexual intercourse, 
only if planned for the entire duration of the study period and consistent with the 
preferred and usual lifestyle for the subject 
3. Hormonal contraception associated with consistent inhibition of ovulation; these may 
include (but are not necessarily limited to) oral, intravaginal, implantable, injectable, 
or transdermal delivery methods  
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4. Intrauterine device/system  
5. Exclusive (sole) monogamous intercourse with a sterilized (i.e., vasectomized) or 
otherwise non-fertile (e.g., castrated) male partner; the male partner must have 
received medical assessment of the surgical success 
Progesterone-only oral contraceptives are excluded as a highly effective method of 
contraception, as they do not consistently inhibit ovulation. Male or female condoms with or 
without spermicide, and female caps, diaphragms, and sponges with spermicide, or 
combinations (double barrier) are also excluded as highly effective contraceptive methods. 
Any pregnancy occurring in a female subject or the female partner of a male subject, from 
the first study drug administration through the required follow-up visit must be reported 
within 24 hours of the investigator’s awareness of the pregnancy. See Safety Form 
Completion Instructions for complete instructions.  
The investigator will follow the pregnancy to delivery or other pregnancy outcome.  
Pregnancy in a female clinical trial subject or female partner of a male clinical trial subject is 
not an SAE per se. Complications of such pregnancies (for example, spontaneous abortion) 
may qualify as SAEs and should be reported as such even if they occur after the follow-up 
visit. Any congenital anomalies/birth defects must be recorded and reported as SAEs. See 
Safety Form Completion Instructions for complete instructions.  
7.1.6 
Worsening of Pruritus or Underlying Pruritic Skin Disease 
Pruritus or the underlying pruritic skin disease (PN, AD, or psoriasis) should be recorded as 
an AE or SAE only if considered by the investigator to have worsened in severity beyond the 
subject’s typical fluctuations. It is important to include a description of the nature of the 
unexpected worsening when recording the AE or SAE (e.g. new PN lesions in previously 
uninvolved skin). 
7.2 
Methods and Timing for Recording and Reporting Adverse Events 
7.2.1 
Adverse Event Reporting Period 
Any AE occurrence during the study must be recorded on source documentation and eCRF at 
the site, in accordance with protocol instructions.  
AEs and SAEs will be recorded from the first study drug administration through the follow-
up visit. After the 5-week follow-up visit, only SAEs that are believed to be drug-related 
should be reported. 
After informed consent, but prior to initiation of study drug, only SAEs considered by the 
investigator to be caused by a protocol-mandated intervention will be collected (e.g. SAEs 
related to invasive procedures such as blood collection). These procedure-related SAEs 
should only be reported on the source documents and SAE form, not on the AE eCRF. 
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Subjects who undergo Baseline visit procedures but are not enrolled into the study will not 
have SAEs recorded in the clinical database. 
7.2.2 
Eliciting Adverse Events 
Investigators will seek information on AEs and SAEs at each subject contact through the 
follow-up visit. All AEs and SAEs, whether reported by the subject or noted by authorized 
study personnel, will be recorded in the subject’s medical record and on the AE eCRF page, 
and, if serious, on the SAE form. For each AE and SAE recorded, the investigator will make 
an assessment of seriousness, severity, and causality. 
7.2.3 
Assessment of Severity 
All AEs entered into the eCRF will be graded for severity using the National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 (“Common 
Terminology Criteria for Adverse Events (CTCAE)” 2010) to describe the maximum 
intensity of the adverse event.   
If the AE cannot be found in the event-specific NCI CTCAE grading criteria, the investigator 
should use the definitions for Grade 1, 2, 3, and 4 in Table 1. 
 Table 1 
Adverse Event Grading 
Grade 
Severity 
Alternate Descriptiona 
1 
Mild (apply event-specific NCI 
CTCAE grading criteria) 
Asymptomatic or mild symptoms; clinical or 
diagnostic observations only; intervention not 
indicated. 
2 
Moderate (apply event-specific NCI 
CTCAE grading criteria) 
Minimal, local or noninvasive intervention 
indicated; limiting age-appropriate 
instrumental activities of daily living (ADLb) 
3 
Severe (apply event-specific NCI 
CTCAE grading criteria) 
Severe or medically significant but not 
immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; 
disabling; limiting self care ADLc 
4 
Very severe, life threatening, or 
disabling (apply event-specific NCI 
CTCAE grading criteria) 
Life-threatening consequences; urgent 
intervention indicated. 
5 
Death related to AE 
 
a 
Use these alternative definitions for Grade 1, 2, 3, and 4 events when the observed or reported AE is not in 
the NCI CTCAE listing. A semi-colon indicates ‘or’ within the alternate description of the grade. 
b 
Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
c 
Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden. 
Source: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 
 
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Note that severity, a measure of intensity, is not equivalent to seriousness, a regulatory 
definition of outcome. Regardless of severity, some AEs may meet the criteria for 
seriousness. See Section 7.1.2 for the definition of an SAE. 
If an adverse event changes in severity during the same study period (e.g., treatment period), 
only the highest severity grade will be recorded on the eCRF.  
7.2.4 
Assessment of Causality 
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious). An investigator’s causality assessment is the determination of whether there exists a 
reasonable possibility that the investigational product caused or contributed to an AE. 
Causality of an AE will be assessed by the investigator using the following terms: 
• Likely Related: A reaction that follows a reasonable temporal sequence from 
administration of the study drug; that follows a known or expected response pattern to the 
suspected study drug; and for which other potential etiologies are considered less likely 
factors than the study drug. 
• Likely Unrelated: A reaction that, considering all potential etiologies, is most likely due 
to factors other than the study drug. 
 
7.3 
Follow-up of Adverse Events and Serious Adverse Events 
The investigator must make every effort to follow all AEs and SAEs regardless of attribution 
until judged resolved or stabilized, the subject is lost to follow-up, or it has been determined 
that treatment with study drug or participation in the study is not the cause of the AE or SAE. 
7.4 
Reporting Serious Adverse Events to the Sponsor and Institutional 
Review Board (IRB) or Ethics Committee (EC)  
The Sponsor or designee is under obligation to report certain SAEs to regulatory authorities 
related to investigational drugs in clinical trials. The Sponsor or designee must be notified 
within 24 hours of an AE when the investigator determines that an AE meets the protocol 
definition of an SAE, regardless of the cause or relationship to study drug.  
An SAE related to study participation occurring before study drug administration and after 
informed consent should be promptly reported to the Sponsor. If the investigator learns of 
any SAE at any time after a participant has been discharged from the study, and the SAE is 
considered likely related to study drug, the SAE should be promptly reported to the Sponsor. 
Please see the Safety Form Report Completion Instructions for safety reporting instructions.  
The investigator must also comply with applicable requirements concerning reporting of 
SAEs to the IRB or EC. This may include initial or follow-up notification of an SAE or other 
safety information. 
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7.5 
Reporting Serious Adverse Events to Regulatory Authorities and Study 
Investigators 
The Sponsor, or its designee, is responsible for submitting reports of serious, unexpected 
related adverse events to regulatory authorities on an expedited basis, according to the ICH 
E2A Guideline and to other regulatory authorities according to national and local regulations 
as required. The Sponsor, or its designee, is responsible for prompt submission to the IRB or 
EC of any expedited SAE reports submitted to regulatory authorities. All investigators 
participating in ongoing clinical studies with serlopitant will receive copies of the SAE 
reports submitted on an expedited basis to regulatory authorities. 
8 
STATISTICAL METHODS  
All statistical processing will be performed using SAS® unless otherwise stated. No interim 
analyses are planned. Data will be summarized with descriptive statistics by visit. For 
continuous variables, the following information will be presented: n, mean, standard 
deviation, median, minimum and maximum. For categorical variables, counts and 
percentages will be used. 
Baseline will be the last recorded value prior to the start of treatment.  
A SAP describing all statistical analyses will be written as a separate document. 
8.1 
Handling of Missing Data and Excluded Therapy Use  
Summary statistics will generally be reported based upon observed data. Should a 
determination of treatment period (on treatment, pre-treatment) be required for adverse 
events or concomitant medication but the corresponding date is missing, or is a partial date, 
the event/medication will be considered on treatment unless the portions of the date that are 
available indicate this is not possible. 
8.2 
Analysis Population  
All subjects who receive at least 1 confirmed dose of study drug and have at least 1 post-
baseline safety assessment will be included in the safety population. All analyses will be 
performed using the safety population.   
8.3 
Subject Disposition  
An accounting of all subjects by disposition will be presented. Subjects who discontinue 
study drug prematurely or withdraw from the study will be summarized and listed, with a 
description of the reason for early termination/withdrawal. 
8.4 
Subject Characteristics  
Demographic and other baseline characteristics will be summarized. 
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8.5 
Concomitant Medications  
Concomitant medications will be coded by the World Health Organization Drug Dictionary 
to Anatomical Therapeutic Classification (ATC) and preferred drug name. Concomitant 
medications will be summarized by ATC level and preferred drug name and listed. 
8.6 
Treatment Compliance and Extent of Exposure  
Compliance with study drug dosing will be determined based on tablet counts recorded on 
the eCRF. Compliance will be calculated by analyzing expected number of tablets returned 
versus actual number of tablets returned. Summaries of treatment exposure will also be 
produced.  
8.7 
Efficacy Analyses  
Descriptive statistics will be used to summarize the following: 
• Change from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52  
• Change from baseline in DLQI (symptoms and feelings, daily activities, leisure, work or 
school performance, personal relationships, and treatment) to Weeks 20, 36 and 52 
• Change from baseline in IGA PN-S to Weeks 4, 8, 20, 28, 36, 44, and 52.   
 
Data will be summarized by time point using frequency tabulations or descriptive statistics as 
appropriate. Observed results, as well as change from baseline will be summarized, as 
appropriate. 
8.8 
Safety Analyses  
8.8.1 
Adverse Events  
All AEs will be classified by system organ class and preferred term using the Medical 
Dictionary for Regulatory Activities (MedDRA). TEAEs will be tabulated in a manner which 
provides information about the incidence of TEAEs for the entire treatment period as well as 
by time period in order to understand the evolution of TEAEs over time. Thus, in addition to 
the TEAE analysis over the entire 12-month treatment time, results will be presented for the 
following periods: 0 to 4 weeks, > 4 to 12 weeks, > 12 to 28 weeks, > 28 weeks to 36 weeks, 
> 36 to end of treatment, and end of treatment to end of the study (including by weekly 
periods from end of treatment to end of study). For incidence reporting, if a subject reported 
more than one TEAE that was coded to the same system organ class or preferred term, the 
subject will be counted only once for that specific system organ class or preferred term. An 
overview of AEs, which includes subject incidence of AEs, TEAEs, treatment-related 
TEAEs, TEAEs by severity, SAEs, deaths, and AEs leading to discontinuation, will be 
presented.  
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All information pertaining to AEs noted during the study will be listed by subject and will 
include a verbatim description of the event as reported by the investigator, as well as the 
preferred term, system organ class, start date, end date (if ended), seriousness, severity, 
action taken regarding the study drug, outcome, and relationship to the study drug. In 
addition, a listing of subjects who prematurely discontinue from the study due to AEs will be 
provided. 
SAEs will be listed and summarized in a similar manner to AEs. 
8.8.2 
Clinical Safety Laboratory Results  
Clinical safety laboratory values will be measured by a central laboratory. Summary statistics 
for actual values and for changes from baseline will be tabulated for laboratory results by 
scheduled visit. Graphs of laboratory values over time will also be produced, and listings will 
be provided.  
Subjects with clinical laboratory values outside of the normal reference range at any post-
baseline assessment will be summarized. Shifts from baseline laboratory values will be 
tabulated. A listing of all out-of-range laboratory test results, including assessment of clinical 
significance, will also be provided. 
8.8.3 
Vital Signs  
The observed vital sign data and change from baseline for each scheduled visit will be 
summarized with descriptive statistics, and presented in a listing.  
8.8.4 
Electrocardiograms  
The overall ECG assessment (abnormal or normal) will be summarized and descriptively 
characterized, along with a summary of how many subjects developed a post treatment 
abnormal result.  
8.8.5 
Physical Exams  
Physical exam findings will be recorded by the sites within medical history or adverse events 
and otherwise not summarized, with the exception of weight and change from baseline in 
weight. 
8.8.6 
Menstrual Diaries 
Menstrual diary dates will be used to summarize number and duration of menses.  
8.8.7 
Hospital Anxiety and Depression Scale   
The observed data and change from baseline for the HADS will be summarized with 
descriptive statistics by scheduled visit. Both the Depression and the Anxiety subscales will 
be reported. 
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8.8.8 
Epworth Sleepiness Scale   
The observed data and change from baseline for the ESS will be summarized with descriptive 
statistics by scheduled visit.  
9 
ADMINISTRATIVE ASPECTS 
9.1 
Changes to the Protocol 
Protocol amendments must be made only with the prior written approval of the Sponsor. An 
investigator signature will be obtained for the initial protocol and any amendments. 
Substantial amendments will be provided to the appropriate regulatory authorities. No 
protocol changes affecting the following will be made without the written approval of the 
Sponsor and the responsible IRB or EC: 
• Safety and/or eligibility of subjects 
• Data integrity 
• Study design or conduct 
• Willingness of a subject to participate in the study 
9.2 
Study Termination 
The Sponsor has the right to terminate this study at any time. Reasons may include, but are 
not limited to, evidence of a potential safety risk in this study or other serlopitant studies or 
poor enrollment. The study may be terminated at the request of the US Food and Drug 
Administration, the European Medicines Agency, other Competent Authorities or regulatory 
agencies with appropriate jurisdiction, or if the approval to manufacture or to import study 
drug is revoked by those with jurisdiction. A written statement fully documenting the reasons 
for study termination will be provided to the IRB or EC. 
9.3 
Monitoring and Auditing Procedures 
The Sponsor will designate study monitors who will be responsible for monitoring the 
conduct of this study. A separate study Monitoring Plan will include details regarding the 
responsibilities of the study monitors, investigator responsibilities in providing access to 
records and addressing issues identified, the frequency and structure of monitoring visits, and 
adherence to subject confidentiality as outlined in the Informed Consent Form (ICF). 
9.4 
Transfer of Obligations 
The Sponsor will delegate certain aspects of study oversight to Contract Research 
Organizations (CROs). The specific responsibilities will be detailed in Transfer of 
Obligations documents.  
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9.5 
Informed Consent 
The purpose of the study, the procedures to be carried out, and any potential risks of study 
participation will be described in non-technical terms in the ICF. After having reviewed and 
understood the ICF, subjects will be required to read, sign, and date an IRB-approved or EC-
approved consent form before any study-specific procedures are carried out. Subjects will be 
assured that they may withdraw from the study at any time without jeopardizing medical care 
related to or required as a result of study participation. The original signed consent form will 
be maintained in the investigator site file. Copies of signed consent forms will be provided to 
the subject. 
9.6 
Communication with the Institutional Review Board or Ethics Committee 
The IRB or EC is constituted and operates in accordance with the principles and 
requirements described in the ICH E6(R2) guideline. The protocol, ICF, other written subject 
information, and any proposed study advertising material must be submitted to the IRB or 
EC for written approval. IRB or EC approval of these documents will be provided to the 
investigator. The study will not start until the IRB or EC has granted its approval of the study 
materials and procedures. 
Protocol amendments will be submitted to the IRB or EC as explained in Section 9.1. SAE 
information will be submitted to the IRB or EC as explained in Section 7.4.  
If the study is terminated by the Sponsor, a written statement fully documenting the reason(s) 
for study termination will be provided to the IRB or EC. 
9.7 
Disclosure and Confidentiality 
By signing this protocol, the investigator agrees to keep all information provided by the 
Sponsor in strict confidence and to require the same confidentiality from site staff and the 
IRB or EC. Study documents provided by the Sponsor (e.g. protocol, Investigator Brochure, 
eCRFs) will be stored appropriately to ensure their confidentiality. The information provided 
by the Sponsor to the investigator may not be disclosed to others without direct written 
authorization from the Sponsor, except to the extent necessary to obtain informed consent 
from subjects who wish to participate in the study.  
The investigator must ensure that the subjects be identified by a unique subject study 
number. Other study-related documents that may contain confidential participant information 
(e.g. signed ICFs) will be kept in strict confidence by the investigator and be stored in a 
secure location with access restricted to the study staff. 
9.8 
Records and Electronic Case Report Forms 
All study data except central laboratory and ECG data will be recorded in an eCRF system. 
Data will be entered at the site by the appropriately designated and trained site personnel. All 
source documents from which eCRF entries are derived should be placed in the subject’s 
medical records. eCRFs will be completed for every subject screened in the study. The 
investigator/institution should maintain adequate and accurate source documents and trial 
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records that include all pertinent observations on each of the site’s trial subjects. Source data 
should 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 (e.g., via an audit trail). 
The study monitor will review all eCRFs in detail and will have access to participant medical 
records, laboratory data, and other source documentation to allow required eCRF fields to be 
verified by source data. 
Data consistency and plausibility checks against data entered into the eCRF will be included 
in the eCRF system. Data corrections can be performed in the eCRFs by the site. For each 
instance of data modification, the system requires a reason for change. The system keeps a 
full audit trail of the data values, the date and time of modification, and the electronic 
signature of the user who performed the change. 
After a full review of the eCRFs by the study monitor and resolution of any data 
clarifications, the investigator will review, sign, and approve the subject’s eCRF. All 
essential documents, source data, clinical records, and laboratory data will be retained by the 
site in accordance with the ICH E6(R2) guideline and the site’s data retention policies. These 
records must be available for inspection by the Sponsor, monitor, and regulatory authorities. 
Furthermore, the investigators/institutions will permit trial-related monitoring, audits, EC 
review, and inspections by a competent authority as necessary and provide direct access to 
source data/documents. 
Further detail regarding data management and eCRFs is included in the Data Management 
Plan. 
9.9 
Good Clinical Practice and Ethical Study Conduct 
The study procedures outlined in this protocol will be conducted in accordance with 
applicable ICH Guidelines, including ICH E6(R2): Good Clinical Practice. As this study is 
conducted under a US IND, the investigator will also ensure that the basic principles of 
“Good Clinical Practice”, as outlined in 21 CFR 312, subpart D, “Responsibilities of 
Sponsors and Investigators”, 21 CFR, part 50 and 21 CFR, part 56 are adhered to. 
The study procedures outlined in this protocol will also be conducted in accordance with the 
principles of the Declaration of Helsinki. 
9.10 
End of Study Notification 
The Sponsor will notify appropriate regulatory authorities and the IRB or EC within 90 days 
from the end of the clinical study. The end of the clinical study is defined as the last study 
visit for the last subject. 
9.11 
Publication of Results 
All publications (e.g. manuscripts, abstracts, oral/slide presentations, book chapters) based on 
this study or relying on data from this study must be submitted to the Sponsor for review and 
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release before submission for publication. The Sponsor is responsible for final approval of all 
publications. 
9.12 
Final Report 
A clinical trial summary report will be provided to the appropriate regulatory authorities 
within one year of the end of the clinical study. 
 
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10 
REFERENCES  
Akiyama T, Nguyen T, Curtis E, et al. A central role for spinal dorsal horn neurons that 
express neurokinin-1 receptors in chronic itch. Pain. 2015;156(7):1240-6. 
Andoh T NT, Satoh M, Kuraishi Y. Substance P induction of itch-associated response 
mediated by cutaneous NK1 tachykinin receptors in mice. J Pharmacol Exp Ther. 
1998;286(3):1140-1145. 
Booken N, Heck M, Nicolay JP, et al. Oral aprepitant in the therapy of refractory pruritus in 
erythrodermic cutaneous T-cell lymphoma. Br J Dermatol. 2011;164(3):665-67. 
Carstens EE, Akiyama T. Central mechanisms of itch. Curr Probl Dermatol. 2016;50:11-17. 
Chuquilin M, Yazan Alghalith, Fernandez KH. Neurocutaneous disease: Cutaneous 
neuroanatomy and mechanisms of itch and pain. J Am Acad Dermatol. 
2016;74:197-212.  
Common Terminology Criteria for Adverse Events (CTCAE). 4.03 ed: National Institutes of 
Health; 2010. 
Duval A, Dubertret L. Aprepitant as an antipruritic agent? N Eng J Med. 
2009;361:1415-1416. 
El-Nour H, Lundeberg L, Al-Tawil R, et al. Upregulation of the axonal growth and the 
expression of substance P and its NK1 receptor in human allergic contact dermatitis. 
Immunopharmacol Immunotoxicol. 2006;28(4):621-631. 
Emend® (aprepitant) capsule for oral use. U.S. Prescribing Information. Merck Sharp and 
Dohme Corp. Revised August 2015. 
Examples of clinical inhibitors for P450-mediated metabolisms (for concomitant use clinical 
DDI studies and/or drug labeling) (9/26/2016). U.S. Food and Drug Administration; 
2016. 
Gerber PA, Buhren BA, Cevikbas F, et al. Preliminary evidence for a role of mast cells in 
epidermal growth factor receptor inhibitor-induced pruritus. J Am Acad Dermatol. 
2010;63(1):163-165. 
Harrison S GP. Substance P. Int J Biochem. 2001;33(6):555-576. 
Hökfelt T PB, Wahren J. Substance P: A pioneer amongst neuropeptides. J Intern Med 2001; 
249:27–40. 
Ikoma A, Steinhoff M, Ständer S, et al. The neurobiology of itch. Nat Rev Neurosci. 
2006;7:535-547. 
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Lotts T, Ständer S. Research in practice: substance P antagonism in chronic pruritus. J Dtsch 
Dermatol Ges. 2014;12(7):557-559. 
Luo J, Feng J, Liu S, et al. Molecular and cellular mechanisms that initiate pain and itch. Cell 
Mol Life Sci 2015;72:3201-23. 
M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals. Food and Drug Administration; 2010. 
Recommendations related to contraception and pregnancy testing in clinical trials. Clinical 
Trial Facilitation Group; 2014. 
Santini D, Vincenzi B, Guida FM, et al. Aprepitant for management of severe pruritus related 
to biological cancer treatments: a pilot study. Lancet Oncol. 2012;13(10):1020-1024. 
Schmelz M. Itch and pain differences and commonalities. In: Schaible HG. (eds) Pain 
Control. Handbook of Experimental Pharmacology, 2015;227:285-301.   
Ständer S, Siepmann D, Herrgott I, et al. Targeting the neurokinin receptor 1 with aprepitant: 
a novel antipruritic strategy. Plos One. 2010;5(6):e10968.   
Ständer S, Weisshaar E, Raap U. Emerging drugs for the treatment of pruritus. Exp Opin 
Emerg Drugs. 2015;20:515-21. 
Steinhoff M, Bienenstock J, Schmelz M, et al. Neurophysiological, neuroimmunological, and 
neuroendocrine basis of pruritus. J Invest Dermatol. 2006;126:1705-18. 
Steinhoff MS, von Mentzer B, Geppetti P, et al. Tachykinins and their receptors: 
contributions to physiological control and the mechanisms of disease. Physiol Rev. 
2014;94(1):265-301. 
Torres T, Fernandes I, Selores M, et al. Aprepitant: Evidence of its effectiveness in patients 
with refractory pruritus continues. J Am Acad Dermatol. 2012;66(1):e14-15. 
U.S. Medical Eligibility Criteria for Contraceptive Use, 2010. Vol 20172010. 
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APPENDIX A  
SCHEDULE OF ACTIVITIES AND ASSESSMENTS 
Examination 
Base-
line1 
Week 
4 (±7 
days) 
Week 
8 (±7 
days) 
Week 
12 (±7 
days) 
Week 
20 (±7 
days) 
Week 
28 (±7 
days) 
Week 
36 (±7 
days) 
Week 
44 (±7 
days) 
Week 
52 (±7 
days) 
ETD2 
Post-drug observation: 
3 days (±1 day), and 7, 14, 
21, and 28 days (±3 days) 
after Week 52 Visit 
Post-drug 
observation: 
35 days (±3 days) 
after Week 52 Visit 
Informed consent 
X 
  
  
  
  
  
  
  
  
 
 
 
I/E criteria 
X 
  
  
  
  
  
  
  
  
 
 
  
Demographics/ 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical exam3 
X4 
X 
X 
X4 
X 
X4 
X 
X 
X4 
X4 
 
X4 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Labs5 
X1 
X 
  
X 
  
X 
  
  
X 
X 
 
X 
Urine pregnancy test6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
ECG 
X 
X 
  
  
X 
  
X 
  
X 
X 
 
X 
WI-NRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IGA PN-S (PN subjects) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
  
DLQI 
X 
  
  
  
X 
  
X 
  
X 
X 
 
 
HADS, ESS 
X 
 
 
 
X 
 
X 
 
X 
X 
X 
X 
Photographs (if applicable) 
X 
  
  
  
X 
  
X 
  
X 
X 
 
 
Dispense/review menstrual 
diary (if applicable) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense/collect 
serlopitant 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Review study drug 
compliance  
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs/SAEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1 
Baseline may coincide with the final visit of prior applicable study; Baseline labs do not need to be repeated if completed within prior 14 days 
2 
Early Treatment Discontinuation 
3 
Baseline physical exam is complete; all other physical exams are targeted 
4 
Height/weight at Baseline and weight at Weeks 12, 28, 52 and ETD/post-drug observation 35 days after Week 52  
5 
Labs are ideally performed in the morning, particularly at visits with endocrine assessments (Baseline, Weeks 12, 28 and 52).  Hematology and Chemistry at Baseline, 
Weeks 4, 12, 28, 52, and ETD/ post-drug observation 35 days after Week 52; Reproductive Endocrinology at Baseline, Weeks 28 and 52 (females under 55 years of age 
at consent) 
6 
For females of childbearing potential (with positive or equivocal results to be confirmed by a serum pregnancy test). Monthly pregnancy testing can be performed in 
between visits (and recorded as an Unscheduled visit), and at any time per the investigator’s discretion. 
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APPENDIX B  
LIST OF STRONG CYP3A4 INHIBITORS   
The list of strong CYP3A4 inhibitors is based on the United States Food and Drug 
Administration (FDA) list effective September 26, 2016, Examples of clinical inhibitors for 
P450-mediated metabolisms (for concomitant use clinical DDI studies and/or drug labeling 
(“Examples of clinical inhibitors for P450-mediated metabolisms (for concomitant use clinical 
DDI studies and/or drug labeling (9/26/2016)”).  
Note: This Appendix may be replaced if applicable (e.g., if updated by the FDA) through site 
communications without requiring a protocol amendment. 
1. 
boceprevir 
2. 
clarithromycin 
3. 
cobicistat 
4. 
conivaptan 
5. 
danoprevir and ritonavir 
6. 
diltiazem 
7. 
elvitegravir and ritonavir 
8. 
idelalisib 
9. 
indinavir and ritonavir 
10. 
itraconazolea 
11. 
ketoconazolea 
12. 
lopinavir and ritonavir 
13. 
nefazodone 
14. 
nelfinavir 
15. 
paritaprevir and ritonavir and (ombitasvir and/or dasabuvir) 
16. 
posaconazolea 
17. 
ritonavir 
18. 
saquinavir and ritonavir 
19. 
telaprevir 
20. 
tipranavir and ritonavir 
21. 
troleandomycin 
22. 
voriconazolea 
23. 
regular grapefruit juice consumption (note: The effect of grapefruit juice varies 
widely among brands and is concentration-, dose-, and preparation-dependent. 
Grapefruit juice may be a strong or a moderate CYP3A inhibitor depending on the 
preparation)b 
 
a 
When administered topically, it may not be considered a strong CYP3A4 inhibitor due to limited systemic 
absorption. 
b 
The occasional consumption of grapefruit juice or the consumption of grapefruit or other citrus fruits (e.g., 
pomelo, lemon, lime, Seville orange, bitter orange, starfruit) is not contraindicated. 
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APPENDIX C  
WORST ITCH NUMERIC RATING SCALE QUESTIONNAIRE 
c 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
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APPENDIX D 
INVESTIGATOR’S GLOBAL ASSESSMENT OF PRURIGO 
NODULARIS: STAGE 
Score 
Category 
Description: Stage (IGA PN-S) 
0 
Clear 
No nodules (0 nodules) 
1 
Almost 
Clear 
Rare, flattened lesions, with no more than 5 dome-shaped palpable nodules 
(approximately 1-5 nodules) 
2 
Mild 
Few, mostly flattened lesions, with small number of dome-shaped palpable 
nodules (approximately 6-19 nodules) 
3 
Moderate 
Many lesions, partially flattened, and dome-shaped palpable nodules 
(approximately 20-100 nodules) 
4 
Severe 
Abundant lesions, majority are dome-shaped palpable nodules (over 
100 nodules) 
 
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APPENDIX E 
DERMATOLOGY LIFE QUALITY INDEX 
Different language versions may be used. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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APPENDIX F 
HOSPITAL ANXIETY AND DEPRESSION SCALE 
 
 
To be used under license. 
  
 
 
  
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
  
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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APPENDIX G 
EPWORTH SLEEPINESS SCALE 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
   
 
  
  
 
  
 
  
   
 
 
 
 
  
 
 
  
  
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
155


 
1 
CLINICAL STUDY PROTOCOL MTI-107 
SUMMARY OF CHANGES 
 
Drug Product Name: 
Serlopitant 
 
Study Title:  
AN OPEN-LABEL LONG-TERM SAFETY STUDY OF 
SERLOPITANT FOR THE TREATMENT OF PRURITUS 
IND No.: 
 
 
117780 
EudraCT No.:  
 
2017-004211-40 
ClinicalTrials.gov ID:  
NCT03540160 
Protocol Version: 
 
2.0 
Protocol Date: 
 
03 July 2018 
Replaces Version/Date: 
1.1 / 11 April 2018 
 
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The following changes were made to the MTI-107 Clinical Study Protocol from Version 1.1 to Version 2.0. 
KEY CHANGES: 
Section(s) 
Summary of Change 
Reason for Change 
Protocol Synopsis  
Updated consistent with changes to the protocol body. 
Ensure consistency between synopsis and protocol 
body.  
1.2.3 Serlopitant in 
Pruritus-Related 
Studies 
Amended to include language regarding the potential 
benefit and potential risk for the participating patients as 
well as the assessment of the ratio of this benefit and risk. 
Clarifies the potential benefit and risk for the 
participating patients.  
3.1 Overall Study 
Design, 6.5 Study 
Visits  
The study post-drug observation period is extended to 
5 weeks from 4 weeks. 
Allows for the final Post-Drug Observation visit to 
occur after five terminal elimination half-lives of 
M2/M2a serlopitant metabolite. 
3.3.2 Efficacy 
Endpoints, 6.1.3 
PROMIS Itch 
Questionnaire, 6.5 
Study Visits, 8.7 
Efficacy Analyses 
Removal of the PROMIS-PIQ associated efficacy 
endpoints and analyses. Deleted section 6.1.3 and removed 
PROMIS-PIQ assessments at visits. 
 
The PROMIS-PIQ is not yet validated as a quality of 
life instrument, thus, this assessment has been removed 
from the study protocol. 
3.3.1 Safety 
Endpoints, 6.2 
Safety Parameters 
Added two safety endpoints to measure change from 
baseline in Hospital Anxiety and Depression Scale 
(HADS) and the Epworth Sleepiness Scale (ESS) 
responses. 
 
 
Safety assessments to evaluate presence and severity of 
anxiety, depression, and daytime sleepiness while on 
study drug and during the follow-up period. Evaluation 
during the follow-up period is intended to support 
analysis of the study drug’s potential for physical 
dependence. 
4.2 Inclusion 
Criteria 
Clarified that for IE criteria #2, participants from TCP-102 
study coming into this study or those that have not 
participated in a prior serlopitant study would need to have 
WI-NRS score ≥7 in the 24-hour period prior to the 
Baseline visit. 
 
Defines eligibility criteria with greater specificity. 
4.3 Exclusion 
Criteria 
Revised exclusion criterion #2 to identify exclusionary 
psychiatric diagnoses, without requiring reference to 
DSM-5 manual. 
Defines eligibility criteria with greater specificity. 
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Section(s) 
Summary of Change 
Reason for Change 
Revised exclusion criterion #3 to exclude patients with 
untreated or inadequately treated adrenal or pituitary 
nodules or disease in addition to untreated or inadequately 
treated thyroid disease, and history of thyroid malignancy. 
 
5.3. Dosing 
Regimen 
Study drug may be taken with or without food. 
Recent clinical study data has demonstrated that the 
previous requirement to avoid food for two hours 
around dosing with serlopitant is unnecessary. 
5.6 Study Drug 
Discontinuation 
Revised statement regarding pregnancy to “A female 
subject desires to become pregnant at the current time, 
stops contraception or expels her intrauterine 
device/implant or becomes pregnant”, added requirement 
for study drug discontinuation if “A female subject has 
new breast findings (e.g. a palpable mass or abnormal 
mammography, discharge), or has abnormal vaginal 
discharge or bleeding”. Revised statement regarding the 
best interests of the subject to “Discontinuation is deemed 
to be in the best interest of the subject, in the investigator’s 
and/or Sponsor’s opinion, including evidence that the 
subject does not meet inclusion/exclusion criteria intended 
primarily for safety reasons, or a persistent lack of 
adherence to study procedures”. Revised statement 
regarding  medical conditions that may jeopardize the 
subject’s safety to “Any medical condition that may 
jeopardize the subject’s safety if study drug is continued, 
in the investigator’s and/or Sponsor’s opinion; this may 
include the development of persistently (2 successive 
occasions) abnormal thyroid function tests (TSH >10, or 
TSH > 6 with low free T4; TSH <0.1, or TSH < 0.35 with 
high free T4); abnormal morning prolactin, cortisol, or 
corticotropin levels; or signs and symptoms of adrenal 
insufficiency”. 
Clarification of requirements for study drug 
discontinuation.  
 
 
6.1.1 Itch Numeric 
Rating Scale; 6.1.2 
Noted assessment instruments were provided as 
Appendices. 
Clarification only. 
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Section(s) 
Summary of Change 
Reason for Change 
and 6.1.3 
Investigator’s 
Global 
Assessments; 
6.1.4 DLQI 
 
 
6.2.2 Physical 
Examination 
Specified that female subjects with targeted breast 
examinations should have these performed after blood 
draw for clinical laboratory tests.   
Clarification only. 
6.2.3 Clinical 
Laboratory 
Assessments 
Provided instruction on timeframe for laboratory 
collection, added Endocrine panel, added standard 
cosyntropin stimulation testing for subjects with low 
cortisol level.  
Clarified that pregnancy testing can be performed in 
between visits and at any time per the investigator’s 
discretion and as required by local authorities.  
Added optional studies for etiology of PN for participants 
from TCP-102 study or those that had not participated in a 
prior clinical study of serlopitant that would be supported 
through local lab. 
Specified endocrinologic laboratory assessments. 
 
 
 
Clarification only. 
 
 
Support evaluation of underlying disease for subjects 
with PN for those who did not participate in studies 
MTI-105 or MTI-106. 
6.2.7 Assessment of 
Potential for 
Physical 
Dependence 
Provided additional details regarding the assessment of 
potential for physical dependence via frequent 
administration of HADS and ESS questionnaires, vital 
signs, ECG and lab analyses and medical review of all 
TEAEs reported during this time period. 
Specified comprehensive evaluations for physical 
dependence and withdrawal of study drug.  
 
6.4. Study Visits 
Added the requirement for completion of menstrual diaries 
for female subjects throughout the study. 
Updated list of procedures for each visit, added additional 
post-drug observation visits.  
Specified request to obtain menstrual data. 
 
Clarifications to align with other protocol revisions. 
7.1.5 Pregnancies 
and Contraception 
Requirement for 
Females 
Clarification of contraceptive requirements including need 
for highly effective contraception until 5 weeks after last 
dose of study drug. 
Revised section to better align with the 
“Recommendations related to contraception and 
pregnancy testing in clinical trials” from the Clinical 
Trial Facilitation Group (2014). 
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Section(s) 
Summary of Change 
Reason for Change 
8.8. Safety Analyses Added weekly analyses of TEAEs during the post-drug 
observation period. Added HADS and ESS analyses. 
Added analysis for menstrual diaries. 
Supports comprehensive evaluations for physical 
dependence and withdrawal of study drug.  
Additional analysis, may correlate with other safety 
data. 
9.2 Study 
Termination 
Added statement that the study may be terminated at the 
request of the US food and Drug Administration, the 
European Medicines Agency, other Competent Authorities 
or regulatory agencies with appropriate jurisdiction, or if 
the approval to manufacture or to import study drug is 
revoked by those with jurisdiction. 
Clarified termination language to include relevant 
agencies in Europe and USA.  
 
ADMINISTRATIVE CHANGES: 
Section(s) 
Summary of Change 
Title page 
Added protocol version number and release date, added Clinical Trials.gov ID number 
Signature Page for Investigator(s)   
Added protocol version number and release date, added Clinical Trials.gov ID number 
Sponsor Protocol Approval Signature(s) 
Added protocol version number, added Clinical Trials.gov ID number 
Table of Contents 
Updated  
List of Abbreviations and Definitions of 
Terms 
Updated for consistency with protocol 
Appendix A  
Updated tables for consistency with protocol  
Appendix B 
Updated for consistency with protocol 
Appendix C 
Added the WI-NRS questionnaire 
Appendix D 
Added Investigator’s Global Assessment of PN Stage scale 
Appendix E 
Added DLQI 
Appendix F 
Added Hospital Anxiety and Depression Scale 
Appendix G 
Added Epworth Sleepiness Scale 
Throughout  
Updated protocol version in footer; Edited formatting and corrected minor typos and 
inconsistencies 
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Serlopitant 
 
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MTI-107 Protocol, Summary of Changes Version 1.1 to Version 2.0 
 
 
 
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CLINICAL STUDY PROTOCOL 
 
TITLE:  
AN OPEN-LABEL LONG-TERM SAFETY STUDY OF 
SERLOPITANT FOR THE TREATMENT OF PRURITUS  
IND No.: 
 
 
117780 
EudraCT: 
 
 
2017-004211-40 
ClinicalTrials.gov ID:  
NCT03540160 
Protocol No.:  
 
MTI-107 
Protocol Version/Date: 
Version 3.0/21 March 2019 
Development Phase:  
Phase 3 
Sponsor: 
 
 
Menlo Therapeutics Inc. 
200 Cardinal Way, 2nd Floor 
Redwood City, CA 94063, USA 
 
 
 
Confidentiality Statement: 
This document is a confidential communication of Menlo Therapeutics Inc. As such, the 
recipients agree not to disclose or reproduce, without prior written approval, this 
document and any attachments, except to appropriate Institutional Review Boards, Ethics 
Committees, representatives of the US Food and Drug Administration, the European 
Medicines Agency, other Competent Authorities or regulatory agencies, or as otherwise 
required by applicable laws or regulations. 
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SIGNATURE PAGE FOR INVESTIGATOR(S) 
 
TITLE:  
AN OPEN-LABEL LONG-TERM SAFETY STUDY OF 
SERLOPITANT FOR THE TREATMENT OF PRURITUS 
IND No.: 
 
 
117780 
EudraCT: 
 
 
2017-004211-40 
ClinicalTrials.gov ID:  
NCT03540160 
Protocol No.:  
 
MTI-107 
Protocol Version/Date: 
Version 3.0/21 March 2019   
Development Phase:  
Phase 3 
Sponsor: 
 
 
Menlo Therapeutics Inc. 
200 Cardinal Way, 2nd Floor 
Redwood City, CA 94063, USA 
 
 
I have read the protocol and agree to conduct this study in accordance with the protocol, all 
relevant laws and regulations in force at the time, International Conference on Harmonisation 
Guidelines for Good Clinical Practice, and the Declaration of Helsinki.  
 
 
 
Principal Investigator’s printed name 
 
 
 
 
 
 
Principal Investigator’s signature 
 
Date (DD-MMM-YYYY) 
 
  
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PROTOCOL SYNOPSIS 
Study Title: 
An Open-Label Long-Term Safety Study of Serlopitant for the Treatment of Pruritus  
Protocol Number: 
MTI-107 
Sponsor: 
Menlo Therapeutics Inc. 
Development Phase: 
Phase 3 
Study Objectives: 
Primary objective:  
 
To assess the long-term safety of serlopitant in adults with pruritus 
associated with prurigo nodularis (PN), atopic dermatitis (AD), or psoriasis. 
Secondary objectives:  
 
To assess change in severity of pruritus in subjects with PN, AD, or 
psoriasis using the worst-itch numeric rating scale (WI-NRS).  
 
To assess change in severity and extent of PN using the Investigator’s 
Global Assessment of PN Stage (IGA PN-S), for those subjects with PN. 
 
To assess whether serlopitant produces physical dependence.  
Study Design: 
Study MTI-107 is a multicenter, open-label study to assess the long-term safety of 
serlopitant in adults with pruritus associated with PN, AD, or psoriasis. Eligible 
subjects who have completed selected studies of serlopitant may be given the 
opportunity, at the investigator’s discretion, to consent to and participate in this 
open-label study, regardless of their treatment allocation in prior studies. If deemed 
necessary by Menlo Therapeutics to meet enrollment objectives, eligible subjects 
who have not participated in a prior serlopitant study may also be enrolled in study 
MTI-107. 
The study will consist of two periods, for a total study period of approximately 
57 weeks: 
 
Treatment period: 52 weeks 
 
Post-drug observation period: 5 weeks 
During the treatment period, subjects will take one serlopitant 5 mg tablet once daily 
orally.  
Standard therapy for the concurrent skin lesions and pruritus may be employed 
during this study.  
After completion of the 52-week treatment period, all subjects will enter a 5-week 
post-drug observation period. Subjects who discontinue treatment early will have 
post-drug observation visits through 5 weeks after their last dose of serlopitant.  
Safety Review: 
An internal safety monitoring team consisting of representatives from Menlo 
Therapeutics Inc. and its designees will monitor safety data on a regular basis 
throughout the study. 
Planned Sample Size: 
Up to 700 subjects  
Study Population: 
The study will enroll adults with pruritus associated with PN, AD, or psoriasis. 
Inclusion Criteria (Subjects must meet the following criteria to be enrolled into the 
study):  
1. Male or female, age 18 years or older at consent. 
2. Subject reports pruritus in the 24-hour period prior to enrollment and: 
a. 
Has completed a prior applicable clinical study of serlopitant 
without a serious adverse event (SAE) that was assessed as likely 
related to the study drug. (For participants from study TCP-102, 
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the WI-NRS score must be ≥ 7 in the 24-hour period prior to the 
Baseline visit.) 
OR  
b. Has not participated in a prior clinical study of serlopitant and has 
a clinical diagnosis of PN, AD, or psoriasis, and has a WI-NRS 
score ≥ 7 in the 24-hour period prior to the Baseline visit, and 
Sponsor has approved enrollment. 
3. All female subjects who are of childbearing potential must be willing to 
practice highly effective contraception (i.e., pregnancy prevention method 
with a failure rate of <1% per year) from the time of the Baseline visit until 
5 weeks after last dose of study drug. 
4. Willing and able (has adequate cognitive ability, in the investigator’s 
opinion) to comply with study visits and study related requirements 
including providing written informed consent. 
 
Exclusion Criteria (Subjects who meet any of the following criteria are not eligible 
for participation in the study): 
1. Presence of malignancy within 5 years prior to enrollment (exception for 
non-melanoma cutaneous malignancies). 
2. Any known major psychiatric diagnosis, such as major depressive disorder, 
bipolar disorder, schizophrenia, psychotic disorder, intellectual disability, 
severe alcohol use disorder, which may confound the assessment of 
serlopitant safety or efficacy, or interfere with the subject’s ability to 
comply with protocol-mandated activities, within 3 years prior to 
enrollment.   
3. Untreated or inadequately treated thyroid, adrenal, or pituitary nodules or 
disease, or history of thyroid malignancy; or the presence of any medical 
condition or disability, that, in the investigator’s opinion, could interfere 
with the assessment of safety in this study or compromise the safety of the 
subject.  
4. Treatment with any investigational therapy within 4 weeks or 5-half-lives 
prior to enrollment (whichever is longer) or expected participation in 
another clinical study involving an investigational product or device during 
the subject’s participation in MTI-107. 
5. Treatment with other neurokinin-1 receptor (NK1-R) antagonists (e.g., 
aprepitant, fosaprepitant, rolapitant) within 4 weeks prior to enrollment. 
6. Treatment with strong cytochrome P450 3A4 inhibitors within 4 weeks 
prior to enrollment. 
7. Currently pregnant or breastfeeding or planning to become pregnant during 
the study. 
Study Drug: 
Serlopitant 5 mg tablets 
Dosage:  
Serlopitant: 5 mg once daily orally for 52 weeks  
Safety Endpoints: 
 
Incidence of treatment-emergent adverse events (TEAEs) and SAEs 
 
Change from baseline in clinical laboratory parameters following study 
drug exposure 
 
Change from baseline in vital sign and electrocardiogram (ECG) 
parameters following study drug exposure 
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 
Change from baseline in the Hospital Anxiety and Depression Scale 
(HADS)  
 
Change from baseline in the Epworth Sleepiness Scale (ESS) 
 
Assessment of physical dependence following chronic study drug exposure, 
in the monitored 5-week post-drug discontinuation period  
Efficacy Endpoints: 
 
Change from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52  
 
Change from baseline in Dermatology Life Quality Index (DLQI) 
(symptoms and feelings, daily activities, leisure, work or school 
performance, personal relationships, and treatment) to Weeks 20, 36 and 52 
 
Change from baseline in IGA PN-S to Weeks 4, 8, 20, 28, 36, 44, and 52 
Statistical Methods: 
All subjects who receive at least 1 confirmed dose of study drug and have at least 1 
post-baseline safety assessment will be included in the safety population. All 
analyses will be performed using the safety population. 
Data will be summarized with descriptive statistics by visit. For continuous 
variables, the following information will be presented: n, mean, standard deviation, 
median, minimum and maximum. For categorical variables, counts and percentages 
will be used. 
All adverse events (AEs) will be classified by system organ class and preferred term 
using the Medical Dictionary for Regulatory Activities (MedDRA). TEAEs will be 
tabulated in a manner which provides information about the incidence of TEAEs for 
the entire treatment period as well as by specified time periods in order to 
understand the evolution of TEAEs over time. An overview of AEs, which includes 
subject incidence of TEAEs, treatment-related TEAEs, TEAEs by severity, SAEs, 
deaths, and AEs leading to discontinuation, will be presented.  
Summary statistics for actual safety laboratory values and for changes from baseline 
will be tabulated by scheduled visit. Subjects with clinical laboratory values outside 
of the normal reference range at any post-baseline assessment will be summarized. 
Shifts from baseline laboratory values will be tabulated. A listing of all out-of-range 
laboratory test results, including assessment of clinical significance will also be 
provided. 
The observed vital sign data and change from baseline will be summarized with 
descriptive statistics and presented in a listing. 
The overall ECG assessment (abnormal or normal) will be summarized and 
descriptively characterized, along with a summary of how many subjects developed 
a post treatment abnormal result.  
Physical exam findings will be recorded by the sites within medical history or AEs 
and otherwise not summarized, with the exception of weight, and change from 
baseline in weight. 
The WI-NRS, DLQI, and IGA PN-S will be summarized with descriptive statistics 
by visit. 
Summary statistics for the HADS and ESS actual values and change from baseline 
will be presented by scheduled visit. 
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Study Sites: 
Approximately 120 study sites 
Expected Duration of 
Subject’s 
Participation 
Approximately 57 weeks: 52 weeks of treatment, and a post-drug observation period 
of 5 weeks. 
 
This study will be conducted in accordance with the Guidelines of Good Clinical Practice. 
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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ............................................................................................1 
SIGNATURE PAGE FOR INVESTIGATOR(S) .....................................................................2 
SPONSOR PROTOCOL APPROVAL SIGNATURE(S) .........................................................3 
PROTOCOL SYNOPSIS...........................................................................................................4 
TABLE OF CONTENTS ...........................................................................................................8 
LIST OF APPENDICES ..........................................................................................................11 
LIST OF TABLES ...................................................................................................................11 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..........................................12 
1 
INTRODUCTION .................................................................................................13 
1.1 
Pruritus .............................................................................................................13 
1.1.1 
Role of Substance P and the Neurokinin-1 Receptor in Pruritus .........13 
1.2 
Serlopitant ........................................................................................................14 
1.2.1 
Serlopitant Background and Nonclinical Summary ............................14 
1.2.2 
Serlopitant Clinical Summary ..............................................................15 
1.2.3 
Serlopitant in Pruritus-Related Studies ................................................15 
2 
STUDY OBJECTIVES ..........................................................................................17 
3 
STUDY DESIGN...................................................................................................17 
3.1 
Overall Study Design .......................................................................................17 
3.2 
Rationale for Study Design and Dose Selection ..............................................18 
3.3 
Study Endpoints ...............................................................................................18 
3.3.1 
Safety Endpoints ..................................................................................18 
3.3.2 
Efficacy Endpoints ...............................................................................18 
3.4 
Safety Review ..................................................................................................19 
3.4.1 
Safety Monitoring Team ......................................................................19 
4 
SELECTION OF STUDY POPULATION ...........................................................19 
4.1 
Study Population ..............................................................................................19 
4.2 
Inclusion Criteria .............................................................................................19 
4.3 
Exclusion Criteria ............................................................................................20 
5 
STUDY DRUG ......................................................................................................20 
5.1 
Study Drug Supply, Route of Administration, and Storage.............................20 
5.2 
Labeling and Study Drug Accountability ........................................................21 
5.3 
Dosing Regimen...............................................................................................21 
5.4 
Dose Modification ...........................................................................................21 
5.5 
Missed or Delayed Doses.................................................................................21 
5.6 
Study Drug Discontinuation ............................................................................21 
5.7 
Concomitant and Excluded Therapies .............................................................22 
5.7.1 
Excluded Therapies ..............................................................................22 
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5.8 
Assignment to Treatment .................................................................................23 
5.9 
Treatment Compliance .....................................................................................23 
6 
STUDY SCHEDULE AND ASSESSMENTS ......................................................23 
6.1 
Efficacy Parameters .........................................................................................23 
6.1.1 
Itch Numeric Rating Scale ...................................................................23 
6.1.2 
Investigator’s Global Assessment of PN Stage ...................................23 
6.1.3 
Dermatology Life Quality Index ..........................................................23 
6.1.4 
Photographs..........................................................................................24 
6.2 
Safety Parameters .............................................................................................24 
6.2.1 
Vital Signs ............................................................................................24 
6.2.2 
Physical Examination...........................................................................24 
6.2.3 
Clinical Laboratory Assessments .........................................................24 
6.2.4 
Electrocardiogram ................................................................................25 
6.2.5 
Hospital Anxiety and Depression Scale ...............................................25 
6.2.6 
Epworth Sleepiness Scale ....................................................................26 
6.2.7 
Assessment of Potential for Physical Dependence ..............................26 
6.3 
Subject Flow Diagram .....................................................................................26 
6.4 
Study Visits ......................................................................................................26 
6.4.1 
Baseline Visit .......................................................................................26 
6.4.2 
Week 4 Visit ........................................................................................28 
6.4.3 
Week 8 Visit ........................................................................................28 
6.4.4 
Week 12 Visit ......................................................................................29 
6.4.5 
Week 20 Visit ......................................................................................30 
6.4.6 
Week 28 Visit ......................................................................................31 
6.4.7 
Week 36 Visit ......................................................................................32 
6.4.8 
Week 44 Visit ......................................................................................32 
6.4.9 
Week 52 Visit ......................................................................................33 
6.4.10 
Early Treatment Discontinuation Visit ................................................34 
6.4.11 
Post-Drug Observation Visits ..............................................................35 
6.4.12 
Early Termination ................................................................................36 
7 
ASSESSMENT OF SAFETY ................................................................................36 
7.1 
Definitions........................................................................................................36 
7.1.1 
Adverse Event ......................................................................................36 
7.1.2 
Serious Adverse Event .........................................................................36 
7.1.3 
Abnormal Physical Exam, Laboratory, Vital Sign, and 
Electrocardiogram Findings .................................................................37 
7.1.4 
Deaths ..................................................................................................38 
7.1.5 
Pregnancies and Contraception Requirements for Females .................38 
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7.1.6 
Worsening of Pruritus or Underlying Pruritic Skin Disease ................39 
7.2 
Methods and Timing for Recording and Reporting Adverse Events ...............39 
7.2.1 
Adverse Event Reporting Period .........................................................39 
7.2.2 
Eliciting Adverse Events ......................................................................40 
7.2.3 
Assessment of Severity ........................................................................40 
7.2.4 
Assessment of Causality ......................................................................41 
7.3 
Follow-up of Adverse Events and Serious Adverse Events ............................41 
7.4 
Reporting Serious Adverse Events to the Sponsor and Institutional Review 
Board (IRB) or Ethics Committee (EC) ...........................................................41 
7.5 
Reporting Serious Adverse Events to Regulatory Authorities and Study 
Investigators .....................................................................................................42 
8 
STATISTICAL METHODS ..................................................................................42 
8.1 
Handling of Missing Data and Excluded Therapy Use ...................................42 
8.2 
Analysis Population .........................................................................................42 
8.3 
Subject Disposition ..........................................................................................42 
8.4 
Subject Characteristics .....................................................................................42 
8.5 
Concomitant Medications ................................................................................43 
8.6 
Treatment Compliance and Extent of Exposure ..............................................43 
8.7 
Efficacy Analyses ............................................................................................43 
8.8 
Safety Analyses ................................................................................................43 
8.8.1 
Adverse Events ....................................................................................43 
8.8.2 
Clinical Safety Laboratory Results ......................................................44 
8.8.3 
Vital Signs ............................................................................................44 
8.8.4 
Electrocardiograms ..............................................................................44 
8.8.5 
Physical Exams ....................................................................................44 
8.8.6 
Menstrual Diaries .................................................................................44 
8.8.7 
Hospital Anxiety and Depression Scale ...............................................44 
8.8.8 
Epworth Sleepiness Scale ....................................................................45 
9 
ADMINISTRATIVE ASPECTS ...........................................................................45 
9.1 
Changes to the Protocol ...................................................................................45 
9.2 
Study Termination ...........................................................................................45 
9.3 
Monitoring and Auditing Procedures...............................................................45 
9.4 
Transfer of Obligations ....................................................................................45 
9.5 
Informed Consent.............................................................................................46 
9.6 
Communication with the Institutional Review Board or Ethics Committee ...46 
9.7 
Disclosure and Confidentiality ........................................................................46 
9.8 
Records and Electronic Case Report Forms ....................................................46 
9.9 
Good Clinical Practice and Ethical Study Conduct .........................................47 
9.10 
End of Study Notification ................................................................................47 
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9.11 
Publication of Results ......................................................................................47 
9.12 
Final Report .....................................................................................................48 
10 
REFERENCES ......................................................................................................49 
 
LIST OF APPENDICES 
Appendix A   Schedule of Activities and Assessments ..........................................................51 
Appendix B   List of Strong CYP3A4 Inhibitors ...................................................................52 
Appendix C   Worst Itch Numeric Rating Scale Questionnaire .............................................53 
Appendix D 
Investigator’s Global Assessment of Prurigo Nodularis: Stage .......................54 
Appendix E 
Dermatology Life Quality Index ......................................................................55 
Appendix F 
Hospital Anxiety and Depression Scale ...........................................................56 
Appendix G   Epworth Sleepiness Scale ................................................................................57 
 
LIST OF TABLES 
Table 1 
Adverse Event Grading ..............................................................................40 
  
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS   
Abbreviation 
Definition 
ACTH 
Adrenocorticotropic hormone, corticotropin 
AD 
Atopic dermatitis  
ADL 
Activities of daily living 
AE 
Adverse event 
ALT 
Alanine aminotransferase  
AMH 
Anti-Mullerian hormone 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Classification 
CYP3A4 
Cytochrome P-450 3A4  
DLQI 
Dermatology Life Quality Index 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
ESS 
Epworth Sleepiness Scale 
ETD 
Early Treatment Discontinuation 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
FSH 
Follicle-stimulating hormone 
HADS 
Hospital Anxiety and Depression Scale 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IGA PN-S 
Investigator’s Global Assessment of Prurigo Nodularis Stage 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System  
LDH 
Lactate dehydrogenase 
LH 
Luteinizing hormone 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NK1-R 
Neurokinin-1 receptor 
NRS 
Numeric rating scale  
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PN 
Prurigo nodularis 
QOL 
Quality of life 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan  
SP 
Substance P 
TEAE 
Treatment-emergent adverse event 
TSH 
Thyroid stimulating hormone 
VAS 
Visual Analog Scale 
WI-NRS 
Worst-Itch Numeric Rating Scale 
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1 
INTRODUCTION 
1.1 
Pruritus  
Pruritus, or itch, is defined as an unpleasant sensation that evokes a desire to scratch 
(Ikoma 2006). Itch and pain, although closely related, are distinct sensations: itch elicits a 
scratching response, whereas pain causes a withdrawal response.  
Emerging research in neurobiology has greatly expanded the understanding of pruritus 
signaling. Pruritoceptors (itch-sensory nerve fibers) consist of two distinct classes of nerve 
fibers: histamine-responsive mechanoinsensitive C-fibers, and histamine-unresponsive 
mechanosensitive polymodal C and A fibers that are activated by cowhage (highly pruritic 
spicules from the pods of the cowhage plant Mucuna pruriens) (Schmelz 2015). The second 
class of histamine-unresponsive, cowhage-responsive nerve fibers has been of particular 
interest in pruritus research, as C-fibers that have a strong and sustained response to 
histamine comprise only about 20% of the overall mechanoinsensitive C-fiber population 
(Steinhoff 2006), and a significant proportion of chronic pruritic conditions do not appear to 
involve histamine-mediated pruritus signaling (Ikoma 2006). Substance P (SP) is a prominent 
pruritogen (itch mediator) in this histamine-independent pruritus pathway (Chuquilin 2016).  
Pruritus stimuli in the skin are transmitted via sensory neurons that have their cell bodies in 
the dorsal root ganglia (DRG) and are linked to second-order neurons in the spine 
(Carstens 2016, Luo 2015). Following activation of these DRG sensory neurons, the pruritus 
signal is transmitted to the second-order spinal neurons primarily by SP, gastrin-releasing 
peptide, and glutamate in histamine-independent pruritus, and primarily by glutamate in 
histamine-mediated pruritus (Chuquilin 2016). 
Spinal itch neuron projections ascend via the contralateral spinothalamic tract to the thalamus 
and via the lateral spinoparabrachial tract to the lateral parabrachial nucleus, from which 
point they activate multiple centers in the somatosensory cortex, the premotor cortex, and the 
cingulate cortex – areas involved in the sensory processing and motor response (scratching) 
to the itch signal (Carstens 2016, Chuquilin 2016). 
1.1.1 
Role of Substance P and the Neurokinin-1 Receptor in Pruritus 
Substance P is an undecapeptide that belongs to the tachykinin family of neuropeptides, a 
group that also includes neurokinin A and neurokinin B (Hökfelt 2001). SP has been 
implicated in a number of biological functions, both physiological and pathophysiological, 
including pruritus perception, vomiting reflex, pain perception, and immunomodulatory 
responses (Lotts 2014, Andoh 1998, Steinhoff 2014).  The biological actions of SP are 
mediated by tachykinin receptors, which consist of seven hydrophobic transmembrane 
domains coupled to G-proteins. Three tachykinin receptors have been identified: the 
neurokinin-1 (NK1-R), neurokinin-2, and neurokinin-3 receptors (Harrison 2001). The 
neurokinin-1 receptor, in particular, has been studied in great detail. NK1-R is the primary 
receptor for SP in the human body, and is found on multiple cell types, including central and 
peripheral neurons, keratinocytes, mast cells, and dendritic cells (El-Nour 2006, 
Ständer 2015).  
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NK1-R stimulation has been shown to be an important pathway for pruritus perception 
(Ständer 2015). Inhibition of this pathway results in decreased pruritus and scratching 
reflexes in animal models (Akiyama 2015). Preceding the development of serlopitant for 
pruritus-related conditions, a commercially available NK1-R antagonist (Emend USPI) has 
been used as a therapy to decrease pruritus in patients with chronic pruritus due to etiologies 
such as cutaneous T-cell lymphoma (Duval 2009, Torres 2012, Booken 2011) and erlotinib-
induced pruritus (Santini 2012, Gerber 2010). Additionally, in a study of 20 patients with 
chronic pruritus of various etiologies treated with aprepitant, 16/20 patients (80%) 
experienced a considerable reduction of itch intensity (Ständer 2010).  
1.2 
Serlopitant  
1.2.1 
Serlopitant Background and Nonclinical Summary 
Serlopitant is a small molecule, highly selective NK1-R antagonist that is administered orally 
and metabolized by cytochrome P-450 3A4 (CYP3A4), with a plasma half-life of 45-86 
hours. It binds with high affinity to the human NK1-R with a dissociation constant (Kd) of 46 
pM; displacing SP binding with a half-maximal inhibition concentration (IC50) of 61 pM. 
Serlopitant is a potent functional antagonist of SP-induced inositol phosphate generation. 
Serlopitant has been extensively studied in animal toxicology studies, including chronic 
toxicology and carcinogenicity studies. In non-clinical chronic toxicology studies in rats, 
mice and dogs, treatment related findings of potential clinical significance included increased 
salivation, decreased body weight gain and food consumption, slight changes in hematology 
and serum biochemistry parameters, mild increases in liver weight and mild 
histomorphologic changes. The histomorphologic changes were seen only in rats (not in dogs 
or mice) and included: very slight ovarian interstitial cell hypertrophy, mammary gland and 
uterine atrophy; decreased corpora lutea; increased histiocytes in lung and mesenteric lymph 
nodes; slight skeletal and cardiac muscle degeneration; slight increased hematopoiesis in 
bone marrow; and slight to moderate vacuolation in kidney tubules. These nonclinical 
findings occurred at systemic exposures exceeding those anticipated to provide efficacy of 
serlopitant for pruritus indications in humans (1 to 5 mg tablet daily). No cardiac lesions have 
been observed in dog toxicity studies up to 9 months in duration nor in a 3-month mouse 
range-finding study and 2-year mouse carcinogenicity study at exposure higher than the 
lowest level which caused cardiotoxicity in rats. The no observed adverse effect level 
(NOAEL) in rats for histomorphological changes in the reproductive tract, mammary gland 
and bone marrow provides a 2.5-fold margin for the maximum-targeted exposure (5 mg 
tablet daily). The rat NOAEL for histomorphological changes in muscle and kidney provides 
a 5-fold margin for the maximum-targeted exposure (5 mg tablet daily).  
In summary, the nonclinical toxicity noted with serlopitant provides no contraindications to 
the continuation of clinical trials via the oral route. Findings in the developmental toxicity 
studies support inclusion of women of childbearing potential in clinical trials in accordance 
with the study protocol and local regulatory guidances.  
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1.2.2 
Serlopitant Clinical Summary 
In humans, serlopitant has been administered to over 1000 individuals. Single doses up to 
400 mg have been well tolerated in young adult males and single doses up to 25 mg have 
been well tolerated in the elderly. Multiple doses of up to 50 mg a day for 4 weeks have been 
well tolerated in healthy young males, and a single (loading) dose of 15 mg followed by daily 
doses of 5 mg for 2 weeks have been well tolerated in elderly males and females. Forty-one 
(41) subjects received 4 mg liquid filled capsule (LFC) daily (bioequivalent to 5 mg tablets) 
for 1 year. Plasma concentrations of serlopitant appear to increase in a dose-proportional 
fashion in both young males and elderly subjects (males and females). Peak plasma 
concentrations after a single oral dose occurred at ~2 to 4 hours in both young and elderly 
subjects. A single loading dose of up to 15 mg followed by 6 to 8 weeks of up to 5 mg daily 
doses has been well tolerated in adults with chronic pruritus and prurigo nodularis (PN). 
Pharmacokinetic data demonstrate good plasma exposures with oral dosing, linear dose-
dependent increases in plasma concentration and systemic exposure, a plasma t1/2 
appropriate for once daily dosing, and mild effects of concomitant food ingestion. Central 
nervous system (CNS) positron emission tomography (PET) studies have demonstrated good 
CNS penetrance and > 90% NK1 receptor occupancy (RO) at plasma exposures anticipated 
to be safe and well tolerated. Three long-lived active hydroxylated metabolites are observed 
in humans: M1/M1a 
, M2/M2a 
, and M3 
. 
These metabolites were present at lower concentrations and were 2- to 9-fold less potent in 
vivo than the parent compound. The integrated pharmacokinetic/pharmacodynamic (PK/PD) 
analysis concluded that these metabolites are unlikely to contribute significantly to 
occupancy of the CNS NK1-R in humans. 
1.2.3 
Serlopitant in Pruritus-Related Studies 
Serlopitant has been evaluated in two completed Phase 2 studies of subjects with chronic 
pruritus (TCP-101 and TCP-102).  
TCP-101 
TCP-101 was a double-blind, placebo-controlled, multi-center study that compared 
serlopitant 0.25 mg, 1 mg, or 5 mg vs. placebo for the treatment of chronic pruritus. A total 
of 257 adult subjects 18-65 years of age with chronic pruritus were randomized to receive 
one of the four dose groups in a 1:1:1:1 randomization. Subjects received a loading dose of 
3 tablets on Day 1 and thereafter received 1 tablet per day for 6 weeks. The primary efficacy 
endpoint was itch severity as measured on a Visual Analog Scale (VAS), summarized as a 
percentage change from baseline. 
Mean percent decreases from Baseline in VAS score were larger in the active-treatment 
groups versus placebo at every scheduled post-baseline study visit. Overall, the results were 
the most profound for the serlopitant 1 mg and 5 mg groups. For the percent change from 
Baseline in VAS pruritus scores (the primary efficacy variable), the Week 6 pairwise least 
squares mean difference compared to placebo was 5.8 mm, 13.2 mm, and 14.2 mm for 
serlopitant 0.25 mg, 1 mg, and 5 mg, respectively.   
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The frequency of treatment-emergent adverse events (TEAEs) and study drug related adverse 
events (AEs) was higher in the serlopitant 1 mg and 5 mg groups compared to the serlopitant 
0.25 mg group, and the frequency in all three treatment groups were higher than in the 
placebo group. The frequency of AEs leading to study drug discontinuation was comparable 
in the serlopitant 5 mg and placebo group and higher than in the serlopitant 0.25 mg and 
1 mg groups. There was one serious adverse event (SAE) reported in the serlopitant 1 mg 
group (spontaneous abortion, considered not related). There were no deaths. The most 
common AEs in the serlopitant groups were diarrhea (6.2%, 1 mg group), upper respiratory 
tract infection (4.7%, 0.25 mg group), somnolence (4.7%, 5 mg group), nasopharyngitis 
(4.6%, 1 mg group), headache (4.7%, 5 mg group), urinary tract infection (3.1%, 5 mg 
group), dry mouth (3.1%, 1 mg group), nausea (3.1%, 1 mg group), arthralgia (3.1%, 0.25 
mg group), musculoskeletal pain (3.1%, 1 mg group) and pruritus (3.1%, 1 mg group). The 
most common AEs in the placebo group were headache (6.3%), nasopharyngitis (3.2%), 
upper respiratory tract infection (3.2%), urinary tract infection (3.2%) and asthma (3.2%).  
TCP-102 
TCP-102 was a randomized, double-blind, placebo-controlled multi-center study that 
evaluated serlopitant 5 mg vs. placebo for the treatment of PN A total of 128 adult subjects 
18-80 years of age with PN were randomized to receive serlopitant or placebo in a 1:1 
randomization. Subjects received a loading dose of 3 tablets on Day 1 followed by 1 tablet 
per day for 8 weeks. The primary efficacy endpoint was the average VAS score as recorded 
at the study visits. Results at Week 4 and Week 8 were the primary timepoints. 
Serlopitant 5 mg was superior to placebo for the reduction of pruritus as measured by change 
in average VAS from baseline. For the primary endpoint, change from baseline at Week 4 
and Week 8 by repeated measures analysis, the decrease from baseline was significantly 
greater in the serlopitant group than the placebo group, with a mean difference (serlopitant 
minus placebo) of -1.0 at Week 4 and -1.7 at Week 8. The mean difference at Week 2 was 
also significant, -0.9. In a post-hoc analysis of the percentage of subjects who were 4-point 
responders on average VAS at Week 8, 25.0% of placebo subjects and 54.4% of serlopitant 
subjects were 4-point responders. 
TEAEs were reported for 71.9% of serlopitant-treated subjects and 61.9% of placebo-treated 
subjects. The most frequently reported TEAEs in the serlopitant group were nasopharyngitis 
(17.2% serlopitant, 3.2% placebo), diarrhea (10.9% serlopitant, 4.8% placebo), and fatigue 
(9.4% serlopitant, 6.3% placebo). Treatment-related TEAEs were reported for 48.4% of 
serlopitant-treated subjects and 34.9% of placebo-treated subjects. The most frequently 
reported treatment-related TEAEs in the serlopitant group were fatigue (7.8%) and diarrhea, 
peripheral edema, dizziness, and headache (each 6.3%). Most TEAEs were mild or moderate; 
severe TEAEs were reported for 9.4% of serlopitant-treated subjects and 4.8% of placebo-
treated subjects. There were no deaths during the study. Five subjects (3 serlopitant, 
2 placebo) had SAEs. The SAEs were actinic elastosis, depression, dizziness, and vertigo in 
the serlopitant group; and bradycardia, syncope, respiratory failure, and neurodermatitis in 
the placebo group. Nine subjects (3 serlopitant, 6 placebo) discontinued due to TEAEs. 
No clinically relevant changes were observed in chemistry, hematology, vital signs, or 
electrocardiogram (ECG) results. 
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The results of the Phase 2 studies in PN and chronic pruritus, together with the extensive 
nonclinical and clinical safety data and experience with serlopitant to date and the scientific 
rationale for NK1-R inhibition in the treatment of pruritus, serve to support further evaluation 
of serlopitant for the long-term treatment of pruritus in patients with PN, AD, or psoriasis. 
The potential benefits of continued clinical study outweigh the potential risks. The data 
obtained from this long-term study will inform the risks and benefits of long-term exposure 
(chronic or repeated intermittent use for longer than 6 months). The risk to subjects in this study 
will be minimized by medical and safety monitoring (see Section 3.4.1). 
Please refer to the Investigator’s Brochure for further information regarding serlopitant. 
2 
STUDY OBJECTIVES  
The primary objective of this study is to assess the long-term safety of serlopitant in adults 
with pruritus associated with PN, AD, or psoriasis. 
The secondary objectives of this study are to assess the change in severity of pruritus in 
subjects with PN, AD, or psoriasis using the worst-itch numeric rating scale (WI-NRS); to 
assess the change in severity and extent of PN using the Investigator’s Global Assessment of 
PN Stage (IGA PN-S), for those subjects with PN; and to assess whether serlopitant produces 
physical dependence. 
3 
STUDY DESIGN 
3.1 
Overall Study Design 
This is a multicenter, open-label study to assess the long-term safety of serlopitant in adults 
with pruritus associated with PN, AD, or psoriasis. Eligible subjects who have completed 
selected studies of serlopitant may be given the opportunity, at the investigator’s discretion, 
to consent to and participate in this open-label study, regardless of their treatment allocation 
in prior studies. If deemed necessary by Menlo Therapeutics to meet enrollment objectives, 
eligible subjects who have not participated in a prior serlopitant study may also be enrolled in 
study MTI-107. Approximately 120 study sites may enroll subjects in this long-term safety 
study. 
This study will consist of two periods, for a total study period of approximately 57 weeks: 
• Treatment period: 52 weeks 
• Post-drug observation period: 5 weeks 
 
During the treatment period, subjects will take one serlopitant 5 mg tablet once daily orally 
(Section 5.3).  
Standard therapy for the concurrent skin lesions and pruritus may be employed during this 
study (Section 5.7.1).  
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The WI-NRS during a 24-hour recall period will be assessed by the subject at each study 
visit. 
For those subjects with PN, the severity and extent of PN will be assessed at selected visits, 
using the IGA-PN-S, and photographs of representative areas with PN will be taken at 
selected visits at a subset of sites. 
The Dermatology Life Quality Index (DLQI) will be administered at selected visits. 
After completion of the 52-week treatment period, all subjects will enter a 5-week post-drug 
observation period. Subjects who discontinue treatment early will have a post-drug 
observation visit through 5 weeks after their last dose of serlopitant. During this monitored 
discontinuation period, solicited safety evaluations will assess the potential for serlopitant to 
produce physical dependence. 
3.2 
Rationale for Study Design and Dose Selection 
The current MTI-107 study is designed to confirm the long-term safety of serlopitant for the 
treatment of pruritus in patients with PN, AD, and psoriasis. The 5 mg dose of serlopitant 
was selected for this study based on the favorable efficacy, safety, and tolerability profile of 
serlopitant at this dose level in completed studies.  
3.3 
Study Endpoints 
3.3.1 
Safety Endpoints 
The safety endpoints are as follows: 
• Incidence of TEAEs and SAEs 
• Change from baseline in clinical laboratory parameters   
• Change from baseline in vital sign and ECG parameters 
• Change from baseline in the Hospital Anxiety and Depression Scale (HADS)  
• Change from baseline in the Epworth Sleepiness Scale (ESS)   
• Assessment of physical dependence following chronic study drug exposure, in the 
5-week post-drug discontinuation period.  
 
3.3.2 
Efficacy Endpoints 
The efficacy endpoints are as follows: 
• Change from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52  
• Change from baseline in DLQI (symptoms and feelings, daily activities, leisure, work or 
school performance, personal relationships, and treatment) to Weeks 20, 36 and 52 
• Change from baseline in IGA PN-S to Weeks 4, 8, 20, 28, 36, 44, and 52 
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3.4 
Safety Review 
3.4.1 
Safety Monitoring Team 
An internal safety monitoring team consisting of representatives from Menlo Therapeutics 
Inc. and its designees will monitor safety data on a regular basis throughout the study. 
4 
SELECTION OF STUDY POPULATION 
4.1 
Study Population 
Up to 700 adult subjects with pruritus associated with PN, AD, or psoriasis will be enrolled 
in this study. 
4.2 
Inclusion Criteria 
Subjects must meet the following criteria to be enrolled into the study: 
1. Male or female, age 18 years or older at consent. 
2. Subject reports pruritus in the 24-hour period prior to enrollment and: 
a. Has completed a prior applicable clinical study of serlopitant without an SAE 
that was assessed as likely related to the study drug (For participants from 
study TCP-102, the WI-NRS score must be ≥ 7 in the 24-hour period prior to 
the Baseline visit.) 
OR  
b. Has not participated in a prior clinical study of serlopitant and has a clinical 
diagnosis of PN, AD, or psoriasis, and has a WI-NRS score ≥ 7 in the 24-hour 
period prior to the Baseline visit, and Sponsor has approved enrollment. 
3. All female subjects who are of childbearing potential must be willing to practice highly 
effective contraception (i.e., pregnancy prevention method with a failure rate of <1% per 
year, refer to Section 7.1.5 for acceptable methods of contraception) from the time of the 
Baseline visit until 5 weeks after last dose of study drug. 
4. Willing and able (has adequate cognitive ability, in the investigator’s opinion) to comply 
with study visits and study related requirements including providing written informed 
consent. 
 
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4.3 
Exclusion Criteria 
Subjects who meet any of the following criteria are not eligible for participation in the study: 
1. Presence of malignancy within 5 years prior to enrollment (exception for non-melanoma 
cutaneous malignancies). 
2. Any known major psychiatric diagnosis, such as major depressive disorder, bipolar 
disorder, schizophrenia, psychotic disorder, intellectual disability, severe alcohol use 
disorder, which may confound the assessment of serlopitant safety or efficacy, or 
interfere with the subject’s ability to comply with protocol-mandated activities, within 3 
years prior to enrollment.   
3. Untreated or inadequately treated thyroid, adrenal, or pituitary nodules or disease, or 
history of thyroid malignancy; or the presence of any medical condition or disability, 
that, in the investigator’s opinion, could interfere with the assessment of safety in this 
study or compromise the safety of the subject.  
4. Treatment with any investigational therapy within 4 weeks or 5-half-lives prior to 
enrollment (whichever is longer) or expected participation in another clinical study 
involving an investigational product or device during the subject’s participation in MTI-
107. 
5. Treatment with other neurokinin-1 receptor (NK1-R) antagonists (e.g., aprepitant, 
fosaprepitant, rolapitant) within 4 weeks prior to enrollment. 
6. Treatment with strong cytochrome P450 3A4 inhibitors within 4 weeks prior to 
enrollment (Appendix B). 
7. Currently pregnant or breastfeeding or planning to become pregnant during the study. 
 
5 
STUDY DRUG 
5.1 
Study Drug Supply, Route of Administration, and Storage 
The study drug in this study is serlopitant 5 mg in a film-coated tablet formulation for oral 
administration. The serlopitant tablets contain microcrystalline cellulose, mannitol, 
croscarmellose sodium, silicon dioxide, sodium lauryl sulfate, and magnesium stearate, and 
are film coated with Opadry® Brown.  
The study drug will be provided in bottles that can be stored at room temperature (59-86°F, 
15-30°C). 
Each bottle will each contain 18 serlopitant tablets.  
Additional details regarding study drug supplies can be found in the Pharmacy Manual. 
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5.2 
Labeling and Study Drug Accountability 
The study drug will be appropriately packaged and labeled in bottles with 18 tablets per 
bottle. The study drug supplied for this study is not to be used for any purpose other than this 
study, and study drug accountability must be maintained for all bottles distributed to the 
investigative site. 
Additional details regarding study drug labeling and accountability can be found in the 
Pharmacy Manual. 
5.3 
Dosing Regimen 
During the treatment period, subjects will take one serlopitant 5 mg tablet once daily orally.  
Subjects will be instructed to take all doses from Baseline Visit (Study Day 1) until the Week 
52 Visit, once a day. Study drug may be taken with or without food. 
Should the study drug be withheld (without intent to discontinue study drug, Section 5.6), the 
drug may be resumed at the discretion of the investigator, at the same dosing regimen.  
5.4 
Dose Modification 
No dose modification of study drug will be allowed during this study.  
5.5 
Missed or Delayed Doses 
Each dose of study drug after the first dose must be administered once daily. If a dose is 
missed, that dose will be considered and documented as a missed dose.  Dosing should 
resume as directed the next day. 
5.6 
Study Drug Discontinuation 
Subjects should be discontinued from study drug in the following situations: 
• Any medical condition that may jeopardize the subject’s safety if study drug is continued, 
in the investigator’s and/or Sponsor’s opinion; this may include the development of 
persistently (2 successive occasions) abnormal thyroid function tests (TSH >10, or 
TSH > 6 with low free T4; TSH <0.1, or TSH < 0.35 with high free T4); abnormal 
morning prolactin, cortisol, or corticotropin levels; or signs and symptoms of adrenal 
insufficiency 
• Baseline serum creatinine, total bilirubin, alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) > 2.5 times the upper limit of normal (ULN) (exception may be 
made for retesting within 28 days of enrollment as approved by the Medical Monitor) 
• A female subject desires to become pregnant at the current time, stops contraception or 
expels her intrauterine device/implant, or becomes pregnant 
• A female subject has new breast findings (e.g. a palpable mass or abnormal 
mammography, discharge), or has abnormal vaginal discharge or bleeding 
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• The subject decides to discontinue study drug, or withdraws consent from the study 
• The subject reports use of a strong CYP3A4 inhibitor (as listed in Appendix B) within 4 
weeks of the study visit at which it was reported, initiates any investigational medication, 
or other NK1-R antagonist (exception may be made for use of approved NK1-R 
antagonist for less than 5 continuous days) 
• Discontinuation is deemed to be in the best interest of the subject, in the investigator’s 
and/or Sponsor’s opinion, including evidence that the subject does not meet 
inclusion/exclusion criteria intended primarily for safety reasons, or a persistent lack of 
adherence to study procedures 
 
The Sponsor or designee should be contacted within 24 hours of investigator’s awareness of 
any study drug discontinuation due to an AE or pregnancy. Investigators should make every 
effort to contact the Sponsor or designee before discontinuing study drug, if possible. 
Subjects who discontinue study drug prior to completing the treatment period will enter a 
5-week follow-up period following the last dose of study drug (Section 6.4.10). Every effort 
should be made for subjects to complete this follow-up visit after a subject has discontinued 
from study drug.  
5.7 
Concomitant and Excluded Therapies 
Concomitant therapies include any therapies (including over-the-counter medications) used 
by a subject from initiation of study drug through the follow-up period. A record of all 
medications used will be maintained for each subject throughout the study. Reported 
information will include a description of the type of drug, treatment period, dosing regimen, 
the route of administration, and drug indication. The use of any concomitant medication must 
relate to the subject’s medical history or to an AE, except for vitamins/nutritional 
supplements and routine preventative immunizations.  
5.7.1 
Excluded Therapies 
The following therapies and activities are excluded from the Baseline visit through the 
follow-up period: 
• NK1-R antagonists (other than study drug, exception may be made for use of approved 
NK1-R antagonist for less than 5 continuous days) 
• Strong CYP3A4 inhibitors (See Appendix B; exceptions may be made for use within 4 
weeks of the study visit at which it was reported) 
• Any investigational drug therapy other than serlopitant 
 
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Use of any excluded therapies should be reported as soon as possible, and will be recorded as 
protocol deviations for subjects who receive them. Subjects may be discontinued from the 
study drug (Section 5.6). 
5.8 
Assignment to Treatment  
Eligible subjects will receive serlopitant 5 mg tablets. 
5.9 
Treatment Compliance 
Records of study drug used, dosages administered, and intervals between visits will be kept 
during the study. Subjects will be asked to return all partially used and empty bottles to the 
study site at each visit. The site staff will count and record the number of remaining tablets in 
each returned bottle. Missed doses will be recorded as reported by the subject. A subject who 
has deviated significantly from the once-daily dosing regimen will be counseled. 
6 
STUDY SCHEDULE AND ASSESSMENTS  
6.1 
Efficacy Parameters 
6.1.1 
Itch Numeric Rating Scale 
The Itch NRS is a validated, self-reported instrument for measurement of itch intensity. WI-
NRS scores will be captured as per Appendix A. Subjects are asked to rate the intensity of 
their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher 
scores indicate greater itch intensity. In this study, the subject is asked to rate the intensity of 
their worst itch (WI-NRS) during a 24-hour recall period prior to the specified visit; the 
questionnaire is provided in Appendix C.   
6.1.2 
Investigator’s Global Assessment of PN Stage 
The IGA PN-S is an instrument used to assess the overall number and thickness of PN 
lesions at a given time point, as determined by the investigator. It consists of a 5-point scale 
ranging from 0 (clear) to 4 (severe), as provided in Appendix D. The IGA PN-S uses clinical 
characteristics including the number of nodules and their thickness, as guidelines for the 
overall severity assessment. IGA PN-S scores will be captured as per Appendix A. Each 
assessment during the study must be done by the principal investigator (PI) or designee. 
Every effort should be made to ensure that all assessments for a given subject are done by the 
same individual throughout the study. However, a change in assessor for a given subject, 
though not ideal, will not be considered a protocol deviation. 
6.1.3 
Dermatology Life Quality Index  
DLQI is a dermatology specific quality of life instrument designed to assess the impact of the 
skin disease on a subject’s quality of life over the prior week. It is a ten-item questionnaire 
that assesses overall quality of life (QOL) and six aspects that may affect QOL (symptoms 
and feelings, daily activities, leisure, work or school performance, personal relationships, and 
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treatment), and is provided in Appendix E. The DLQI questionnaire will be collected as per 
Appendix A. 
6.1.4 
Photographs 
At selected investigative sites, optional photographs of representative areas with PN 
involvement will be taken at multiple time points, as per Appendix A. These areas may 
include the extensor surfaces of both arms and both legs (overview of both legs, detail of 
lower legs), and the abdomen and back. The central photography vendor will provide 
photographic equipment to the sites for use during the study. Detailed instructions will be 
provided in a Photography Manual. 
6.2 
Safety Parameters 
Safety assessments will consist of monitoring and recording protocol-defined AEs and SAEs; 
vital signs; physical examinations; clinical laboratory assessments; ECGs; and other 
protocol-specified tests that are deemed critical to the safety evaluation of the study drug. 
6.2.1 
Vital Signs 
Vital signs will include measurements of heart rate, blood pressure, respiration rate, and 
temperature after the subject has been calmly resting (seated or supine) for a minimum of 
5 minutes. Vital signs will be assessed as per Appendix A and at unscheduled study visits 
when clinically indicated. When possible, assessment of vital signs should precede blood 
draw.  
6.2.2 
Physical Examination 
Physical examinations will be performed as per Appendix A and at unscheduled study visits 
when clinically indicated. A complete physical examination will be performed at the 
Baseline visit, while subsequent examinations will be abbreviated and targeted to changes in 
disease activity and/or subjects’ symptoms. The subjects’ height and weight will be measured 
as per Appendix A. For female subjects with targeted breast examinations, please perform 
breast examination after blood draw for clinical laboratory tests.   
6.2.3 
Clinical Laboratory Assessments 
Samples for clinical laboratory assessments will be collected as per Appendix A and at 
unscheduled study visits when clinically indicated, and analyzed at a central laboratory 
unless otherwise specified. When possible, blood draws should follow ECGs and vital sign 
measurements if they occur on the same visit.  
Detailed instructions regarding sample collection, preparation, and shipment can be found in 
the laboratory manual. Laboratory assessments will include the following, and are ideally 
performed in the morning, particularly at visits with endocrine assessments (Baseline, Weeks 
12, 28, and 52): 
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• Hematology: hematocrit, hemoglobin, red blood cell count, red blood cell indices, 
platelets, white blood cell count, white blood cell differential (neutrophils, lymphocytes, 
monocytes, basophils, eosinophils) 
• Chemistry: sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, 
creatinine, calcium, phosphorus, magnesium, albumin, uric acid, total protein, alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total 
bilirubin, lactate dehydrogenase (LDH), lipid panel 
• Endocrine: TSH, free T4, cortisol, corticotropin (adrenocorticotropic hormone, ACTH), 
prolactin  
- 
Standard cosyntropin stimulation testing should be performed on subjects with low 
cortisol level (i.e. < 3.0 mcg/dL); the investigator should discuss low cortisol (and 
relevant low corticotropin) results with the medical monitor. 
• Pregnancy testing: all females of childbearing potential will have a local urine pregnancy 
test performed. Monthly pregnancy testing can be performed in between visits (and 
recorded as an Unscheduled visit), and at any time per the investigator’s discretion, and  
as required by local authorities (e.g. in Austria). Positive or equivocal urine pregnancy 
test results will be confirmed by a serum pregnancy test analyzed at a central laboratory 
• Reproductive endocrinology (for all female subjects under 55 years of age at consent): 
serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, 
progesterone, anti-Mullerian hormone (AMH)  
• For participants from study TCP-102 or those who had not participated in a prior clinical 
study of serlopitant, additional optional studies for the etiology of PN (if applicable) will 
be supported through local procedural and/or laboratory assessments (test kits not 
supplied by Sponsor). Studies may include, but are not limited to, iron studies (ferritin, 
serum iron), serum IgE, hepatitis B and C serology, HIV testing, skin biopsy and 
pathology interpretation, urea breath test for Helicobacter pylori, and allergy testing 
(patch, prick, or blood testing); the investigator should discuss the need for such studies 
with the medical monitor during the Screening period 
 
6.2.4 
Electrocardiogram  
A standard 12-lead ECG will be performed after the subject has been calmly resting in a 
supine position for a minimum of 5 minutes before obtaining the ECG. When possible, ECGs 
should precede measurement of vital signs and blood draw for clinical laboratory tests. ECGs 
will be performed as per Appendix A and at unscheduled study visits when clinically 
indicated. ECGs will be reviewed and reported by a central ECG vendor. The ECG machine 
and detailed instructions will be provided by the ECG vendor. 
6.2.5 
Hospital Anxiety and Depression Scale 
The HADS is a QOL instrument designed to assess the severity of anxiety and depression 
over the prior week, developed in a hospital outpatient clinic, but also valid in community 
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settings and primary care medical practice.  The questionnaire takes approximately 2 to 5 
minutes to complete, and is provided in Appendix F. The HADS questionnaire will be 
collected as outlined in Appendix A. 
6.2.6 
Epworth Sleepiness Scale 
The ESS is a QOL instrument intended to measure daytime sleepiness by use of a very short 
questionnaire. The questionnaire takes approximately 2 to 3 minutes to complete, and is 
provided in Appendix G. The ESS questionnaire will be collected as outlined in Appendix A. 
6.2.7 
Assessment of Potential for Physical Dependence 
NK1-R antagonist dependence has not previously been described and therefore a drug class-
specific, reliable and sensitive instrument for the assessment of withdrawal symptoms has not 
been developed. A surrogate assessment tool, such as those developed for opioid or 
benzodiazepine dependence, is not available.  
In order to provide a comprehensive set of assessments for physical dependence and 
withdrawal symptoms following chronic exposure to the study drug, the HADS and ESS 
instruments will be administered at baseline and throughout the study period, as well as 3-
days and 7-days following the last dose of study drug, and then weekly throughout the 5-
week post-study drug observation period. In addition, vital signs will be assessed at each 
post-study drug observation visit, and an ECG and laboratory analyses will be assessed at the 
5-week post-study drug visit. All TEAEs reported during this period will be medically 
reviewed to assess for possible physical dependence or withdrawal signs or symptoms. 
6.3 
Subject Flow Diagram 
The visit schedule and assessments are summarized in Appendix A.  
6.4 
Study Visits 
The following sections describe the procedures and assessments to be performed at each 
study visit. Details of each procedure and assessment can be found in Sections 6.1 and 6.2. 
The timing of each study visit is relative to the day of enrollment (Baseline Visit). 
Unscheduled visits may be performed as necessary, and may include procedures or 
assessments deemed necessary by the investigator and to conduct monthly urine pregnancy 
testing on females of childbearing potential in between regularly scheduled visits. 
Female subjects who report periodic menstruation will be asked to complete a menstrual 
diary (paper form) throughout the study. 
6.4.1 
Baseline Visit 
The Baseline Visit may coincide with the final visit of the MTI-103, MTI-105, MTI-106, or 
MTI-109 studies. 
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The following procedures are to be performed at the Baseline Visit (Day 1): 
• Obtain written informed consent prior to any protocol-mandated procedures (must be 
obtained prior to any other assessments) 
• Confirm subject’s eligibility based on the inclusion/exclusion   
• Collect demographic information (when permitted by regional laws or guidelines: sex, 
date of birth, race/ethnicity)  
• Collect any concomitant medications 
• Review and record subject’s medical history, including ongoing TEAEs from prior study 
(if applicable) 
- 
Female subjects should be queried regarding history of, or current, breast masses or 
abnormal discharge, and history of mammography (if applicable), and history of 
abnormal vaginal bleeding or discharge 
• Perform complete physical examination (including height and weight)  
• Obtain ECG  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Draw blood for clinical laboratory tests (exception: participants in MTI-103, MTI-105, 
MTI-106, and MTI-109 who have had these labs in prior 14 days, in the context of that 
study) 
- 
Hematology 
- 
Chemistry 
- 
Endocrine  
- 
Reproductive endocrine labs for females under 55 years of age at consent  
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
DLQI 
- 
HADS 
- 
ESS 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Register Baseline Visit into the Interactive Web Response System (IWRS)  
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• Dispense study drug 
• Provide a menstrual diary to female subjects who report periodic menstruation   
• Confirm next scheduled visit date 
6.4.2 
Week 4 Visit 
The Week 4 Visit occurs 28 days (±7 days) after the Baseline Visit. At the Week 4 Visit, the 
following procedures and assessments are to be performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.3 
Week 8 Visit 
The Week 8 Visit occurs 56 days (±7 days) after the Baseline Visit. At the Week 8 Visit, the 
following procedures and assessments are to be performed:  
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• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.4 
Week 12 Visit 
The Week 12 Visit occurs 84 days (±7 days) after the Baseline Visit. At the Week 12 Visit, 
the following procedures and assessments are to be performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination, including weight  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
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- 
Endocrine  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.5 
Week 20 Visit 
The Week 20 Visit occurs 140 days (±7 days) after the Baseline Visit. At the Week 20 Visit, 
the following procedures and assessments are to be performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
DLQI 
- 
HADS 
- 
ESS 
• Perform IGA PN-S (for subjects with PN only) 
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• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.6 
Week 28 Visit 
The Week 28 Visit occurs 196 days (±7 days) after the Baseline Visit. At the Week 28 Visit, 
the following procedures and assessments are to be performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination, including weight  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
- 
Endocrine 
- 
Reproductive endocrine labs for females under 55 years of age at consent   
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
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6.4.7 
Week 36 Visit 
The Week 36 Visit occurs 252 days (±7 days) after the Baseline Visit. At the Week 36 Visit, 
the following procedures and assessments are to be performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination  
• Obtain ECG  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
DLQI 
- 
HADS 
- 
ESS 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.8 
Week 44 Visit 
The Week 44 Visit occurs 308 days (±7 days) after the Baseline Visit. At the Week 44 Visit, 
the following procedures and assessments are to be performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
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• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination  
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Perform IGA PN-S (for subjects with PN only) 
• Collect returned study drug 
• Review study drug compliance with re-training as required 
• Register visit into the IWRS and utilize IWRS to assign new bottles of study drug 
• Confirm next scheduled visit date 
 
6.4.9 
Week 52 Visit 
The Week 52 Visit occurs 364 days (±7 days) after the Baseline Visit. At the Week 52 Visit, 
the following procedures and assessments are to be performed:  
• Register visit into the IWRS 
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination, including weight 
• Obtain ECG  
• Obtain vital signs  
• Draw blood for clinical laboratory tests 
- 
Hematology 
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- 
Chemistry 
- 
Endocrine 
- 
Reproductive endocrine labs for females under 55 years of age at consent  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
DLQI 
- 
HADS 
- 
ESS 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug 
• Confirm next scheduled visit date 
 
6.4.10 
Early Treatment Discontinuation Visit 
The Early Treatment Discontinuation (ETD) Visit occurs within 35 days of last dose for 
subjects who discontinue serlopitant treatment prior to Week 52.  
At the ETD Visit, the following procedures and assessments are to be performed:  
• Register visit into the IWRS 
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination, including weight 
• Obtain ECG   
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) 
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• Draw blood for clinical laboratory tests 
- 
Hematology 
- 
Chemistry 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
DLQI 
- 
HADS 
- 
ESS 
• Perform IGA PN-S (for subjects with PN only) 
• Obtain photos (only PN subjects that signed photography consent, only at sites selected 
for photography) 
• Collect returned study drug   
 
6.4.11 
Post-Drug Observation Visits 
There are six (6) post-drug observation visits. 
The Post-Drug Observation Visits occur 3 days (±1 days), 7 days (±3 days), 14 days (±3 
days), 21 days (±3 days), 28 days (±3 days), and 35 days (±3 days) after the Week 52 Visit.  
At the Post-Drug Observation Visits, the following procedures and assessments are to be 
performed:  
• Review menstrual diary and record dates of menstrual flow (if applicable) 
• Assess and record any AEs and/or SAEs 
• Assess and record any changes in the subject’s concomitant medications 
• Female subjects should be queried for presence of new breast masses or abnormal 
discharge, and abnormal vaginal bleeding or discharge 
• Perform targeted physical examination, including weight (Only required at post-drug 
observation visit 35 days after Week 52 visit) 
• Obtain ECG (Only required at post-drug observation visit 35 days after Week 52 visit) 
• Obtain vital signs  
• Perform a urine pregnancy test for females of childbearing potential (with positive or 
equivocal results to be confirmed by a serum pregnancy test) (Only required at post-drug 
observation visit 35 days after Week 52 visit) 
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• Draw blood for clinical laboratory tests (Only required at post-drug observation visit 35 
days after Week 52 visit) 
- 
Hematology 
- 
Chemistry 
• Ask subject to complete WI-NRS 
• Ask the subject to complete the following questionnaires: 
- 
HADS 
- 
ESS 
• Register visit into the IWRS (Only at post-drug observation visit 35 days after Week 52 
visit) 
 
6.4.12 
Early Termination 
Early termination of a subject from the study may occur due to loss to follow-up or 
withdrawal of consent by the subject. In accordance with legal requirements and 
International Conference on Harmonization (ICH) – Good Clinical Practice (GCP) 
guidelines, every subject or his/her legal representative has the right to withdraw from the 
study at any time and without providing reasons. If provided, the reason (adverse event, 
study burden, lack of efficacy, other) a subject withdrew consent will be recorded in the 
electronic Case Report Form (eCRF). Attempts to contact subjects who are suspected of 
being lost to follow-up must be documented in the subject’s source documents. 
7 
ASSESSMENT OF SAFETY 
7.1 
Definitions 
7.1.1 
Adverse Event 
An AE is any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. An AE can be any unfavorable and unintended sign 
(e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a drug, without any judgment about causality. 
AEs include treatment emergent exacerbations of pre-existing illnesses and AEs that occur as 
a result of protocol-mandated interventions. 
7.1.2 
Serious Adverse Event  
An AE is considered “serious” if it results in any of the following outcomes: 
• Death 
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• Life-threatening AE (i.e. the subject was at immediate risk of death from the event as it 
occurred. An event that might have led to death if it had occurred with greater severity is 
not “life-threatening”) 
• Inpatient hospitalization or prolongation of existing hospitalization  
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• Congenital anomaly/ birth defect 
• Important medical event (i.e. an event that may not result in death, be life-threatening, or 
require hospitalization, but which may be considered serious by the investigator or 
Sponsor, as it may jeopardize the subject and may require medical/surgical intervention 
to prevent one of the outcomes listed above). Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, 
blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse. 
 
The following are not considered SAEs: a visit to the emergency room or other hospital 
department < 24 hours that does not result in admission (unless considered an important 
medical or life-threatening event), an elective surgery planned prior to signing consent, 
admission as per protocol for planned medical/surgical procedure, and/or routine health 
assessments requiring admission for baseline/trending of health status (e.g. routine 
colonoscopy). 
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an 
AE (e.g. mild, moderate, or severe pain); the event itself may be of minor medical 
significance (e.g. severe back pain). “Serious” is a regulatory definition, as defined above. 
Seriousness (not severity) serves as the basis for defining regulatory reporting obligations.  
Severity and seriousness should be independently assessed when recording AEs and SAEs on 
the eCRF. 
7.1.3 
Abnormal Physical Exam, Laboratory, Vital Sign, and Electrocardiogram 
Findings  
Abnormal physical exam findings that are clinically significant and are identified prior to the 
first dose of study drug should be recorded as medical history. New or worsening clinically 
significant abnormal physical exam findings identified after the first dose of study drug 
should be recorded as AEs.   
Only abnormal laboratory, vital sign, and ECG findings that are considered clinically 
significant by the investigator (e.g. require active management or are associated with 
accompanying symptoms/signs) will be recorded as medical history or AEs on the eCRF. 
Abnormal laboratory, vital sign, and ECG findings that occur prior to the first dose of study 
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drug should be recorded as medical history, and abnormal findings that occur after the first 
dose of study drug should be recorded as AEs. 
If the clinically significant laboratory, vital sign, or ECG abnormality is a sign associated 
with a confirmed disease or condition (e.g. elevated creatinine in a subject diagnosed with 
chronic kidney disease), only the diagnosis (chronic kidney disease) needs to be recorded on 
the AE eCRF (rather than listing individual test findings as AEs).  
Separate instances of the same clinically significant laboratory, vital sign, or ECG 
abnormality across visits should not be recorded as separate AEs or SAEs. 
7.1.4 
Deaths  
Any deaths that occur from the time of informed consent to the follow-up visit, regardless of 
attribution, must be reported within 24 hours of investigator’s awareness of the death. See 
Safety Form Completion Instructions for complete instructions. 
The Sponsor should be provided a copy of any post-mortem findings and/or relevant medical 
reports, including histopathology. 
7.1.5 
Pregnancies and Contraception Requirements for Females 
For the purposes of this study, a female of childbearing potential is defined as any female 
who has experienced menarche and is pre-menopausal, unless permanently surgically sterile 
(e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy). A postmenopausal 
state is defined as no menses for 12 months without an alternative medical cause in a 
previously menstruating female.  
For the purposes of this study, acceptable contraception is defined below based on 
Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals: ICH M3(R2) dated January 2010, and other available 
guidelines (“U.S. Medical Eligibility Criteria for Contraceptive Use” 2010; 
“Recommendations related to contraception and pregnancy testing in clinical trials” 2014; 
“M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals” 2010):  
All female subjects of childbearing potential must use highly effective contraception, which 
includes the use of one or more of the following acceptable methods:  
1. Surgical sterilization (e.g., bilateral tubal occlusion or ligation, hysterectomy, bilateral 
salpingectomy, bilateral oophorectomy) 
2. Total (as opposed to periodic or cyclic) abstinence from heterosexual intercourse, 
only if planned for the entire duration of the study period and consistent with the 
preferred and usual lifestyle for the subject 
3. Hormonal contraception associated with consistent inhibition of ovulation; these may 
include (but are not necessarily limited to) oral, intravaginal, implantable, injectable, 
or transdermal delivery methods  
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4. Intrauterine device/system  
5. Exclusive (sole) monogamous intercourse with a sterilized (i.e., vasectomized) or 
otherwise non-fertile (e.g., castrated) male partner; the male partner must have 
received medical assessment of the surgical success 
Progesterone-only oral contraceptives are excluded as a highly effective method of 
contraception, as they do not consistently inhibit ovulation. Male or female condoms with or 
without spermicide, and female caps, diaphragms, and sponges with spermicide, or 
combinations (double barrier) are also excluded as highly effective contraceptive methods. 
Any pregnancy occurring in a female subject or the female partner of a male subject, from 
the first study drug administration through the required follow-up visit must be reported 
within 24 hours of the investigator’s awareness of the pregnancy. See Safety Form 
Completion Instructions for complete instructions.  
The investigator will follow the pregnancy to delivery or other pregnancy outcome.  
Pregnancy in a female clinical trial subject or female partner of a male clinical trial subject is 
not an SAE per se. Complications of such pregnancies (for example, spontaneous abortion) 
may qualify as SAEs and should be reported as such even if they occur after the follow-up 
visit. Any congenital anomalies/birth defects must be recorded and reported as SAEs. See 
Safety Form Completion Instructions for complete instructions.  
7.1.6 
Worsening of Pruritus or Underlying Pruritic Skin Disease 
Pruritus or the underlying pruritic skin disease (PN, AD, or psoriasis) should be recorded as 
an AE or SAE only if considered by the investigator to have worsened in severity beyond the 
subject’s typical fluctuations. It is important to include a description of the nature of the 
unexpected worsening when recording the AE or SAE (e.g. new PN lesions in previously 
uninvolved skin). 
7.2 
Methods and Timing for Recording and Reporting Adverse Events 
7.2.1 
Adverse Event Reporting Period 
Any AE occurrence during the study must be recorded on source documentation and eCRF at 
the site, in accordance with protocol instructions.  
AEs and SAEs will be recorded from the first study drug administration through the follow-
up visit. After the 5-week follow-up visit, only SAEs that are believed to be drug-related 
should be reported. 
After informed consent, but prior to initiation of study drug, only SAEs considered by the 
investigator to be caused by a protocol-mandated intervention will be collected (e.g. SAEs 
related to invasive procedures such as blood collection). These procedure-related SAEs 
should only be reported on the source documents and SAE form, not on the AE eCRF. 
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Subjects who undergo Baseline visit procedures but are not enrolled into the study will not 
have SAEs recorded in the clinical database. 
7.2.2 
Eliciting Adverse Events 
Investigators will seek information on AEs and SAEs at each subject contact through the 
follow-up visit. All AEs and SAEs, whether reported by the subject or noted by authorized 
study personnel, will be recorded in the subject’s medical record and on the AE eCRF page, 
and, if serious, on the SAE form. For each AE and SAE recorded, the investigator will make 
an assessment of seriousness, severity, and causality. 
7.2.3 
Assessment of Severity 
All AEs entered into the eCRF will be graded for severity using the National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 (“Common 
Terminology Criteria for Adverse Events (CTCAE)” 2010) to describe the maximum 
intensity of the adverse event.   
If the AE cannot be found in the event-specific NCI CTCAE grading criteria, the investigator 
should use the definitions for Grade 1, 2, 3, and 4 in Table 1. 
 Table 1 
Adverse Event Grading 
Grade 
Severity 
Alternate Descriptiona 
1 
Mild (apply event-specific NCI 
CTCAE grading criteria) 
Asymptomatic or mild symptoms; clinical or 
diagnostic observations only; intervention not 
indicated. 
2 
Moderate (apply event-specific NCI 
CTCAE grading criteria) 
Minimal, local or noninvasive intervention 
indicated; limiting age-appropriate 
instrumental activities of daily living (ADLb) 
3 
Severe (apply event-specific NCI 
CTCAE grading criteria) 
Severe or medically significant but not 
immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; 
disabling; limiting self care ADLc 
4 
Very severe, life threatening, or 
disabling (apply event-specific NCI 
CTCAE grading criteria) 
Life-threatening consequences; urgent 
intervention indicated. 
5 
Death related to AE 
 
a 
Use these alternative definitions for Grade 1, 2, 3, and 4 events when the observed or reported AE is not in 
the NCI CTCAE listing. A semi-colon indicates ‘or’ within the alternate description of the grade. 
b 
Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
c 
Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden. 
Source: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 
 
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Note that severity, a measure of intensity, is not equivalent to seriousness, a regulatory 
definition of outcome. Regardless of severity, some AEs may meet the criteria for 
seriousness. See Section 7.1.2 for the definition of an SAE. 
If an adverse event changes in severity during the same study period (e.g., treatment period), 
only the highest severity grade will be recorded on the eCRF.  
7.2.4 
Assessment of Causality 
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious). An investigator’s causality assessment is the determination of whether there exists a 
reasonable possibility that the investigational product caused or contributed to an AE. 
Causality of an AE will be assessed by the investigator using the following terms: 
• Likely Related: A reaction that follows a reasonable temporal sequence from 
administration of the study drug; that follows a known or expected response pattern to the 
suspected study drug; and for which other potential etiologies are considered less likely 
factors than the study drug. 
• Likely Unrelated: A reaction that, considering all potential etiologies, is most likely due 
to factors other than the study drug. 
 
7.3 
Follow-up of Adverse Events and Serious Adverse Events 
The investigator must make every effort to follow all AEs and SAEs regardless of attribution 
until judged resolved or stabilized, the subject is lost to follow-up, or it has been determined 
that treatment with study drug or participation in the study is not the cause of the AE or SAE. 
7.4 
Reporting Serious Adverse Events to the Sponsor and Institutional 
Review Board (IRB) or Ethics Committee (EC)  
The Sponsor or designee is under obligation to report certain SAEs to regulatory authorities 
related to investigational drugs in clinical trials. The Sponsor or designee must be notified 
within 24 hours of an AE when the investigator determines that an AE meets the protocol 
definition of an SAE, regardless of the cause or relationship to study drug.  
An SAE related to study participation occurring before study drug administration and after 
informed consent should be promptly reported to the Sponsor. If the investigator learns of 
any SAE at any time after a participant has been discharged from the study, and the SAE is 
considered likely related to study drug, the SAE should be promptly reported to the Sponsor. 
Please see the Safety Form Report Completion Instructions for safety reporting instructions.  
The investigator must also comply with applicable requirements concerning reporting of 
SAEs to the IRB or EC. This may include initial or follow-up notification of an SAE or other 
safety information. 
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7.5 
Reporting Serious Adverse Events to Regulatory Authorities and Study 
Investigators 
The Sponsor, or its designee, is responsible for submitting reports of serious, unexpected 
related adverse events to regulatory authorities on an expedited basis, according to the ICH 
E2A Guideline and to other regulatory authorities according to national and local regulations 
as required. The Sponsor, or its designee, is responsible for prompt submission to the IRB or 
EC of any expedited SAE reports submitted to regulatory authorities. All investigators 
participating in ongoing clinical studies with serlopitant will receive copies of the SAE 
reports submitted on an expedited basis to regulatory authorities. 
8 
STATISTICAL METHODS  
All statistical processing will be performed using SAS® unless otherwise stated. No interim 
analyses are planned. Data will be summarized with descriptive statistics by visit. For 
continuous variables, the following information will be presented: n, mean, standard 
deviation, median, minimum and maximum. For categorical variables, counts and 
percentages will be used. 
Baseline will be the last recorded value prior to the start of treatment.  
A SAP describing all statistical analyses will be written as a separate document. 
8.1 
Handling of Missing Data and Excluded Therapy Use  
Summary statistics will generally be reported based upon observed data. Should a 
determination of treatment period (on treatment, pre-treatment) be required for adverse 
events or concomitant medication but the corresponding date is missing, or is a partial date, 
the event/medication will be considered on treatment unless the portions of the date that are 
available indicate this is not possible. 
8.2 
Analysis Population  
All subjects who receive at least 1 confirmed dose of study drug and have at least 1 post-
baseline safety assessment will be included in the safety population. All analyses will be 
performed using the safety population.   
8.3 
Subject Disposition  
An accounting of all subjects by disposition will be presented. Subjects who discontinue 
study drug prematurely or withdraw from the study will be summarized and listed, with a 
description of the reason for early termination/withdrawal. 
8.4 
Subject Characteristics  
Demographic and other baseline characteristics will be summarized. 
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8.5 
Concomitant Medications  
Concomitant medications will be coded by the World Health Organization Drug Dictionary 
to Anatomical Therapeutic Classification (ATC) and preferred drug name. Concomitant 
medications will be summarized by ATC level and preferred drug name and listed. 
8.6 
Treatment Compliance and Extent of Exposure  
Compliance with study drug dosing will be determined based on tablet counts recorded on 
the eCRF. Compliance will be calculated by analyzing expected number of tablets returned 
versus actual number of tablets returned. Summaries of treatment exposure will also be 
produced.  
8.7 
Efficacy Analyses  
Descriptive statistics will be used to summarize the following: 
• Change from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52  
• Change from baseline in DLQI (symptoms and feelings, daily activities, leisure, work or 
school performance, personal relationships, and treatment) to Weeks 20, 36 and 52 
• Change from baseline in IGA PN-S to Weeks 4, 8, 20, 28, 36, 44, and 52.   
 
Data will be summarized by time point using frequency tabulations or descriptive statistics as 
appropriate. Observed results, as well as change from baseline will be summarized, as 
appropriate. 
8.8 
Safety Analyses  
8.8.1 
Adverse Events  
All AEs will be classified by system organ class and preferred term using the Medical 
Dictionary for Regulatory Activities (MedDRA). TEAEs will be tabulated in a manner which 
provides information about the incidence of TEAEs for the entire treatment period as well as 
by time period in order to understand the evolution of TEAEs over time. Thus, in addition to 
the TEAE analysis over the entire 12-month treatment time, results will be presented for the 
following periods: 0 to 4 weeks, > 4 to 12 weeks, > 12 to 28 weeks, > 28 weeks to 36 weeks, 
> 36 to end of treatment, and end of treatment to end of the study (including by weekly 
periods from end of treatment to end of study). For incidence reporting, if a subject reported 
more than one TEAE that was coded to the same system organ class or preferred term, the 
subject will be counted only once for that specific system organ class or preferred term. An 
overview of AEs, which includes subject incidence of AEs, TEAEs, treatment-related 
TEAEs, TEAEs by severity, SAEs, deaths, and AEs leading to discontinuation, will be 
presented.  
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All information pertaining to AEs noted during the study will be listed by subject and will 
include a verbatim description of the event as reported by the investigator, as well as the 
preferred term, system organ class, start date, end date (if ended), seriousness, severity, 
action taken regarding the study drug, outcome, and relationship to the study drug. In 
addition, a listing of subjects who prematurely discontinue from the study due to AEs will be 
provided. 
SAEs will be listed and summarized in a similar manner to AEs. 
8.8.2 
Clinical Safety Laboratory Results  
Clinical safety laboratory values will be measured by a central laboratory. Summary statistics 
for actual values and for changes from baseline will be tabulated for laboratory results by 
scheduled visit. Graphs of laboratory values over time will also be produced, and listings will 
be provided.  
Subjects with clinical laboratory values outside of the normal reference range at any post-
baseline assessment will be summarized. Shifts from baseline laboratory values will be 
tabulated. A listing of all out-of-range laboratory test results, including assessment of clinical 
significance, will also be provided. 
8.8.3 
Vital Signs  
The observed vital sign data and change from baseline for each scheduled visit will be 
summarized with descriptive statistics, and presented in a listing.  
8.8.4 
Electrocardiograms  
The overall ECG assessment (abnormal or normal) will be summarized and descriptively 
characterized, along with a summary of how many subjects developed a post treatment 
abnormal result.  
8.8.5 
Physical Exams  
Physical exam findings will be recorded by the sites within medical history or adverse events 
and otherwise not summarized, with the exception of weight and change from baseline in 
weight. 
8.8.6 
Menstrual Diaries 
Menstrual diary dates will be used to summarize number and duration of menses.  
8.8.7 
Hospital Anxiety and Depression Scale   
The observed data and change from baseline for the HADS will be summarized with 
descriptive statistics by scheduled visit. Both the Depression and the Anxiety subscales will 
be reported. 
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8.8.8 
Epworth Sleepiness Scale   
The observed data and change from baseline for the ESS will be summarized with descriptive 
statistics by scheduled visit.  
9 
ADMINISTRATIVE ASPECTS 
9.1 
Changes to the Protocol 
Protocol amendments must be made only with the prior written approval of the Sponsor. An 
investigator signature will be obtained for the initial protocol and any amendments. 
Substantial amendments will be provided to the appropriate regulatory authorities. No 
protocol changes affecting the following will be made without the written approval of the 
Sponsor and the responsible IRB or EC: 
• Safety and/or eligibility of subjects 
• Data integrity 
• Study design or conduct 
• Willingness of a subject to participate in the study 
9.2 
Study Termination 
The Sponsor has the right to terminate this study at any time. Reasons may include, but are 
not limited to, evidence of a potential safety risk in this study or other serlopitant studies or 
poor enrollment. The study may be terminated at the request of the US Food and Drug 
Administration, the European Medicines Agency, other Competent Authorities or regulatory 
agencies with appropriate jurisdiction, or if the approval to manufacture or to import study 
drug is revoked by those with jurisdiction. A written statement fully documenting the reasons 
for study termination will be provided to the IRB or EC. 
9.3 
Monitoring and Auditing Procedures 
The Sponsor will designate study monitors who will be responsible for monitoring the 
conduct of this study. A separate study Monitoring Plan will include details regarding the 
responsibilities of the study monitors, investigator responsibilities in providing access to 
records and addressing issues identified, the frequency and structure of monitoring visits, and 
adherence to subject confidentiality as outlined in the Informed Consent Form (ICF). 
9.4 
Transfer of Obligations 
The Sponsor will delegate certain aspects of study oversight to Contract Research 
Organizations (CROs). The specific responsibilities will be detailed in Transfer of 
Obligations documents.  
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9.5 
Informed Consent 
The purpose of the study, the procedures to be carried out, and any potential risks of study 
participation will be described in non-technical terms in the ICF. After having reviewed and 
understood the ICF, subjects will be required to read, sign, and date an IRB-approved or EC-
approved consent form before any study-specific procedures are carried out. Subjects will be 
assured that they may withdraw from the study at any time without jeopardizing medical care 
related to or required as a result of study participation. The original signed consent form will 
be maintained in the investigator site file. Copies of signed consent forms will be provided to 
the subject. 
9.6 
Communication with the Institutional Review Board or Ethics Committee 
The IRB or EC is constituted and operates in accordance with the principles and 
requirements described in the ICH E6(R2) guideline. The protocol, ICF, other written subject 
information, and any proposed study advertising material must be submitted to the IRB or 
EC for written approval. IRB or EC approval of these documents will be provided to the 
investigator. The study will not start until the IRB or EC has granted its approval of the study 
materials and procedures. 
Protocol amendments will be submitted to the IRB or EC as explained in Section 9.1. SAE 
information will be submitted to the IRB or EC as explained in Section 7.4.  
If the study is terminated by the Sponsor, a written statement fully documenting the reason(s) 
for study termination will be provided to the IRB or EC. 
9.7 
Disclosure and Confidentiality 
By signing this protocol, the investigator agrees to keep all information provided by the 
Sponsor in strict confidence and to require the same confidentiality from site staff and the 
IRB or EC. Study documents provided by the Sponsor (e.g. protocol, Investigator Brochure, 
eCRFs) will be stored appropriately to ensure their confidentiality. The information provided 
by the Sponsor to the investigator may not be disclosed to others without direct written 
authorization from the Sponsor, except to the extent necessary to obtain informed consent 
from subjects who wish to participate in the study.  
The investigator must ensure that the subjects be identified by a unique subject study 
number. Other study-related documents that may contain confidential participant information 
(e.g. signed ICFs) will be kept in strict confidence by the investigator and be stored in a 
secure location with access restricted to the study staff. 
9.8 
Records and Electronic Case Report Forms 
All study data except central laboratory and ECG data will be recorded in an eCRF system. 
Data will be entered at the site by the appropriately designated and trained site personnel. All 
source documents from which eCRF entries are derived should be placed in the subject’s 
medical records. eCRFs will be completed for every subject screened in the study. The 
investigator/institution should maintain adequate and accurate source documents and trial 
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records that include all pertinent observations on each of the site’s trial subjects. Source data 
should 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 (e.g., via an audit trail). 
The study monitor will review all eCRFs in detail and will have access to participant medical 
records, laboratory data, and other source documentation to allow required eCRF fields to be 
verified by source data. 
Data consistency and plausibility checks against data entered into the eCRF will be included 
in the eCRF system. Data corrections can be performed in the eCRFs by the site. For each 
instance of data modification, the system requires a reason for change. The system keeps a 
full audit trail of the data values, the date and time of modification, and the electronic 
signature of the user who performed the change. 
After a full review of the eCRFs by the study monitor and resolution of any data 
clarifications, the investigator will review, sign, and approve the subject’s eCRF. All 
essential documents, source data, clinical records, and laboratory data will be retained by the 
site in accordance with the ICH E6(R2) guideline and the site’s data retention policies. These 
records must be available for inspection by the Sponsor, monitor, and regulatory authorities. 
Furthermore, the investigators/institutions will permit trial-related monitoring, audits, EC 
review, and inspections by a competent authority as necessary and provide direct access to 
source data/documents. 
Further detail regarding data management and eCRFs is included in the Data Management 
Plan. 
9.9 
Good Clinical Practice and Ethical Study Conduct 
The study procedures outlined in this protocol will be conducted in accordance with 
applicable ICH Guidelines, including ICH E6(R2): Good Clinical Practice. As this study is 
conducted under a US IND, the investigator will also ensure that the basic principles of 
“Good Clinical Practice”, as outlined in 21 CFR 312, subpart D, “Responsibilities of 
Sponsors and Investigators”, 21 CFR, part 50 and 21 CFR, part 56 are adhered to. 
The study procedures outlined in this protocol will also be conducted in accordance with the 
principles of the Declaration of Helsinki. 
9.10 
End of Study Notification 
The Sponsor will notify appropriate regulatory authorities and the IRB or EC within 90 days 
from the end of the clinical study. The end of the clinical study is defined as the last study 
visit for the last subject. 
9.11 
Publication of Results 
All publications (e.g. manuscripts, abstracts, oral/slide presentations, book chapters) based on 
this study or relying on data from this study must be submitted to the Sponsor for review and 
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release before submission for publication. The Sponsor is responsible for final approval of all 
publications. 
9.12 
Final Report 
A clinical trial summary report will be provided to the appropriate regulatory authorities 
within one year of the end of the clinical study. 
 
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10 
REFERENCES  
Akiyama T, Nguyen T, Curtis E, et al. A central role for spinal dorsal horn neurons that 
express neurokinin-1 receptors in chronic itch. Pain. 2015;156(7):1240-6. 
Andoh T NT, Satoh M, Kuraishi Y. Substance P induction of itch-associated response 
mediated by cutaneous NK1 tachykinin receptors in mice. J Pharmacol Exp Ther. 
1998;286(3):1140-1145. 
Booken N, Heck M, Nicolay JP, et al. Oral aprepitant in the therapy of refractory pruritus in 
erythrodermic cutaneous T-cell lymphoma. Br J Dermatol. 2011;164(3):665-67. 
Carstens EE, Akiyama T. Central mechanisms of itch. Curr Probl Dermatol. 2016;50:11-17. 
Chuquilin M, Yazan Alghalith, Fernandez KH. Neurocutaneous disease: Cutaneous 
neuroanatomy and mechanisms of itch and pain. J Am Acad Dermatol. 
2016;74:197-212.  
Common Terminology Criteria for Adverse Events (CTCAE). 4.03 ed: National Institutes of 
Health; 2010. 
Duval A, Dubertret L. Aprepitant as an antipruritic agent? N Eng J Med. 
2009;361:1415-1416. 
El-Nour H, Lundeberg L, Al-Tawil R, et al. Upregulation of the axonal growth and the 
expression of substance P and its NK1 receptor in human allergic contact dermatitis. 
Immunopharmacol Immunotoxicol. 2006;28(4):621-631. 
Emend® (aprepitant) capsule for oral use. U.S. Prescribing Information. Merck Sharp and 
Dohme Corp. Revised August 2015. 
Examples of clinical inhibitors for P450-mediated metabolisms (for concomitant use clinical 
DDI studies and/or drug labeling) (9/26/2016). U.S. Food and Drug Administration; 
2016. 
Gerber PA, Buhren BA, Cevikbas F, et al. Preliminary evidence for a role of mast cells in 
epidermal growth factor receptor inhibitor-induced pruritus. J Am Acad Dermatol. 
2010;63(1):163-165. 
Harrison S GP. Substance P. Int J Biochem. 2001;33(6):555-576. 
Hökfelt T PB, Wahren J. Substance P: A pioneer amongst neuropeptides. J Intern Med 2001; 
249:27–40. 
Ikoma A, Steinhoff M, Ständer S, et al. The neurobiology of itch. Nat Rev Neurosci. 
2006;7:535-547. 
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Lotts T, Ständer S. Research in practice: substance P antagonism in chronic pruritus. J Dtsch 
Dermatol Ges. 2014;12(7):557-559. 
Luo J, Feng J, Liu S, et al. Molecular and cellular mechanisms that initiate pain and itch. Cell 
Mol Life Sci 2015;72:3201-23. 
M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing 
Authorization for Pharmaceuticals. Food and Drug Administration; 2010. 
Recommendations related to contraception and pregnancy testing in clinical trials. Clinical 
Trial Facilitation Group; 2014. 
Santini D, Vincenzi B, Guida FM, et al. Aprepitant for management of severe pruritus related 
to biological cancer treatments: a pilot study. Lancet Oncol. 2012;13(10):1020-1024. 
Schmelz M. Itch and pain differences and commonalities. In: Schaible HG. (eds) Pain 
Control. Handbook of Experimental Pharmacology, 2015;227:285-301.   
Ständer S, Siepmann D, Herrgott I, et al. Targeting the neurokinin receptor 1 with aprepitant: 
a novel antipruritic strategy. Plos One. 2010;5(6):e10968.   
Ständer S, Weisshaar E, Raap U. Emerging drugs for the treatment of pruritus. Exp Opin 
Emerg Drugs. 2015;20:515-21. 
Steinhoff M, Bienenstock J, Schmelz M, et al. Neurophysiological, neuroimmunological, and 
neuroendocrine basis of pruritus. J Invest Dermatol. 2006;126:1705-18. 
Steinhoff MS, von Mentzer B, Geppetti P, et al. Tachykinins and their receptors: 
contributions to physiological control and the mechanisms of disease. Physiol Rev. 
2014;94(1):265-301. 
Torres T, Fernandes I, Selores M, et al. Aprepitant: Evidence of its effectiveness in patients 
with refractory pruritus continues. J Am Acad Dermatol. 2012;66(1):e14-15. 
U.S. Medical Eligibility Criteria for Contraceptive Use, 2010. Vol 20172010. 
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APPENDIX A 
SCHEDULE OF ACTIVITIES AND ASSESSMENTS 
Examination 
Base-
line1 
Week 
4 (±7 
days) 
Week 
8 (±7 
days) 
Week 
12 (±7 
days) 
Week 
20 (±7 
days) 
Week 
28 (±7 
days) 
Week 
36 (±7 
days) 
Week 
44 (±7 
days) 
Week 
52 (±7 
days) 
ETD2 
Post-drug observation: 
3 days (±1 day), and 7, 14, 
21, and 28 days (±3 days) 
after Week 52 Visit 
Post-drug 
observation: 
35 days (±3 days) 
after Week 52 Visit 
Informed consent 
X 
I/E criteria 
X 
Demographics/ 
Medical History 
X 
Physical exam3 
X4 
X 
X 
X4 
X 
X4 
X 
X 
X4 
X4 
X4 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Labs5 
X1 
X 
X 
X 
X 
X 
X 
Urine pregnancy test6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
X 
X 
X 
X 
X 
X 
WI-NRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IGA PN-S (PN subjects) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
DLQI 
X 
X 
X 
X 
X 
HADS, ESS 
X 
X 
X 
X 
X 
X 
X 
Photographs (if applicable) 
X 
X 
X 
X 
X 
Dispense/review menstrual 
diary (if applicable) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense/collect 
serlopitant 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Review study drug 
compliance 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs/SAEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1
Baseline may coincide with the final visit of prior applicable study; Baseline labs do not need to be repeated if completed within prior 14 days 
2
Early Treatment Discontinuation 
3
Baseline physical exam is complete; all other physical exams are targeted 
4
Height/weight at Baseline and weight at Weeks 12, 28, 52 and ETD/post-drug observation 35 days after Week 52  
5
Labs are ideally performed in the morning, particularly at visits with endocrine assessments (Baseline, Weeks 12, 28 and 52).  Hematology and Chemistry at Baseline, 
Weeks 4, 12, 28, 52, and ETD/ post-drug observation 35 days after Week 52; Reproductive Endocrinology at Baseline, Weeks 28 and 52 (females under 55 years of age 
at consent) 
6
For females of childbearing potential (with positive or equivocal results to be confirmed by a serum pregnancy test). Monthly pregnancy testing can be performed in 
between visits (and recorded as an Unscheduled visit), and at any time per the investigator’s discretion. 
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APPENDIX B  
LIST OF STRONG CYP3A4 INHIBITORS   
The list of strong CYP3A4 inhibitors is based on the United States Food and Drug 
Administration (FDA) list effective September 26, 2016, Examples of clinical inhibitors for 
P450-mediated metabolisms (for concomitant use clinical DDI studies and/or drug labeling 
(“Examples of clinical inhibitors for P450-mediated metabolisms (for concomitant use clinical 
DDI studies and/or drug labeling (9/26/2016)”).  
Note: This Appendix may be replaced if applicable (e.g., if updated by the FDA) through site 
communications without requiring a protocol amendment. 
1. 
boceprevir 
2. 
clarithromycin 
3. 
cobicistat 
4. 
conivaptan 
5. 
danoprevir and ritonavir 
6. 
diltiazem 
7. 
elvitegravir and ritonavir 
8. 
idelalisib 
9. 
indinavir and ritonavir 
10. 
itraconazolea 
11. 
ketoconazolea 
12. 
lopinavir and ritonavir 
13. 
nefazodone 
14. 
nelfinavir 
15. 
paritaprevir and ritonavir and (ombitasvir and/or dasabuvir) 
16. 
posaconazolea 
17. 
ritonavir 
18. 
saquinavir and ritonavir 
19. 
telaprevir 
20. 
tipranavir and ritonavir 
21. 
troleandomycin 
22. 
voriconazolea 
23. 
regular grapefruit juice consumption (note: The effect of grapefruit juice varies 
widely among brands and is concentration-, dose-, and preparation-dependent. 
Grapefruit juice may be a strong or a moderate CYP3A inhibitor depending on the 
preparation)b 
 
a 
When administered topically, it may not be considered a strong CYP3A4 inhibitor due to limited systemic 
absorption. 
b 
The occasional consumption of grapefruit juice or the consumption of grapefruit or other citrus fruits (e.g., 
pomelo, lemon, lime, Seville orange, bitter orange, starfruit) is not contraindicated. 
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APPENDIX C  
WORST ITCH NUMERIC RATING SCALE QUESTIONNAIRE 
c 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
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APPENDIX D 
INVESTIGATOR’S GLOBAL ASSESSMENT OF PRURIGO 
NODULARIS: STAGE 
Score 
Category 
Description: Stage (IGA PN-S) 
0 
Clear 
No nodules (0 nodules) 
1 
Almost 
Clear 
Rare, flattened lesions, with no more than 5 dome-shaped palpable nodules 
(approximately 1-5 nodules) 
2 
Mild 
Few, mostly flattened lesions, with small number of dome-shaped palpable 
nodules (approximately 6-19 nodules) 
3 
Moderate 
Many lesions, partially flattened, and dome-shaped palpable nodules 
(approximately 20-100 nodules) 
4 
Severe 
Abundant lesions, majority are dome-shaped palpable nodules (over 
100 nodules) 
 
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APPENDIX E 
DERMATOLOGY LIFE QUALITY INDEX 
Different language versions may be used. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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APPENDIX F 
HOSPITAL ANXIETY AND DEPRESSION SCALE 
 
 
To be used under license. 
  
 
  
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
   
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
  
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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APPENDIX G 
EPWORTH SLEEPINESS SCALE 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
  
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
  
 
  
 
  
 
  
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
218


 
1 
CLINICAL STUDY PROTOCOL MTI-107 
SUMMARY OF CHANGES 
 
Drug Product Name: 
Serlopitant 
 
Study Title:  
AN OPEN-LABEL LONG-TERM SAFETY STUDY OF 
SERLOPITANT FOR THE TREATMENT OF PRURITUS 
IND No.: 
 
 
117780 
EudraCT No.:  
 
2017-004211-40 
ClinicalTrials.gov ID:  
NCT03540160 
Protocol Version: 
 
3.0 
Protocol Date: 
 
21 March 2019 
Replaces Version/Date: 
2.0 / 03 July 2018 
 
219


Serlopitant 
 
Menlo Therapeutics Inc. 
MTI-107 Protocol, Summary of Changes Version 2.0 to Version 3.0 
 
 
 
2 
The following changes were made to the MTI-107 Clinical Study Protocol from Version 2.0 to Version 3.0. 
KEY CHANGES: 
Section(s) 
Summary of Change 
Reason for Change 
Synopsis 
Changed number of patients from 400 to 700 
Permits enrollment of additional eligible patients 
4.1 Study Population 
Changed number of patients from 400 to 700 
Permits enrollment of additional eligible patients 
 
ADMINISTRATIVE CHANGES: 
Section(s) 
Summary of Change 
Title page 
Updated protocol version number and release date 
Signature Page for Investigator(s)   
Updated protocol version number and release date 
Sponsor Protocol Approval Signature(s) 
Updated protocol version number 
Throughout  
Updated protocol version in footer; Edited formatting and corrected minor typos and 
inconsistencies 
 
220

SAP_001.pdf: 
Protocol: MTI-107 
Confidential - Proprietary Information 

Protocol number: MTI-107 

Document title: An open-label long-term safety study of serlopitant for the 
treatment of pruritus. 

Version numbers: SAP Version 4.0 

Date of the documents: 12 May 2020 

NCT number: NCT03540160 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 1 
Protocol Number: MTI-107  
12 May 2020 
STATISTICAL ANALYSIS PLAN 
Protocol Number: 
MTI-107 
 
 
Study Title: 
AN OPEN-LABEL LONG-TERM SAFETY 
STUDY OF SERLOPITANT FOR THE 
TREATMENT OF PRURITUS 
 
 
Development Phase of Study: 
Phase 3 
 
 
Sponsor: 
Menlo Therapeutics Inc. 
200 Cardinal Way, 2nd Floor 
Redwood City, CA 94063 
USA 
Sponsor Contact: 
 
 
 
Statistical Analysis Plan based on 
Protocol Version: 
Version 3.0, 21 March 2019 
 
 
Statistical Analysis Plan Date: 
12 May 2020 
Statistical Analysis Plan Version: 
Version 4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confidentiality Statement: 
This document is a confidential communication of Menlo Therapeutics Inc. As such, the recipients agree not to 
disclose or reproduce, without prior written approval, this document and any attachments, except to appropriate 
Institutional Review Boards, Ethics Committees, representatives of the US Food and Drug Administration, other 
regulatory agencies or as otherwise required by applicable laws or regulations. 
 
 
PPD




 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 3 
Protocol Number: MTI-107  
12 May 2020 
TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ....................................6 
2. 
INTRODUCTION .................................................................................................................6 
3. 
STUDY OBJECTIVES .........................................................................................................6 
4. 
STUDY DESIGN ...................................................................................................................7 
4.1 Overall Study Design ......................................................................................................7 
4.1.1 
Schedule of Visits and Assessments .................................................................7 
4.1.2 
Method of Assigning Subjects to Treatment Groups ........................................7 
4.1.3 
Blinding .............................................................................................................7 
5. 
EFFICACY AND SAFETY ENDPOINTS .........................................................................7 
5.1 Efficacy Endpoints ..........................................................................................................7 
5.2 Safety Endpoints .............................................................................................................8 
6. 
STATISTICAL AND ANALYTICAL PLANS ..................................................................8 
6.1 General Methodology .....................................................................................................8 
6.1.1 
Statistical Analysis ............................................................................................8 
6.1.2 
Baseline Definition ............................................................................................8 
6.1.3 
Visit Windowing ...............................................................................................9 
6.1.4 
Adjustments for Covariates ...............................................................................9 
6.1.5 
Handling of Dropouts or Missing Data .............................................................9 
6.1.6 
Multicenter Studies ............................................................................................9 
6.1.7 
Multiple Comparisons/Multiplicity ...................................................................9 
6.1.8 
Examination of Subgroups ................................................................................9 
6.2 Disposition of Subjects ...................................................................................................9 
6.3 Protocol Deviations .........................................................................................................9 
6.4 Data Sets Analyzed .......................................................................................................10 
6.4.1 
Safety Population ............................................................................................10 
6.5 Demographic and Other Baseline Characteristics ........................................................10 
6.6 Prior and Concomitant Medications .............................................................................10 
6.7 Analysis of Efficacy ......................................................................................................10 
6.8 Safety Evaluation ..........................................................................................................10 
6.8.1 
Extent of Exposure ..........................................................................................10 
6.8.2 
Adverse Events ................................................................................................10 
6.8.3 
Clinical Laboratory Evaluation .......................................................................11 
6.8.4 
Other Observations Related to Safety .............................................................11 
6.8.4.1 
Electrocardiogram Measurements ...............................................11 


 
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6.8.4.2 
Vital Signs ....................................................................................11 
6.8.4.3 
Physical Exams ............................................................................11 
6.8.4.4 
Menstrual Diaries .........................................................................11 
6.8.4.5 
Hospital Anxiety and Depression Scale (HADS) ........................11 
6.8.4.6 
Epworth Sleepiness Scale (ESS) ..................................................11 
7. 
DETERMINATION OF SAMPLE SIZE .........................................................................12 
8. 
CHANGES IN THE PLANNED ANALYSES..................................................................12 
9. 
INDEX OF PLANNED END-OF-TEXT TABLES AND FIGURES .............................13 
10. INDEX OF PLANNED LISTINGS ...................................................................................27 
 
 
 


 
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Revision History: 
 Version  
Date 
Summary of Changes 
Author 
Version 1 
13 November 2018 Original document 
 
Version 2 
03 April 2019 
Updated title page to reflect current 
version of protocol.  Updated SAP 
version and date. 
Updated Section 7 to include expected 
number of subjects to be enrolled. 
 
Version 3 
11 February 2020 
Updated SAP version and date. 
Editorial and grammatical updates 
including abbreviations and references. 
Added table, figure and listing shells. 
 
Version 4 
12 May 2020 
Updated SAP version and date. 
Updated SAP throughout, including 
text, table shells and listing shells to 
facilitate abbreviated study report. 
 
 
 
PPD
PPD
PPD
PPD


 
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1. LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AD 
Atopic Dermatitis 
AE(s) 
Adverse event(s) 
DLQI 
Dermatology Life Quality Index 
ECG 
Electrocardiogram 
EOS 
End of Study 
EOT 
End of Treatment 
ESS 
Epworth Sleepiness Scale 
HADS 
Hospital Anxiety and Depression Scale 
IGA PN-S 
Investigator’s Global Assessment of Prurigo Nodularis Stage 
MedDRA 
Medical Dictionary for Regulatory Activities 
PN 
Prurigo Nodularis 
SAE(s) 
Serious adverse event(s) 
SAS® 
Statistical Analysis System (SAS® Institute Inc., Cary, NC) 
TEAE(s) 
Treatment-emergent adverse event(s) 
WHO-DD 
World Health Organization Drug Dictionary 
WI-NRS 
Worst-Itch Numeric Rating Scale 
2. INTRODUCTION 
The MTI-107 study described herein is an open-label study to assess the long-term safety of 
serlopitant in adults with pruritus associated with prurigo nodularis (PN), atopic dermatitis (AD), 
or psoriasis. 
Subjects enrolled in MTI-107 may have or may not have participated in previous Menlo 
Therapeutics Inc. studies. Previous study participation includes studies in PN (MTI-105, MTI-
106, TCP-102), in AD (MTI-103) and in psoriasis (MTI-109).  
The MTI-107 study has been terminated early by Sponsor. The Statistical Analysis Plan has been 
updated to facilitate an abbreviated clinical study report. 
3. STUDY OBJECTIVES 
The primary objective of this study is to assess the long-term safety of serlopitant in adults with 
pruritus associated with PN, AD, or psoriasis. 
The secondary objectives of this study are to assess the change in severity of pruritus in subjects 
with PN, AD, or psoriasis using the worst-itch numeric rating scale (WI-NRS); to assess the 
change in severity and extent of PN using the Investigator’s Global Assessment of PN Stage 


 
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(IGA PN-S), for those subjects with PN; and to assess whether serlopitant produces physical 
dependence. 
4. STUDY DESIGN 
4.1 
Overall Study Design 
This is a multicenter, open-label study to assess the long-term safety of serlopitant in adults with 
pruritus associated with PN, AD, or psoriasis. Eligible subjects who have completed selected 
studies of serlopitant may be given the opportunity, at the Investigator’s discretion, to consent to 
and participate in this open-label study, regardless of their treatment allocation in prior studies. If 
deemed necessary by Menlo Therapeutics to meet enrollment objectives, eligible subjects who 
have not participated in a prior serlopitant study may also be enrolled in study MTI-107. 
Approximately 120 study sites may enroll subjects in this long-term safety study. 
This study will consist of two periods, for a total study period of 57 weeks: 
• Treatment period: 52 weeks 
• Post-drug observation period: 5 weeks 
4.1.1 
Schedule of Visits and Assessments 
The schedule of assessments can be found in Section 6.4 and Appendix A of the Protocol.  
4.1.2 
Method of Assigning Subjects to Treatment Groups 
This is an open-label single-arm study. Eligible subjects will receive serlopitant 5 mg tablets. 
4.1.3 
Blinding 
This is an open-label study. 
5. EFFICACY AND SAFETY ENDPOINTS 
5.1 
Efficacy Endpoints 
Efficacy endpoints are as follows: 
• Change from baseline in WI-NRS to Weeks 4, 8, 20, 28, 36, 44, and 52 
• Change from baseline in Dermatology Life Quality Index (DLQI) to Weeks 20, 36, and 
52 
• Change from baseline in Investigator’s Global Assessment of PN Stage (IGA PN-S) to 
Weeks 4, 8, 20, 28, 36, 44, and 52 


 
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5.2 
Safety Endpoints 
Safety endpoints include the following: 
• Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events 
(SAEs) 
• Changes from baseline in clinical laboratory parameters 
• Changes from baseline in vital sign and electrocardiogram (ECG) parameters  
• Change from baseline in the Hospital Anxiety and Depression Scale (HADS) 
• Change from baseline in the Epworth Sleepiness Scale (ESS) 
• Assessment of physical dependence following chronic study drug exposure, in the 
monitored 5-week post-drug discontinuation period 
6. STATISTICAL AND ANALYTICAL PLANS 
6.1 
General Methodology 
All statistical processing will be performed using SAS® Version 9.3 or later, unless otherwise 
stated. No interim analyses are planned. Endpoints will be summarized with descriptive statistics 
by visit. For continuous variables, the following information will be presented: n (number of 
subjects), mean, standard deviation (SD), median, minimum and maximum. For categorical 
variables, counts and percentages will be presented. 
Reported adverse events (AEs), medical history, and prior and concomitant procedures and 
therapies will be classified on the basis of Medical Dictionary for Regulatory Activities 
(MedDRA) terminology. Concomitant medications will be classified on the basis of World 
Health Organization Drug Dictionary (WHO-DD) terminology. 
6.1.1 
Statistical Analysis 
All summary tables and data listings will be prepared by QST Consultations, Ltd., utilizing 
SAS® Version 9.3 or later software.  
The standard operating procedures of QST Consultations, Ltd. will be followed in the creation 
and quality control of all data displays. 
6.1.2 
Baseline Definition 
No change from baseline summaries will be created. 


 
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6.1.3 
Visit Windowing 
Data will be provided in by-subject listings based on nominal visit indications. 
  
6.1.4 
Adjustments for Covariates 
No inferential statistical analyses are planned. 
6.1.5 
Handling of Dropouts or Missing Data 
Summary statistics will generally be reported based upon observed data. Should a determination 
of treatment period (on treatment, pre-treatment, post-treatment) be required for AEs or 
concomitant medication but the corresponding date is missing, or is a partial date, the 
event/medication will be considered on treatment unless the portions of the date that are 
available indicate this is not possible.        
6.1.6 
Multicenter Studies 
The clinical study will be conducted under a common protocol for each investigational site with 
the intention of pooling all the data for summaries. Every effort will be made to promote 
consistency in study execution at each study site. 
6.1.7 
Multiple Comparisons/Multiplicity 
No inferential statistical analyses are planned. 
6.1.8 
Examination of Subgroups 
No subgroup summaries will be created. 
6.2 
Disposition of Subjects 
An accounting of all enrolled subjects by disposition will be presented. Subjects who discontinue 
study drug prematurely or withdraw from the study will be summarized and listed, with a 
description of the reason for early termination/withdrawal. 
The number of subjects included in the safety population will be summarized. Subjects who are 
excluded from the safety population will be summarized by the reasons for exclusion. 
6.3 
Protocol Deviations 
Protocol deviations will be presented in a data listing.  


 
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6.4 
Data Sets Analyzed 
6.4.1 
Safety Population 
All subjects who receive at least 1 confirmed dose of study drug and have at least 1 post-baseline 
safety assessment or a reported TEAE will be included in the safety population. All analyses will 
be performed using the safety population. 
6.5 
Demographic and Other Baseline Characteristics 
Sex, race, and ethnicity will be summarized by counts and percentages. Age, height (cm), and 
weight (kg) will be summarized with descriptive statistics. 
Medical histories will be coded using MedDRA and presented in a by-subject listing. 
Disease history (PN, AD, psoriasis) will be presented in a by-subject listing. 
6.6 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded by the WHO-DD to Anatomical Therapeutic 
Classification (ATC) and preferred drug name.  
A by-subject listing of all prior and concomitant medications will be presented.  The associated 
by-subject listing will have a prior/concomitant determination that is based on the date of first 
dose. 
6.7 
Analysis of Efficacy 
Efficacy data will be provided in by-subject listings. 
6.8 
Safety Evaluation 
6.8.1 
Extent of Exposure 
The extent of exposure to study drug will be summarized by days with exposure and total 
number of tablets used. Subjects will be considered having 6-Month exposure if the date of first 
dose – date of last dose + 1 is greater than or equal to 182 days. Subjects will be considered 
having 1-Year exposure if date of first dose – date of last dose + 1 is greater than or equal to 358 
days, considering the allowable -7 day window for the Week 52 visit. 
6.8.2 
Adverse Events 
All AEs will be classified by system organ class and preferred term using the MedDRA. TEAEs 
will be tabulated in a manner which provides information about the incidence of TEAEs for the 
entire study. For incidence reporting, if a subject reported more than one TEAE that was coded 
to the same system organ class or preferred term, the subject will be counted only once for that 


 
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specific system organ class or preferred term. An overview of AEs, which includes subject 
incidence of AEs, TEAEs, treatment-related TEAEs, TEAEs by severity, SAEs, deaths, and AEs 
leading to discontinuation of study drug, will be presented. 
All information pertaining to AEs noted during the study will be listed by subject and will 
include a verbatim description of the event as reported by the investigator, as well as the 
preferred term, system organ class, start date, end date (if ended), seriousness, severity, action 
taken regarding the study drug, outcome, and relationship to the study drug. In addition, a listing 
of subjects who prematurely discontinued study drug due to AEs will be provided. 
SAEs will be listed and summarized in a similar manner to AEs. 
6.8.3 
Clinical Laboratory Evaluation 
By-subject listings of all laboratory data, as well as abnormal laboratory results, will be 
presented. Clinically significant laboratory results will be recorded as an AE.  
6.8.4 
Other Observations Related to Safety 
6.8.4.1 
Electrocardiogram Measurements 
Data will be provided in a by-subject listing. 
6.8.4.2 
Vital Signs 
Data will be provided in a by-subject listing. 
6.8.4.3 
Physical Exams 
Clinically significant physical exam findings will be recorded by the sites within medical history 
or adverse events and otherwise not summarized. Data will be provided in a by-subject listing. 
6.8.4.4 
Menstrual Diaries 
Data will be provided in a by-subject listing. 
6.8.4.5 
Hospital Anxiety and Depression Scale (HADS) 
Data will be provided in a by-subject listing. 
6.8.4.6 
Epworth Sleepiness Scale (ESS) 
Data will be provided in a by-subject listing. 


 
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7. DETERMINATION OF SAMPLE SIZE 
No formal sample size calculations were performed. Up to 700 adult subjects with pruritus 
associated with PN, AD, or psoriasis will be enrolled in this study. 
8. CHANGES IN THE PLANNED ANALYSES 
No graphs of laboratory values over time will be created. 
 
Planned analyses have been updated to facilitate an abbreviated clinical study report.  
 
 


 
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9. 
INDEX OF PLANNED END-OF-TEXT TABLES AND FIGURES 
Table 14.0.1.1: Summary of Subject Completion/Discontinuation (Enrolled Subjects) ...............14 
Table 14.0.2.1: Summary of Subjects Excluded from Analyses  (Enrolled Subjects) ..................15 
Table 14.1.1.1: Summary of Subject Demographics  (Safety Population) ....................................16 
Table 14.3.0.1: Summary of Extent of Exposure (Safety Population) ..........................................18 
Table 14.3.1.1.1.1: Overall Summary of Treatment-Emergent Adverse Events (TEAEs) (Safety 
Population) ............................................................................................19 
Table 14.3.1.1.2.1: Summary of Subjects Reporting Treatment-Emergent Adverse Events 
(TEAEs) by MedDRA System Organ Class and Preferred Term (Safety 
Population) ............................................................................................20 
Table 14.3.1.1.3.1: Summary of Treatment-Emergent Adverse Events (TEAEs) Leading to 
Discontinuation of Study Drug (Safety Population) .............................21 
Table 14.3.1.1.4.1: Summary of Subjects Reporting Treatment-Emergent Adverse Events 
(TEAEs) by Severity (Safety Population) .............................................22 
Table 14.3.1.1.5.1: Summary of Subjects Reporting Treatment-Emergent Adverse Events 
(TEAEs) by Relationship to Study Drug (Safety Population) ..............23 
Table 14.3.1.3.1.1: Summary of Subjects Reporting Serious Treatment-Emergent Adverse 
Events (TEAEs) by  MedDRA System Organ Class and Preferred Term 
(Safety Population)................................................................................24 
Table 14.3.1.3.2.1: Summary of Subjects Reporting Serious Treatment-Emergent Adverse 
Events (TEAEs) by Severity (Safety Population) .................................25 
Table 14.3.1.3.3.1: Summary of Subjects Reporting Serious Treatment-Emergent Adverse 
Events (TEAEs) by Relationship to Study Drug (Safety Population) ..26 


 
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Table 14.0.1.1: Summary of Subject Completion/Discontinuation 
(Enrolled Subjects) 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Completed Treatment 
Yes 
xx ( xx.x%) 
No 
xx ( xx.x%) 
Reason for Discontinuation from Treatment 
Adverse Event 
xx ( xx.x%) 
Lack of Efficacy 
xx ( xx.x%) 
Pregnancy  
xx ( xx.x%) 
Investigator Decision 
xx ( xx.x%) 
Withdrawal by Subject from Treatment 
xx ( xx.x%) 
Protocol Deviation 
xx ( xx.x%) 
Sponsor Decision 
xx ( xx.x%) 
Other 
xx ( xx.x%) 
Completed Follow-up 
Yes 
xx ( xx.x%) 
No 
xx ( xx.x%) 
Reason for Discontinuation from Follow-up 
Withdrawal by Subject from Study 
xx ( xx.x%) 
Lost to Follow-up  
xx ( xx.x%) 
Other 
xx ( xx.x%) 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 


 
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Table 14.0.2.1: Summary of Subjects Excluded from Analyses  
(Enrolled Subjects) 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Safety Population 
Number of Subjects Included 
xx ( xx.x%) 
Number of Subjects Excluded 
xx ( xx.x%) 
Reason for Exclusion 
No Evidence of Subject Dosing 
xx ( xx.x%) 
No Post-Baseline Assessment/TEAE 
xx ( xx.x%) 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 
 
 
 
 


 
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Table 14.1.1.1: Summary of Subject Demographics  
(Safety Population) 
(Page 1 of 2) 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Age (years) 
n 
xxx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
Sex 
n 
xxx  
Male 
xx ( xx.x%) 
Female 
xx ( xx.x%) 
Ethnicity 
n 
xxx  
Hispanic or Latino 
xx ( xx.x%) 
Not Hispanic or Latino 
xx ( xx.x%) 
Race 
n 
xxx  
American Indian or Alaska Native 
xx ( xx.x%) 
Asian 
xx ( xx.x%) 
Black or African American 
xx ( xx.x%) 
Native Hawaiian or Other Pacific Islander 
xx ( xx.x%) 
White 
xx ( xx.x%) 
Multiple/Other 
xx ( xx.x%) 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
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Table 14.1.1.1: Summary of Subject Demographics  
(Safety Population) 
(Page 2 of 2) 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Height (cm) 
N 
xxx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
Weight (kg) 
n 
xxx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 
 
 
 
 
 
 


 
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Table 14.3.0.1: Summary of Extent of Exposure 
(Safety Population) 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Total Number of Tablets Used 
xxx 
n 
xxx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
Total Number of Days of Exposure 
xxx 
n 
xxx 
Mean 
xx.x 
SD 
xx.xx 
Median 
xx.x 
Min. to Max. 
xx to xx 
Subjects with 6-Month Exposurea 
xx ( xx.x%) 
Subjects with 1-Year Exposurea 
xx ( xx.x%) 
 
 
a Subjects considered having 6-Month exposure if date of first dose – date of last dose + 1 is greater than or equal to 182 days. 
Subjects considered having 1-Year exposure if date of first dose – date of last dose + 1 is greater than or equal to 358 days, considering the allowable -7 day 
window for the Week 52 visit. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 


 
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Table 14.3.1.1.1.1: Overall Summary of Treatment-Emergent Adverse Events (TEAEs) 
(Safety Population) 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Subjects with any TEAE 
xx ( xx.x%) 
Number of TEAEs 
xxx  
Subjects with any Related TEAE 
xx ( xx.x%) 
Number of Related TEAEs 
xxx  
Subjects with any Serious TEAE 
xx ( xx.x%) 
Number of Serious TEAEs 
xxx  
Subjects with any Related Serious TEAE 
xx ( xx.x%) 
Number of Related Serious TEAEs 
xxx  
Subjects who Died 
xx ( xx.x%) 
Subjects who Discontinued Study Drug Due to TEAE 
xx ( xx.x%) 
Maximum Severity by Subject 
 Grade 5  
xx ( xx.x%) 
Grade 4 
xx ( xx.x%) 
Grade 3 
xx ( xx.x%) 
Grade 2  
xx ( xx.x%) 
Grade 1  
xx ( xx.x%) 
Maximum Relationship by Subject 
 Likely Related  
xx ( xx.x%) 
Likely Unrelated 
xx ( xx.x%) 
 
 
Note:  TEAEs are AEs with an onset after first dose of study drug.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 


 
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Table 14.3.1.1.2.1: Summary of Subjects Reporting Treatment-Emergent Adverse Events (TEAEs) by MedDRA System Organ Class and Preferred Term 
(Safety Population) 
(Page 1 of xx) 
 
System Organ Classa 
Preferred Term 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Total 
xx ( xx.x%) 
System Organ Class 
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
System Organ Class 
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
 
 
a Counts reflect numbers of subjects reporting one or more TEAEs that map to MedDRA. At each level of summarization (System Organ Class  
 or Preferred Term) subjects are counted once. 
Note: TEAEs are AEs with an onset date after first dose of study drug. 
 
MedDRA Version 21.1.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 


 
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Table 14.3.1.1.3.1: Summary of Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation of Study Drug 
(Safety Population) 
(Page 1 of xx) 
 
System Organ Classa 
Preferred Term 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Total 
xx ( xx.x%) 
System Organ Class 
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
System Organ Class 
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
 
 
a Counts reflect numbers of subjects reporting one or more TEAEs that map to MedDRA. At each level of summarization (System Organ Class  
 or Preferred Term) subjects are counted once. 
Note: TEAEs are AEs with an onset date after first dose of study drug. 
 
MedDRA Version 21.1.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
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Table 14.3.1.1.4.1: Summary of Subjects Reporting Treatment-Emergent Adverse Events (TEAEs) by Severity 
(Safety Population) 
(Page 1 of xx) 
 
System Organ Classa 
Preferred Term 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Total 
Grade 5  
xx ( xx.x%) 
Grade 4  
xx ( xx.x%) 
Grade 3 
xx ( xx.x%) 
Grade 2  
xx ( xx.x%) 
Grade 1  
xx ( xx.x%) 
System Organ Class 
Grade 5  
xx ( xx.x%) 
Grade 4  
xx ( xx.x%) 
Grade 3 
xx ( xx.x%) 
Grade 2  
xx ( xx.x%) 
Grade 1  
xx ( xx.x%) 
Preferred Term  
Grade 5  
xx ( xx.x%) 
Grade 4  
xx ( xx.x%) 
Grade 3 
xx ( xx.x%) 
Grade 2  
xx ( xx.x%) 
Grade 1  
xx ( xx.x%) 
 
 
a Counts reflect numbers of subjects reporting one or more TEAEs that map to MedDRA. At each level of summarization (System Organ Class  
 or Preferred Term) subjects are counted once under the greatest reported severity. 
Note: TEAEs are AEs with an onset date after first dose of study drug. 
 
MedDRA Version 21.1.  
 
Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Life Threatening; Grade 5=Death. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 


 
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Table 14.3.1.1.5.1: Summary of Subjects Reporting Treatment-Emergent Adverse Events (TEAEs) by Relationship to Study Drug 
(Safety Population) 
(Page 1 of xx) 
 
System Organ Classa 
Preferred Term 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Total 
Likely Related  
xx ( xx.x%) 
Likely Unrelated  
xx ( xx.x%) 
System Organ Class 
Likely Related  
xx ( xx.x%) 
Likely Unrelated  
xx ( xx.x%) 
Preferred Term  
Likely Related  
xx ( xx.x%) 
Likely Unrelated  
xx ( xx.x%) 
 
 
a Counts reflect numbers of subjects reporting one or more TEAEs that map to MedDRA. At each level of summarization (System Organ Class  
 or Preferred Term) subjects are counted once under the greatest reported relationship. 
Note: TEAEs are AEs with an onset date after first dose of study drug. 
 
MedDRA Version 21.1.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 
 
 


 
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Table 14.3.1.3.1.1: Summary of Subjects Reporting Serious Treatment-Emergent Adverse Events (TEAEs) by  
MedDRA System Organ Class and Preferred Term 
(Safety Population) 
(Page 1 of xx) 
 
System Organ Classa 
Preferred Term 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Total 
xx ( xx.x%) 
System Organ Class 
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
System Organ Class 
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
Preferred Term  
xx ( xx.x%) 
 
 
a Counts reflect numbers of subjects reporting one or more TEAEs that map to MedDRA. At each level of summarization (System Organ Class  
 or Preferred Term) subjects are counted once. 
Note: TEAEs are AEs with an onset date after first dose of study drug. 
 
MedDRA Version 21.1.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 


 
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Table 14.3.1.3.2.1: Summary of Subjects Reporting Serious Treatment-Emergent Adverse Events (TEAEs) by Severity 
(Safety Population) 
(Page 1 of xx) 
 
System Organ Classa 
Preferred Term 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Total 
Grade 5  
xx ( xx.x%) 
Grade 4  
xx ( xx.x%) 
Grade 3 
xx ( xx.x%) 
Grade 2  
xx ( xx.x%) 
Grade 1  
xx ( xx.x%) 
System Organ Class 
Grade 5  
xx ( xx.x%) 
Grade 4  
xx ( xx.x%) 
Grade 3 
xx ( xx.x%) 
Grade 2  
xx ( xx.x%) 
Grade 1  
xx ( xx.x%) 
Preferred Term  
Grade 5  
xx ( xx.x%) 
Grade 4  
xx ( xx.x%) 
Grade 3 
xx ( xx.x%) 
Grade 2  
xx ( xx.x%) 
Grade 1  
xx ( xx.x%) 
 
 
a Counts reflect numbers of subjects reporting one or more TEAEs that map to MedDRA. At each level of summarization (System Organ Class  
 or Preferred Term) subjects are counted once under the greatest reported severity. 
Note: TEAEs are AEs with an onset date after first dose of study drug. 
 
MedDRA Version 21.1.  
 
Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Life Threatening; Grade 5=Death. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 


 
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Protocol Number: MTI-107  
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Table 14.3.1.3.3.1: Summary of Subjects Reporting Serious Treatment-Emergent Adverse Events (TEAEs) by Relationship to Study Drug 
(Safety Population) 
(Page 1 of xx) 
 
System Organ Classa 
Preferred Term 
 
  
Serlopitant 5 mg  
 
(N=xxx)  
 
Total 
Likely Related  
xx ( xx.x%) 
Likely Unrelated  
xx ( xx.x%) 
System Organ Class 
Likely Related  
xx ( xx.x%) 
Likely Unrelated  
xx ( xx.x%) 
Preferred Term  
Likely Related  
xx ( xx.x%) 
Likely Unrelated  
xx ( xx.x%) 
 
 
a Counts reflect numbers of subjects reporting one or more TEAEs that map to MedDRA. At each level of summarization (System Organ Class  
 or Preferred Term) subjects are counted once under the greatest reported relationship. 
Note: TEAEs are AEs with an onset date after first dose of study drug. 
 
MedDRA Version 21.1.  
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 
 
 
 
 


 
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12 May 2020 
10. INDEX OF PLANNED LISTINGS 
Listing 16.2.1.1: Subject Disposition Information.........................................................................29 
Listing 16.2.1.2: Discontinued Subjects ........................................................................................30 
Listing 16.2.2.1: Inclusion/Exclusion Criteria Not Met ................................................................31 
Listing 16.2.3: Analysis Populations .............................................................................................32 
Listing 16.2.4.1: Subject Demographic Information .....................................................................33 
Listing 16.2.4.2.1: Unique Medical History Coded to MedDRA System Organ Classes and 
Preferred Terms .....................................................................................34 
Listing 16.2.4.2.2: Medical History ...............................................................................................35 
Listing 16.2.4.3: Pruritic Disease History ......................................................................................36 
Listing 16.2.4.4.1: Unique Medication Names Coded to WHO DDE ATC Level 2 Terms and 
Preferred Names ....................................................................................37 
Listing 16.2.4.4.2: Concomitant Medications ................................................................................38 
Listing 16.2.4.5: Concomitant Procedures/Therapies ....................................................................39 
Listing 16.2.4.6: Physical Examination .........................................................................................40 
Listing 16.2.5.1: Study Visit Compliance ......................................................................................41 
Listing 16.2.5.2: Study Drug Dispensing and Return ....................................................................42 
Listing 16.2.6.1: Worst Itch Numeric Rating Scale (WI-NRS) .....................................................43 
Listing 16.2.6.2: IGA PN-S Results...............................................................................................44 
Listing 16.2.6.3: Dermatology Life Quality Index (DLQI) ...........................................................45 
Listing 16.2.6.4: Photography ........................................................................................................46 
Listing 16.2.7.1.1: Unique Adverse Events Coded to MedDRA System Organ Classes and 
Preferred Terms .....................................................................................47 
Listing 16.2.7.1.2: Treatment-Emergent Adverse Events ..............................................................48 
Listing 16.2.7.1.3: Serious Adverse Events ...................................................................................49 
Listing 16.2.7.1.4: Subjects Who Permanently Discontinued Study Drug Due to Adverse 
Events ....................................................................................................50 
Listing 16.2.7.2.1: Hospital Anxiety and Depression Scale ..........................................................51 
Listing 16.2.7.2.2: Epworth Sleepiness Scale ................................................................................52 
Listing 16.2.7.3: Menstrual Diary ..................................................................................................53 
Listing 16.2.8.1: Pregnancy Test Results.......................................................................................54 
Listing 16.2.8.2.1: Laboratory Test Results ...................................................................................55 
Listing 16.2.8.2.2: Out of Range Laboratory Results ....................................................................56 


 
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Listing 16.2.8.2.3: Laboratory Information Captured within Case Report Forms ........................57 
Listing 16.2.8.2.4: Common Laboratory Comments Including Reference Ranges for Specific 
Laboratory Tests....................................................................................58 
Listing 16.2.8.3: Electrocardiogram Test Results ..........................................................................59 
Listing 16.2.8.4: Vital Signs ..........................................................................................................60 
 


 
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12 May 2020 
Listing 16.2.1.1: Subject Disposition Information 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                F: Date of First                                       E: Follow-up Discontinuation 
S: Subject         Dose             R: Reason for Treatment               Date (Day)¹                D: Date of Last Contact 
A: Age/Sex      L: Date of Last        Discontinuation                 R: Reason for Follow-up       P: Primary AE Number/Specify 
E: Evaluable       Dose             P: Primary AE Number/Specify          Discontinuation             
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx       F: xxxx-xx-xx       R: xxxxxxxxxx xx xxxxxxxxxxxxxxx   E: xxxx-xx-xx (xx)            D: xxxx-xx-xx           
A: xxxx         L: xxxx-xx-xx       P: xxxxxxxxxx                      R: xxxxxxxxxx xx xxxxxxxxxx   P: xxxxxxxxxxx                
E: xxxxxxxxx                                                                                          
 
S: xxxxxx       F: xxxx-xx-xx       R: xxxxxxxxxx xx xxxxxxxxxxxxxxx   E: xxxx-xx-xx (xx)            D: xxxx-xx-xx           
A: xxxx         L: xxxx-xx-xx       P: xxxxxxxxxx                      R: xxxxxxxxxx xx xxxxxxxxxx   P: xxxxxxxxxxx                
E: xxxxxxxxx                                                                                          
 
S: xxxxxx       F: xxxx-xx-xx       R: xxxxxxxxx xxxx xxxxxxxx xxxxx   E: xxxx-xx-xx (xx)            D:                            
A: xxxx         L: xxxx-xx-xx       P: xxxxxxxxxx                      R: xxxx xx xxxxxxxxx          P: xxxxxxxxxxx                
E: xxxxxxxxx                                                                                          
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject. 
  
 


 
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12 May 2020 
Listing 16.2.1.2: Discontinued Subjects 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                F: Date of First                                       E: Follow-up Discontinuation 
S: Subject         Dose             R: Reason for Treatment               Date (Day)¹                D: Date of Last Contact 
A: Age/Sex      L: Date of Last        Discontinuation                 R: Reason for Follow-up       P: Primary AE Number/Specify 
E: Evaluable       Dose             P: Primary AE Number/Specify          Discontinuation             
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx       F: xxxx-xx-xx       R: xxxxxxxxxx xx xxxxxxxxxxxxxxx   E: xxxx-xx-xx (xx)            D: xxxx-xx-xx           
A: xxxx         L: xxxx-xx-xx       P: xxxxxxxxxx                      R: xxxxxxxxxx xx xxxxxxxxxx   P: xxxxxxxxxxx                
E: xxxxxxxxx                                                                                          
 
S: xxxxxx       F: xxxx-xx-xx       R: xxxxxxxxxx xx xxxxxxxxxxxxxxx   E: xxxx-xx-xx (xx)            D: xxxx-xx-xx           
A: xxxx         L: xxxx-xx-xx       P: xxxxxxxxxx                      R: xxxxxxxxxx xx xxxxxxxxxx   P: xxxxxxxxxxx                
E: xxxxxxxxx                                                                                          
 
S: xxxxxx       F: xxxx-xx-xx       R: xxxxxxxxx xxxx xxxxxxxx xxxxx   E: xxxx-xx-xx (xx)            D:                            
A: xxxx         L: xxxx-xx-xx       P: xxxxxxxxxx                      R: xxxx xx xxxxxxxxx          P: xxxxxxxxxxx                
E: xxxxxxxxx                                                                                          
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject. 
 
 


 
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12 May 2020 
Listing 16.2.2.1: Inclusion/Exclusion Criteria Not Met 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
Subject     Age/Sex     Evaluable     Criterion Failed    Description 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx      xxxx        xxxxxxxxx     xxxxxx              xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
 
xxxxxx      xxxx        xxxxxxxxx     xxxxx               xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
 
xxxxxx      xxxx        xxxxxxxxx     xxxxx               xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
 
                                      xxxxx               xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
 
                                      xxxxx               xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
                                                          xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxxxxxxxxx xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Criterion Failed. 
 


 
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Listing 16.2.3: Analysis Populations 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
Subject    Age/Sex     Parent Study  Population           Included        Reason(s) Excluded                       
______________________________________________________________________________________________________________________________________ 
xxxxxx     xxxx        xxxx          Safety               xxx 
 
xxxxxx     xxxx        xxxx          Safety               xxx 
 
xxxxxx     xxxx        xxxx          Safety               xxx 
                             
xxxxxx     xxxx        xxxx          Safety               xx              xxxxxxxxxxxxxxx 
                        
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Population (as ordered above). 


 
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Listing 16.2.4.1: Subject Demographic Information 
                                                            (Page xx of yy) 
 _____________________________________________________________________________________________________________________________________ 
 
                                                                                
                    B: Date of Birth                                                                                     
                    A: Age            R: Race                  C: Childbearing Potential    I: Informed Consent Date/Protocol Version    
 Subject  Evaluable S: Sex            E: Ethnicity             M: Method of Contraception   P: Did subject consent to photography?  
 _____________________________________________________________________________________________________________________________________ 
 
 xxxxxx   xxxxxxxxx B: xxxx-xx-xx     R: xxxxxx xxxxxxxx       C: xxx                       I: V2.1/xxxx-xx-xx               
                    A: xx                xx xxxxx xxxxxxx      M: xxxxxxxxx xxxxxxxxxx         V3/xxxx-xx-xx 
                    S: xxxxxx            xxxxxxxx xxxxxxxxxx      xxxxxxxxxxxxx xxxxxxxxx   P: xxx 
                                      E: xxx xxxxxxxx xx          xxxx x xxxxxxxxxx xx  
                                         xxxxxx                   xxxxxxxxx xxxxxxxxxx 
                                                                  xxxx xxxxxxx 
 
 
 xxxxxx   xxxxxxxxx B: xxxx-xx-xx      R: xxxxx                C: xx                        I: V2/xxxx-xx-xx                 
                    A: xx              E: xxxxxxxx xx xxxxxx   M:                           P: xxx       
                    S: xxxx                                                                  
 
 xxxxxx   xxxxxxxxx B: xxxx-xx-xx      R: xxxxx                C: xxx                       I: V3/xxxx-xx-xx                      
                    A: xx              E: xxxxxxxx xx xxxxxx   M: xxxxxxxx xxxxxxxxxxxxx    P: xxx                                 
                    S: xxxxxx            
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 _____________________________________________________________________________________________________________________________________ 
 Note: S = Safety Population. 
 SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject. Include all instances of informed consents and associated protocol versions. 
  
 


 
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12 May 2020 
        Listing 16.2.4.2.1: Unique Medical History Coded to MedDRA System Organ Classes and Preferred Terms 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
MedDRA System Organ Class                     MedDRA Preferred Term                       Medical History Verbatim Term 
______________________________________________________________________________________________________________________________________ 
 
xxxx xxx xxxxx                                xxxx xxx xxxxx                              xxxx 
 
                                                                                          xxxxxx xxxxxxxxxx xx xxxxxx 
 
                                                                                          xxxxxx xxxxxxxxxx xx xxxxx 
 
 
xxxx xxx xxxxx                                xxxx xxx xxxxx                              xxxx 
 
                                                                                          xxxxxx xxxxxxxxxx xx xxxxxx 
 
                                                                                          xxxxxx xxxxxxxxxx xx xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                           
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term map to the MedDRA dictionary (Version 21.1). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by MedDRA System Organ Class, MedDRA Preferred Term, and Medical History Verbatim Term. 
 
 
 
 
 
 


 
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Listing 16.2.4.2.2: Medical History 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
        
                                                                                                       
 
                                                               
 
                                                                     P: MedDRA Preferred Term         
S: Onset Date 
Subject    Age/Sex    Evaluable    M: Medical Condition              S: MedDRA System Organ Class         
E: End Date 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx       xxxxxxxx     M: xxxx xxxxxxx (xxxxxxxx xxxxx)  P: xxxxxx xxxxxxxxxx               
S: xxxx-xx-xx 
                                 
S: xxxxxxxxxxx xxxxxxx             
E:  
 
 
 
 
 
                            
                                                        M: xxxx xxxxxxx (xxxxxxxx xxxxx)  P: xxxxxx xxxxxxxxxx               
S: xxxx-xx-xx 
                        
S: xxxxxxxxxxx xxxxxxx             
E:  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
                    
           
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: S = Safety Population. 
      System Organ Class and Preferred Term map to MedDRA (Version 21.1). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Medical Condition/Surgery Verbatim Term, Onset Date, and End Date. 
 
 


 
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Listing 16.2.4.3: Pruritic Disease History 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
        
                                                                                          
                                                   Date of        Body Locations                     
Subject  Age/Sex  Evaluable  Indication            Diagnosis      Affected                       
______________________________________________________________________________________________________________________________________ 
 
xxxxxx   xxxx     xxxxxxxx   Prurigo Nodularis     xxxx-xx-xx     xxxxxxxxx xxxxx; xxxxxx; xxxx           
                                                                  xxx xxxx; xxxxxxxxx              
   
xxxxxx   xxxx     xxxxxxxx   Atopic Dermatitis     xxxx-xx-xx     xxxxxxxxx xxxxx; xxxxx xxxxx;           
                                                                  xxxxx; xxxxxxxxx                 
                                                                               
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject. 
 
 
 
 
 
 
 
 
 


 
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Listing 16.2.4.4.1: Unique Medication Names Coded to WHO DDE ATC Level 2 Terms and Preferred Names 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                                                                                                             I: Indication 
ATC Level 2 Term                 Standardized Medication Name           Medication Name                      R: Route 
______________________________________________________________________________________________________________________________________ 
 
xxxxxxxxxxxxxx                   xxxxxxxxxxxxxx                         xxxxxxxx                             I: xxxxxxxxxxx 
                                                                                                             R: xxxxxxxxxxx 
 
                                                                        xxxxxxxxx                            I: xxxxxxxxxxx 
                                                                                                             R: xxxxxxxxxxx 
 
 
xxxxxxxxxxxxxx                   xxxxxxxxxxxxxx                         xxxxxxxx                             I: xxxxxxxxxxx 
                                                                                                             R: xxxxxxxxxxx 
 
                                                                        xxxxxxxxx                            I: xxxxxxxxxxx 
                                                                                                             R: xxxxxxxxxxx 
                                                                                                               
 
             
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                             
______________________________________________________________________________________________________________________________________ 
Note: Standardized Medication Name and ATC Level 2 Term map to the WHO DDE (Version September 1, 2018). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by ATC Level 2 Term, Standardized Medication Name, Medication Name, Indication, and Route. 
 
Note to Programmer: If Indication or Route is ‘Other’ then the applicable variable is ‘OTHER: <specification of other>’.  
 
 


 
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Listing 16.2.4.4.2: Concomitant Medications 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                                      M: Medication Name                      T: Prior/Concomitant            D: Dose 
                                      P: Standardized Medication Name         F: Date of First Dose           U: Units 
                                      A: ATC Level 2 Term                     S: Start Date (Day)¹            F: Frequency 
Subject     Age/Sex    Evaluable      I: Indication                           E: End Date (Day)¹              R: Route  
______________________________________________________________________________________________________________________________________ 
 
xxxxxx      xxxx       xxxxxxxxxx     M: xxxxxxxxxxxxx                        T: xxxxxxxxxx                    D: xx 
                                      P: xxxxxxxxxxxxx                        F: xxxx-xx-xx                    U: xx 
                                      A: xxxxxxxxxxxxx                        S: xxxx-xx-xx (xx)               F: xxxx 
                                      I: xxxxxxxx                             E: xxxx-xx-xx (xx)               R: xxxxxx  
                                                                                                               
 
                                      M: xxxxxxxxxxxxx                        T: xxxxxxxxxx                    D: xxxxx 
                                      P: xxxxxxxxxxxxx                        F: xxxx-xx-xx                    U: xx 
                                      A: xxxxxxxxxxxxx                        S: xxxx-xx                       F: xx 
                                      I: xxxxxxxx                             E:                               R: xxxx 
                                                                                                               
 
xxxxxx      xxxx       xxxxxxxxxx     M: xxxxxxxxxxxxx                        T: xxxxxxxxxx                    D: xxx 
                                      P: xxxxxxxxxxxxx                        F: xxxx-xx-xx                    U: xx 
                                      A: xxxxxxxxxxxxx                        S: xxxx-xx-xx (x)                F: xx 
                                      I: xxxxxxxx                             E: xxxx-xx-xx (xx)               R: xxxx 
                                                                                                             
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
      Standardized Medication Name and ATC Level 2 Term map to the WHO DDE (Version September 1, 2018). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
Listing sorted by Subject, Start Date, End Date, Medication Name, Indication, and Route. If ongoing, include ‘Ongoing’ in place of End 
Date. 
Note to Programmer: If Units, Frequency, Indication, or Route is ‘Other’ then the applicable variable is ‘OTHER: <specification of 
other>’. 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
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Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.4.5: Concomitant Procedures/Therapies 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                                                                         F: Date of First Dose 
                                                                         S: Start Date (Day)¹        Reason for Procedure 
Subject    Age/Sex    Evaluable     Procedure/Therapy                    E: End Date (Day)¹          or Therapies 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx      xxxx      xxxxxxxxxx    xxxxxxxxxxxxx                        F: xxxx-xx-xx               x xxxxxx xxxx xxxxxx  
                                                                         S: xxxx-xx-xx (xx)          xxxxxxxxx 
                                                                         E: xxxx-xx-xx (xx)                               
                                                                                                               
xxxxxx      xxxx      xxxxxxxxxx    xxxxxxxxxxxxx                        F: xxxx-xx-xx               x xxxxxx xxxx xxxxxx  
                                                                         S: xxxx-xx                  xxxxxxxxx 
                                                                         E: xxxx-xx-xx (xx)                              
                                                                                                               
xxxxxx      xxxx      xxxxxxxxxx    xxxxxxxxxxxxx                        F: xxxx-xx-xx               x xxxxxx xxxx xxxxxx  
                                                                         S: xxxx-xx-xx (xx)          xxxxxxxxx 
                                                                         E: xxxx-xx-xx (xx)                               
 
                                                                         F: xxxx-xx-xx               x xxxxxx xxxx xxxxxx  
                                                                         S: xxxx-xx-xx (xx)          xxxxxxxxx 
                                                                         E: xxxx-xx-xx (xx)                                                            
                                                                                                             
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, and Procedure/Therapy. If ongoing, include ‘Ongoing’ in place of End Date. 
 
 


 
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Listing 16.2.4.6: Physical Examination 
                                                            (Page x of xx) 
 _____________________________________________________________________________________________________________________________________ 
 
 Subject        Age/Sex     Evaluable   Visit           Date of Assessment (Day)¹   Physical Exam Completed      
 _____________________________________________________________________________________________________________________________________ 
 
 xxxxxxxxxx     xxxx        xxxxxxxxx   xxxxxxxxxx      xxxx-xx-xx (xx)             xxxxxxxx                                                    
 
 xxxxxxxxxx     xxxx        xxxxxxxxx   xxxxxxxxxx      xxxx-xx-xx (xx)             xxxxxxxx                                               
 
 xxxxxxxxxx     xxxx        xxxxxxxxx   xxxxxxxxxx      xxxx-xx-xx (xx)             xxxxxxxx                                               
 
 xxxxxxxxxx     xxxx        xxxxxxxxx   xxxxxxxxxx      xxxx-xx-xx (x)              xxxxxxxx                                               
 
 xxxxxxxxxx     xxxx        xxxxxxxxx   xxxxxxxxxx      xxxx-xx-xx (xx)             xxxxxxx                                                        
                                                                                                                                                       
 
 xxxxxxxxxx     xxxx        xxxxxxxxx   xxxxxxxxxx      xxxx-xx-xx (xx)             xxxxxxxx                                                   
 
 
 
 
 
 
 
 
 
 
 
_____________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, and Date of Assessment. 
 
                                                
 
 
 
 


 
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Protocol Number: MTI-107  
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Listing 16.2.5.1: Study Visit Compliance 
                                                           (Page xx of yy) 
_____________________________________________________________________________________________________________________________________ 
 
                                                                                                               
                                                                  Visit Not Done/  
Subject  Age/Sex  Evaluable Visit                Visit Date       Reason for Unscheduled Visit 
_____________________________________________________________________________________________________________________________________ 
 
xxxxxx    xxxx    xxxxxxxx  xxxxxxxxx            xxxx-xx-xx      
 
                            xxxxxxxx             xxxx-xx-xx      
 
                            xxxxxx               xxxx-xx-xx      
 
                            xxxxxx               xxxx-xx-xx       x xxxx xxxxxxx x xxxxxx xxxxxxx xxxxx xxxxxx 
                                                                  xx xxxx xxx xxxx xx xxx xxxx 
 
                            xxxxxx               xxxx-xx-xx      
 
                            xxxxxxxxxxxxxxx      xxxx-xx-xx      
 
 
xxxxxx    xxxx    xxxxxxxx  xxxxxxxxx            xxxx-xx-xx      
 
                            xxxxxx               xxxx-xx-xx      
 
                            xxxxxxxxxxxxxxx      xxxx-xx-xx      
 
 
 
 
_____________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – baseline date for dates prior to baseline date. Otherwise, day is calculated as 
  date – baseline date + 1 for dates on or after baseline date. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME)  
 
Listing sorted by Subject, Visit, and Visit Date. 
 
Note to Programmer: If a visit is ranged present the ‘Visit Date’ column as ‘<Start Date> to <End Date>’ same with the Study Day 
column. 
 
 
 


 
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Listing 16.2.5.2: Study Drug Dispensing and Return 
                                                            (Page xx of yy) 
 _____________________________________________________________________________________________________________________________________  
                                    
                                              
                                   Bottle     Date Bottle  Date Bottle    Number of Tablets    Number of Tablets                      
 Subject   Age/Sex    Evaluable    Number     Dispensed    Returned           Dispensed            Returned            Tablets Used 
 _____________________________________________________________________________________________________________________________________ 
 
 xxxxxx    xxxx       xxxxxxxxx    xxxxxx     xxxx-xx-xx   xxxx-xx-xx             xx                   xx                   xx               
                                   xxxxxx     xxxx-xx-xx   xxxx-xx-xx             xx                   xx                   xx               
 
 xxxxxx    xxxx       xxxxxxxxx    xxxxxx     xxxx-xx-xx   xxxx-xx-xx             xx                   xx                   xx               
                                   xxxxxx     xxxx-xx-xx   xxxx-xx-xx             xx                   xx                   xx               
 
         
 
  
 
 
 
 
 
 
 
 _____________________________________________________________________________________________________________________________________ 
 Note: S = Safety Population. 
 SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Date Bottle Dispensed, and Date Bottle Returned. 
 
 
 
 
 
 
 
 
 
 
 


 
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Listing 16.2.6.1: Worst Itch Numeric Rating Scale (WI-NRS) 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
Subject      Age/Sex   Evaluable   Visit                      Date of Assessment (Day)¹          WI-NRS² in the past 24 hours 
______________________________________________________________________________________________________________________________________ 
   
xxxxxxxx     xxxx      xxxxxxxxx   xxxxxxxxxxxxxxxxxxxxx      xxxx-xx-xx (xx)                    xx 
 
xxxxxxxx     xxxx      xxxxxxxxx   xxxxxxxxxxxxxxxxxxxxx      xxxx-xx-xx (xx)                    xx 
 
xxxxxxxx     xxxx      xxxxxxxxx   xxxxxxxxxxxxxxxxxxxxx      xxxx-xx-xx (xx)                    xx 
 
xxxxxxxx     xxxx      xxxxxxxxx   xxxxxxxxxxxxxxxxxxxxx      xxxx-xx-xx (xx)                    xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
² Scaled from 0 - No Itch to 10 - Worst Itch Imaginable. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Date of Assessment. 
 
 
 
 
 
 
 


 
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Listing 16.2.6.2: IGA PN-S Results 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                                                                             Investigator’s Global Assessement  
Subject   Age/Sex  Evaluable   Visit              Date of Assessment (Day)¹  of Prurigo Nodularis Stage         
______________________________________________________________________________________________________________________________________ 
     
xxxxxxxx  xxxx     xxxxxxxxx   xxxxxxxxxxxxx      xxxx-xx-xx (xx)                         xxxxx x               
                               xxxxxxxxxxxxx      xxxx-xx-xx (xx)                         xxxxx x               
                               xxxxxxxxxxxxx      xxxx-xx-xx (xx)                         xxxxx x                  
                               xxxxxxxxxxxxx      xxxx-xx-xx (xx)                         xxxxx x                  
                               xxxxxxxxxxxxx      xxxx-xx-xx (xx)                         xxxxx x                  
                               xxxxxxxxxxxxx      xxxx-xx-xx (xx)                         xxxxx x               
   
xxxxxxxx  xxxx     xxxxxxxxx   xxxxxxxxxxxxx      xxxx-xx-xx (xx)                         xxxxx x               
                               xxxxxxxxxxxxx      xxxx-xx-xx (xx)                         xxxxx x               
                               xxxxxxxxxxxxx      xxxx-xx-xx (xx)                         xxxxx x                  
                               xxxxxxxxxxxxx      xxxx-xx-xx (xx)                         xxxxx x                  
                               xxxxxxxxxxxxx      xxxx-xx-xx (xx)                         xxxxx x                  
                               xxxxxxxxxxxxx      xxxx-xx-xx (xx)                         xxxxx x               
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, and Date of Assessment. 
 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 45 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.6.3: Dermatology Life Quality Index (DLQI) 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                           V: Visit                      Question 
Subject  Age/Sex Evaluable D: Date of Assessment (Day)¹   Number  Question                                                Result 
______________________________________________________________________________________________________________________________________ 
 
xxxxxxxx xxxx    xxxxxxx   V: xxxxxxxxxx                     1    Over the last week, how itchy, sore, painful or         xxxxxx 
                           D: xxxx-xx-xx (xx)                     stinging has your skin been? 
                                                             2    Over the last week, how embarrassed or self conscious   xxxxxx 
                                                                  have you been because of your skin? 
                                                             3    Over the last week, how much has your skin interfered   xxxxxx 
                                                                  with you going shopping or looking after your home or 
                                                                  garden? 
                                                             4    Over the last week, how much has your skin influenced   xxxxxx 
                                                                  the clothes you wear? 
                                                             5    Over the last week, how much has your skin affected     xxxxxx 
                                                                  any social or leisure activities? 
                                                             6    Over the last week, how much has your skin made it      xxxxxx 
                                                                  difficult for you to do any sport? 
                                                             7    Over the last week, has your skin prevented you from    xxxxxx 
                                                                  working or studying? 
                                                            7A    If "No", over the last week how much has your skin      xxxxxx 
                                                                  been a problem at work or studying? 
                                                             8    Over the last week, how much has your skin created      xxxxxx 
                                                                  problems with your partner or any of your close 
                                                                  friends or relatives? 
                                                             9    Over the last week, how much has your skin caused any   xxxxxx 
                                                                  sexual difficulties? 
                                                            10    Over the last week, how much of a problem has the       xxxxxx 
                                                                  treatment for your skin been, for example by making 
                                                                  your home messy, or by taking up time? 
                                                                  Questionnaire Score                                     xx 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, and Date of Assessment. 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 46 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.6.4: Photography 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                           V: Visit                       
Subject  Age/Sex Evaluable D: Date of Assessment (Day)¹  Body Areas Photographed 
______________________________________________________________________________________________________________________________________ 
 
xxxxxxxx xxxx    xxxxxxx   V: xxxxxxxxxx                 xxxxxxxx; xxxxxxxxxxx; xxxxxxxx 
                           D: xxxx-xx-xx (xx)             
                                                          
                                                          
                           V: xxxxxxxxxx                 xxxxxxxx; xxxxxxxxxxx; xxxxxxxx 
                           D: xxxx-xx-xx (xx)             
                                 
                                 
                           V: xxxxxxxxxx                 xxxxxxxx; xxxxxxxxxxx; xxxxxxxx 
                           D: xxxx-xx-xx (xx)             
                                 
                                 
                           V: xxxxxxxxxx                 xxxxxxxx; xxxxxxxxxxx; xxxxxxxx 
                           D: xxxx-xx-xx (xx)             
                                                          
                                                          
                                                          
                                                          
                                                          
                                                          
                                                          
                                                          
                                                          
                                                          
                                                          
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, and Date of Assessment. 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 47 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.7.1.1: Unique Adverse Events Coded to MedDRA System Organ Classes and Preferred Terms 
                                                             (Page xx of yy) 
 _____________________________________________________________________________________________________________________________________ 
 
 MedDRA System Organ Class                    MedDRA Preferred Term                        Adverse Event 
 _____________________________________________________________________________________________________________________________________ 
 
 xxxxx xxxxx xxxxx                            xxxxx xxxxx xxxxx                            xxxxxxxxxx 
 
                                                                                           xxxxxxxx xxxxxxxx xxxxxxxxxxx 
 
                                                                                           xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx 
 
 
                                              xxxxx xxxxx xxxxx                            xxxxxxxxxx 
 
                                                                                           xxxxxxxx xxxxxxxx xxxxxxxxxxx 
 
                                                                                           xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx 
 
                                                                                            
                                              xxxxxxxxxx                                   xxxxx xxxxx xxxxx                             
 
                                                                                           xxxxxxxx xxxxxxxx xxxxxxxxxxx 
 
                                                                                           xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 _____________________________________________________________________________________________________________________________________ 
 Note: System Organ Class and Preferred Term map to MedDRA (Version 21.1). 
 SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by MedDRA System Organ Class, Preferred Term, and Adverse Event. 
 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 48 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.7.1.2: Treatment-Emergent Adverse Events 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                                                                                                     S: Is AE Serious? 
                                                                         S: Grade²                   R: Reason(s) for Serious 
S: Subject         A: Event                   F: Date of First Dose      R: Relationship to Study    T: Action Taken with 
A: Age/Sex         C: System Organ Class      S: Start Date (Day)¹          Treatment                   Study Treatment 
E: Evaluable       P: Preferred Term          E: End Date (Day)¹         O: Outcome                  A: Any Other Action(s) 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx          A: xxxxxxxxxxxxxxx         F: xxxx-xx-xx              S: xxxx                     S: xx 
A: xxxx            C: xxxxxxxxxxxxxxx         S: xxxx-xx-xx (xx)         R: xxxxxxxxxx               R: xxxx xxx xxxxxxx 
E: xxxxxxxxx       P: xxxxxxxxxxxxxxx         E: xxxx-xx-xx (xx)         O: xxxxxxxxxx               T: xxx 
                                                                                                     A: xxxxxxx 
 
                   A: xxxxxxxxxxxxxxx         F: xxxx-xx-xx              S: xxxx                     S: xx 
                   C: xxxxxxxxxxxxxxx         S: xxxx-xx-xx (x)          R: xxxxxxxxxx               R: xxxx xxx xxxxxxx 
                   P: xxxxxxxxxxxxxxx         E: xxxx-xx-xx (xx)         O: xxxxxxxxxx               T: xxx 
                                                                                                     A: xxxxxxx 
 
S: xxxxxx          A: xxxxxxxxxxxxxxx         F: xxxx-xx-xx              S: xxxx                     S: xx 
A: xxxx            C: xxxxxxxxxxxxxxx         S: xxxx-xx-xx (xx)         R: xxxxxxxxxx               R: xxxx xxx xxxxxxx 
E: xxxxxxxxx       P: xxxxxxxxxxxxxxx         E: xxxx-xx-xx (xx)         O: xxxxxxxxxx               T: xxx 
                                                                                                     A: xxxxxxx 
S: xxxxxx          A: xxxxxxxxxxxxxxx         F: xxxx-xx-xx              S: xxxx                     S: xx 
A: xxxx            C: xxxxxxxxxxxxxxx         S: xxxx-xx-xx (xx)         R: xxxxxxxxxx               R: xxxx xxx xxxxxxx 
E: xxxxxxxxx       P: xxxxxxxxxxxxxxx         E: xxxx-xx-xx (xx)         O: xxxxxxxxxx               T: xxx 
                                                                                                     A: xxxxxxx 
 
 
 
 
 
 
  
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
2 Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life Threatening; Grade 5 = Death. 
Note: S = Safety Population. 
      System Organ Class and Preferred Term map to MedDRA (Version 21.1). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, and Adverse Event. 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 49 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.7.1.3: Serious Adverse Events 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
                                                                                    
                                                                                                     S: Is AE Serious? 
                                                                         S: Grade2                    R: Reason(s) for Serious    
S: Subject         A: Event                   F: Date of First Dose      R: Relationship to Study    T: Action Taken with     
A: Age/Sex         C: System Organ Class      S: Start Date (Day)¹          Treatment                   Study Treatment 
E: Evaluable       P: Preferred Term          E: End Date (Day)1          O: Outcome                  A: Any Other Action(s)  
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx          A: xxxxxxxxxxxxxxx         F: xxxx-xx-xx              S: xxxx                     S: xx 
A: xxxx            C: xxxxxxxxxxxxxxx         S: xxxx-xx-xx (xx)         R: xxxxxxxxxx               R: xxxx xxx xxxxxxx 
E: xxxxxxxxx       P: xxxxxxxxxxxxxxx         E: xxxx-xx-xx (xx)         O: xxxxxxxxxx               T: xxx 
                                                                                                     A: xxxxxxx 
 
                   A: xxxxxxxxxxxxxxx         F: xxxx-xx-xx              S: xxxx                     S: xx 
                   C: xxxxxxxxxxxxxxx         S: xxxx-xx-xx (x)          R: xxxxxxxxxx               R: xxxx xxx xxxxxxx 
                   P: xxxxxxxxxxxxxxx         E: xxxx-xx-xx (xx)         O: xxxxxxxxxx               T: xxx 
                                                                                                     A: xxxxxxx 
 
S: xxxxxx          A: xxxxxxxxxxxxxxx         F: xxxx-xx-xx              S: xxxx                     S: xx 
A: xxxx            C: xxxxxxxxxxxxxxx         S: xxxx-xx-xx (xx)         R: xxxxxxxxxx               R: xxxx xxx xxxxxxx 
E: xxxxxxxxx       P: xxxxxxxxxxxxxxx         E: xxxx-xx-xx (xx)         O: xxxxxxxxxx               T: xxx 
                                                                                                     A: xxxxxxx 
S: xxxxxx          A: xxxxxxxxxxxxxxx         F: xxxx-xx-xx              S: xxxx                     S: xx 
A: xxxx            C: xxxxxxxxxxxxxxx         S: xxxx-xx-xx (xx)         R: xxxxxxxxxx               R: xxxx xxx xxxxxxx 
E: xxxxxxxxx       P: xxxxxxxxxxxxxxx         E: xxxx-xx-xx (xx)         O: xxxxxxxxxx               T: xxx 
                                                                                                     A: xxxxxxx 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
2 Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life Threatening; Grade 5 = Death. 
Note: S = Safety Population. 
      System Organ Class and Preferred Term map to MedDRA (Version 21.1). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, and Adverse Event. 
 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 50 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.7.1.4: Subjects Who Permanently Discontinued Study Drug Due to Adverse Events 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                                      _______Completion/Discontinuation________ 
                                      D: Date of Study Discontinuation (Day)¹   ____________________Adverse Events____________________ 
                   F: Date of First   T: Primary Reason for Treatment           A: Event                   S: Start Date (Day)¹ 
S: Subject            Dose               Discontinuation                        S: Grade²                  E: End Date (Day)¹ 
A: Age/Sex         L: Date of Last    S: Primary Reason for Study               R: Relationship to         A: Action Taken with Study 
E: Evaluable          Dose               Discontinuation                           Study Treatment            Treatment 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx          F: xxxx-xx-xx      D: xxxx-xx-xx (xx)                        A: xxxxxxxxxx              S: xxxx-xx-xx (xx) 
A: xxxx            L: xxxx-xx-xx      T: xxxxxx                                 S: xxxxxxx                 E: xxxx-xx-xx (xx) 
E: xxxxxxx                            S: xxxxxxxxxxxxxx                         R: xxxxxxxxxxxxxxxx        A: xxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
² Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life Threatening; Grade 5 = Death. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, and Adverse Event. 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 51 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.7.2.1: Hospital Anxiety and Depression Scale 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                           V: Visit                       
Subject  Age/Sex Evaluable D: Date of Assessment (Day)¹  Question                                             Result 
______________________________________________________________________________________________________________________________________ 
 
xxxxxxxx xxxx    xxxxxxx   V: xxxxxxxxxx                 I feel tense or ‘wound up’                           xxxxxxxxxxxxxxxxxxxx 
                           D: xxxx-xx-xx (xx)            I still enjoy the things I used to enjoy             xxxxxxxxxxxxxxxxxxxx 
                                                         I get a sort of frightened feeling as if something 
                                                         awful is about to happen                             xxxxxxxxxxxxxxxxxxxx 
                                                         I can laugh and see the funny side of things         xxxxxxxxxxxxxxxxxxxx 
                                                         Worrying thoughts go through my mind                 xxxxxxxxxxxxxxxxxxxx 
                                                         I feel cheerful                                      xxxxxxxxxxxxxxxxxxxx 
                                                         I can sit at ease and feel relaxed                   xxxxxxxxxxxxxxxxxxxx 
                                                         Depression Subscale                                  xx 
                                                         Anxiety Subscale                                     xx 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 52 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.7.2.2: Epworth Sleepiness Scale 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                           V: Visit                       
Subject  Age/Sex Evaluable D: Date of Assessment (Day)¹  Situation                                                Result 
______________________________________________________________________________________________________________________________________ 
 
xxxxxxxx xxxx    xxxxxxx   V: xxxxxxxxxx                 Sitting and reading                                      xxxxxxxxxxxxxxxxxxxx 
                           D: xxxx-xx-xx (xx)            Watching TV                                              xxxxxxxxxxxxxxxxxxxx 
                                                         Sitting, inactive in a public place (e.g. a theatre  
                                                         or a meeting)                                            xxxxxxxxxxxxxxxxxxxx 
                                                         As a passenger in a car for an hour without a break      xxxxxxxxxxxxxxxxxxxx 
                                                         Lying down to rest in the afternoon when circumstances  
                                                         permit                                                   xxxxxxxxxxxxxxxxxxxx 
                                                         Sitting and talking to someone                           xxxxxxxxxxxxxxxxxxxx 
                                                         Sitting quietly after a lunch without alcohol            xxxxxxxxxxxxxxxxxxxx 
                                                         In a car, while stopped for a few minutes in the  
                                                         traffic                                                  xxxxxxxxxxxxxxxxxxxx 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 53 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.7.3: Menstrual Diary 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                            
Subject  Age/Sex Evaluable    Childbearing Potential      Start Date of Period (Day)¹       End Date of Period (Day)¹ 
______________________________________________________________________________________________________________________________________ 
 
xxxxxxxx xxxx    xxxxxxx      xxxxxxxxxxxxx               xxxx-xx-xx (xx)                   xxxx-xx-xx (xx) 
                                                          xxxx-xx-xx (xx)                   xxxx-xx-xx (xx) 
                                                          xxxx-xx-xx (xx)                   xxxx-xx-xx (xx) 
                            
                            
                            
                            
                            
                            
                            
                            
                            
                            
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 54 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.8.1: Pregnancy Test Results 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
                                                                                S: Was a Serum Pregnancy 
S: Subject                                                                         Test Ordered? 
A: Age/Sex        V: Visit                       S: Specimen²                   E: If no, but was required, 
E: Evaluable      D: Date (Day)¹                 R: Result                         explain                            Comments 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx         V: xxxxxxxxx                   S: xxxxx                       S: xxx                                xxxxxxxxxxxxxx 
A: xxxx           D: xxxx-xx-xx (xxx)            R: xxxxxxxx                    E: 
E: xxxxxxxx 
                                                     
                  V: xxxxxxxxx                   S: xxxxx                       S: xx 
                  D: xxxx-xx-xx (xxx)            R: xxxxxxxx                    E: 
 
                  V: xxxxxxxxx                   S: xxxxx                       S: xx 
                  D: xxxx-xx-xx (xxx)            R: xxxxxxxx                    E: 
 
                  V: xxxxxxxxx                   S: xxxxx                       S: xx 
                  D: xxxx-xx-xx (xxx)            R: xxxxxxxx                    E: 
 
S: xxxxxx         V: xxxxxxxxx                   S: xxxxx                       S: xx 
A: xxxx           D: xxxx-xx-xx (xxx)            R: xxxxxxxx                    E: xxxxxxxxxxxxxxxxxxxxxxxxxx 
E: xxxxxxxx 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
² For Serum pregnancy results: HCG levels less than 10 mIU/mL are considered negative for pregnancy. Levels between 10 - 24.9 mIU/mL 
  are equivocal and a redraw of the patient after 48 hours is suggested. Levels greater than or equal to 25 mUI/mL are considered 
  positive for pregnancy. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, Date, and Specimen.  NOTE: Serum Pregnancy Questions (S: E:) are only applicable to Urine Pregnancy 
test records. 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 55 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.8.2.1: Laboratory Test Results 
                                                           (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
S: Subject   V: Visit 
A: Age/Sex   D: Date (Day)¹                                       Results       _______Reference Range________ 
E: Evaluable C: Category                   Laboratory Test        (Units)       Low   High  Indicator          Comments 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx    V: xxxxxxxxx                  xxxxxxxxxxxxxxxxxxxxxx xxxx (xxxxxx)                                xxxxxxxxxxxxxxxxxxxx 
A: xxxx      D: xxxx-xx-xxTxx:xx:xx (xxx)                                                                      xxxxxxxxxxxxxxxxxx 
E: xxxxxxxx  C: xxxxxxxxxxxxxxxxxxxxxx                                                                         xxxxxxxxxxxxxx 
 
             V: xxxxxxxxx                  xxxxxxxxxxxxxxxxxxxxxx xxxx (xxxxxx) x     xx    xxxxxxxxxxx (xxx)  xxxxxxxxxxxxxxx 
             D: xxxx-xx-xxTxx:xx:xx (xxx)                                                                      xxxxxxxxxxxxxxxxxx 
             C: xxxxxxxxxxxxxxxxxxxxxx                                                                         xxxxxxxxxxxxxx 
 
             V: xxxxxxxxx                  xxxxxxxxxxxxxxxxxxxxxx xxxx (xxxxxx) x     xx    xxxxxxxxxxx (xxx)   
             D: xxxx-xx-xxTxx:xx:xx (xxx)                                                                       
             C: xxxxxxxxxxxxxxxxxxxxxx                                                                          
 
                                                                         
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, Date, Category, and Lab Test.  
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 56 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.8.2.2: Out of Range Laboratory Results 
                                                            (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
S: Subject   V: Visit 
A: Age/Sex   D: Date (Day)¹                                       Results       _______Reference Range________ 
E: Evaluable C: Category                   Laboratory Test        (Units)       Low   High  Indicator(CS²)     Comments 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx    V: xxxxxxxxx                  xxxxxxxxxxxxxxxxxxxxxx xxxx (xxxxxx)                                xxxxxxxxxxxxxxxxxxxx 
A: xxxx      D: xxxx-xx-xxTxx:xx:xx (xxx)                                                                      xxxxxxxxxxxxxxxxxx 
E: xxxxxxxx  C: xxxxxxxxxxxxxxxxxxxxxx                                                                         xxxxxxxxxxxxxx 
 
             V: xxxxxxxxx                  xxxxxxxxxxxxxxxxxxxxxx xxxx (xxxxxx) x     xx    xxxxxxxxxxx (xxx)  xxxxxxxxxxxxxxx 
             D: xxxx-xx-xxTxx:xx:xx (xxx)                                                                      xxxxxxxxxxxxxxxxxx 
             C: xxxxxxxxxxxxxxxxxxxxxx                                                                         xxxxxxxxxxxxxx 
 
             V: xxxxxxxxx                  xxxxxxxxxxxxxxxxxxxxxx xxxx (xxxxxx) x     xx    xxxxxxxxxxx (xxx)   
             D: xxxx-xx-xxTxx:xx:xx (xxx)                                                                       
             C: xxxxxxxxxxxxxxxxxxxxxx                                                                          
 
                                                                         
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
² Clinical significance based on Investigator interpretation. CS = Clinically Significant; NCS = Not Clinically Significant. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, Date, Category, and Lab Test. 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 57 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.8.2.3: Laboratory Information Captured within Case Report Forms 
                                                           (Page xx of yy) 
______________________________________________________________________________________________________________________________________ 
 
S: Subject    
A: Age/Sex   V: Visit                      Y: Was sample collected?          
E: Evaluable C: Category                   D: Date of Sample Collection     Were there any abnormal results? 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx    V: xxxxxxxxx                  Y: xxx 
A: xxxx      C: xxxxxxxxxxxxxxxxxxxxxx     D: xxxx-xx-xx                    xxxxxxxxxxxxxx 
E: xxxxxxxx   
 
S: xxxxxx    V: xxxxxxxxx                  Y: xxx 
A: xxxx      C: xxxxxxxxxxxxxxxxxxxxxx     D: xxxx-xx-xx                    xxxxxxxxxxxxxx 
E: xxxxxxxx   
 
                                                                         
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, Date, Category, and Lab Test.  
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 58 
Protocol Number: MTI-107  
12 May 2020 
               Listing 16.2.8.2.4: Common Laboratory Comments Including Reference Ranges for Specific Laboratory Tests 
                                                            (Page 1 of 1) 
______________________________________________________________________________________________________________________________________ 
 
Category               Laboratory Test        Comments 
______________________________________________________________________________________________________________________________________ 
 
xxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
                       xxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
xxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
xxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
                                              xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Category and Lab Test. 
 
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 59 
Protocol Number: MTI-107  
12 May 2020 
 
Listing 16.2.8.3: Electrocardiogram Test Results 
                                                            (Page x of xx) 
_____________________________________________________________________________________________________________________________________ 
 
S: Subject 
A: Age/Sex                                   V: Visit                                                Clinical 
E: Evaluable    Category    ECG Parameter    D: Date/Time of ECG (Day)¹      Result (unit)         Significance2   Comments      
_____________________________________________________________________________________________________________________________________ 
 
S: xxxxxxxxx    xxxxxxxxxx xxxxxxxxxx        V: xxxxxxxxx                    xxxx xxxxx xx (xxx)       xxx 
A: xxxx                                      D: xxxx-xx-xxTxx:xx:xx (xx) 
E: xxx/xx/xxx    
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
2  Clinical significance based on Investigator interpretation. CS = Clinically Significant; NCS = Not Clinically Significant. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Category, Parameter, Visit, and Date. Note: for interpretation records, EGEVAL should be concatenated into 
ECG Parameter as EGTEST (EGEVAL). 
 
Include information captured within CRF as a separate parameter within listing.  
 


 
Statistical Analysis Plan for Menlo Therapeutics Inc. 
Page 60 
Protocol Number: MTI-107  
12 May 2020 
Listing 16.2.8.4: Vital Signs 
                                                            (Page x of xx) 
______________________________________________________________________________________________________________________________________ 
 
Subject    Age/Sex    Evaluable    Visit          Date of Measurements (Day)¹     Vital Sign                Result       Units 
______________________________________________________________________________________________________________________________________ 
 
xxxxxxxxx  xxxx        xxxxx        xxxxxxxxxx    xxxx-xx-xx (xxx)                 xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
 
                                    xxxxxxxxxx    xxxx-xx-xx (xxx)                 xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
 
xxxxxxxxx  xxxx        xxxxx        xxxxxxxxxx    xxxx-xx-xx (xxx)                 xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
 
                                    xxxxxxxxxx    xxxx-xx-xx (xxx)                 xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
                                                                                   xxxxx xxx                xx           xxxx 
 
 
_____________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose. Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: S = Safety Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, Date, and Vital Sign (ordered as: Height, Weight, Temperature, Respiration Rate, Heart Rate, 
Systolic Blood Pressure, Diastolic Blood Pressure).