Clinical trial NCT02651714
Conditions: Atopic Dermatitis
Keywords: eczema chronic pruritus
Sponsor: Vanda Pharmaceuticals
Start date: 2016-01-19; Completion date: 2017-08-04
Enrollment: 168 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a multicenter, randomized, double-blind, placebo-controlled study to be conducted in the United States in subjects with treatment-resistant pruritus diagnosed with atopic dermatitis.

Detailed description:

Arms: arm 1: Oral arm 2: Oral
Interventions: intervention 1: Tradipitant intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_000.pdf: 
 
 
TRADIPITANT 
VP-VLY-686-2102 
 
 
A 
MULTICENTER, 
RANDOMIZED, 
DOUBLE-BLIND, 
PLACEBO-CONTROLLED STUDY TO ASSESS THE 
SAFETY 
AND 
EFFICACY 
OF 
TRADIPITANT 
IN 
TREATMENT-RESISTANT PRURITUS ASSOCIATED WITH 
ATOPIC DERMATITIS 
 
Document Type:  
 
 
 
 
Clinical Study Protocol 
Sponsor:  
 
 
 
 
 
 
Vanda Pharmaceuticals Inc. 
 
 
 
 
 
 
 
 
 
 
2200 Pennsylvania Ave. NW 
 
 
 
 
 
 
 
 
 
 
Suite 300E 
 
 
 
 
 
 
 
 
 
 
Washington, DC 20037 
USA 
Study Product:  
 
 
 
 
tradipitant (VLY-686) 
Protocol Number: 
 
 
 
 
VP-VLY-686-2102 
Study Phase:  
 
 
 
 
 
II 
IND Number: 
 
 
 
 
 
122741 
NCT Number: 
 
 
 
 
 
NCT02651714 
 
 
Date:  
03 March 2017 
Status: 
Final 


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SYNOPSIS 
Name of Sponsor/Company: 
Vanda Pharmaceuticals Inc. 
Name of Investigational Product: 
Tradipitant (VLY-686) 
Name of Active Ingredient: 
{2-[1-(3,5-Bistrifluoromethylbenzyl)-5-pyridin-4-yl-1H-[1,2,3]triazol-4-yl]-pyridin-3-yl}-(2-
chlorophenyl)-methanone 
Title of Study: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess 
the Safety and Efficacy of Tradipitant in Treatment-Resistant Pruritus Associated with Atopic 
Dermatitis  
Study center(s): Up to 30 centers in the United States 
Indication:  
Chronic pruritus in subjects with atopic dermatitis 
Phase of development:  
II 
Number of subjects (planned):  
Approximately 164 subjects randomized (82 per arm, 1:1 randomization scheme)  
Inclusion Criteria: 
1. Male and non-pregnant, non-lactating female subjects aged 18 – 65 years (inclusive); 
2. Diagnosed with atopic dermatitis 
a. with a SCORAD index ≤ 80 at the screening and baseline visits; 
b. with atopic lesion(s) present at the screening and baseline visits; 
3. Suffering from chronic pruritus with pruritus being actively present for at least 6 weeks 
prior to screening despite the use of antihistamines or corticosteroids; 
4. Average pruritus intensity (VAS) ≥70 mm (during one of the three days preceding the 
screening and baseline visits ); 
5. Patient assessment of pruritus (VRS (1-5) item “pruritus”) ≥3 at screening and baseline 
visits; 
6. Subjects with Body Mass Index (BMI) of ≥18 and ≤35 kg/m2 (BMI = weight (kg)/ [height 
(m)]2);  
7. Subjects must agree to the following study restrictions:   
a. Males of procreative capacity (not surgically sterile via vasectomy) will use an 
acceptable method of contraception from randomization through 1 month 
following the last dose of study medication. Examples of acceptable 
contraception for males include abstinence, use of a barrier method, or surgically-
sterilized or post-menopausal partner.  
b. Females of child-bearing potential (not surgically sterile or post-menopausal, 
defined as 12 months without menses) will use an acceptable method of 
contraception from the earlier of screening or 1 month prior to randomization 


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through 1 month after the last dose of study medication. Examples of acceptable 
methods of contraception for females include abstinence, the use of 2 independent 
barrier methods, or hormonal contraception plus 1 barrier method, or surgically 
sterilized partner.  
8. Ability to provide written informed consent;  
9. Willing and able to comply with all study requirements and restrictions; 
10. Willing to not participate in any other interventional trial for the duration of their 
participation; 
11. Subjects must be in good health as determined by past medical history, physical 
examination, electrocardiogram, clinical laboratory tests and vital signs. 
 
Exclusion Criteria: 
1. Chronic pruritus due to condition other than atopic dermatitis (AD)  
2. Superinfection of AD; 
3. Unwilling or unable to follow medication restrictions described in Section 7.2, or 
unwilling or unable to sufficiently washout from use of restricted medication.  
4. Under medical treatment for a skin disease with a therapy listed in the prohibited 
medications section that may influence the results of the study; or treatment with 
Cyclosporin A within the past 6 months.   
5. Recent history (within six months of screening) of Alcohol Use Disorder or Substance 
Use Disorder as defined in DSM-5 or a positive drug screen at the Screening visit; 
6. Subject has ever made a suicide attempt and/or had suicidal ideation of type 4 or 5 on the 
Columbia Suicide Severity Rating Scale (C-SSRS) or subject is at risk of suicide at 
Screening or Baseline, in the opinion of the investigator;  
7. Any medical procedure requiring general anesthetic within three months of the Baseline 
Visit or any procedure requiring sedation within one month of the baseline visit; 
8. Current clinically significant cardiovascular, respiratory, 
neurologic, hepatic, 
hematopoietic, renal, gastrointestinal or metabolic dysfunction unless currently controlled 
and stable, including (but not limited to) the following: 
a. Uncontrolled diabetes mellitus defined as HbA1c >7%; 
b. Positive hepatitis C antibody test (anti-HCF); 
c. Positive hepatitis B surface antigen (HBsAg); 
9. History (including family history) or current evidence of congenital long QT syndrome 
or known acquired QT interval prolongation; 
10. Exposure to any investigational medication, including placebo, within 60 days of the 
Baseline Visit;  
11. History of intolerance and/or hypersensitivity to medications similar to tradipitant and its 
accompanying excipients; 


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12. Participation in a previous tradipitant (LY686017 or VLY-686) trial; 
13. Indication of impaired liver function (including values for AST, ALT, or bilirubin > 1.5 
times the Upper Limit of Normal, unless isolated bilirubin > 1.5 x ULN due solely to 
Gilbert’s syndrome); 
14. Has a creatinine level > 1.25x ULN; 
15. Anyone affiliated with the site or sponsor and/or anyone who may consent under duress; 
16. Any other reason as determined by the Investigator which may lead to an unfavorable 
risk-benefit of study participation, may interfere with study compliance, or may confound 
study results.  
Investigational product, dosage and mode of administration:  
A single oral capsule of tradipitant 85 mg or matching placebo will be orally administered twice 
daily for a total daily dose of 170 mg.  Study medication should be administered with food. 
Duration of treatment:  8 weeks 
Objectives:  
Primary:  
• To evaluate the efficacy of tradipitant relative to placebo in reducing 
symptoms of chronic pruritus in subjects with atopic dermatitis  
Secondary: 
 
• 
To evaluate the efficacy of tradipitant relative to placebo in reducing chronic 
pruritus  
• 
To evaluate the efficacy of tradipitant relative to placebo in reducing atopic 
dermatitis disease progression  
• 
To evaluate the efficacy of tradipitant relative to placebo in reducing the severity 
of sleep disruption 
• 
To assess the efficacy of tradipitant on global measures of improvement  
• 
To assess the efficacy of tradipitant on  quality of life  
• 
To evaluate the relationship between tradipitant’s pharmacokinetics and efficacy 
measurements 
• 
To explore the safety and tolerability of multiple oral doses of tradipitant. 
 
Optional Pharmacogenetic Sub-Study: 
• 
To identify genetic markers that correlate with response to tradipitant treatment. 
• 
To identify genetic markers that correlate with adverse events that may occur 
upon treatment with tradipitant. 
• 
To identify genetic markers that are associated with atopic dermatitis and/or 
pruritus and disorders/diseases associated with NK-1 receptors. 
• 
To identify genetic markers that are associated in the metabolism, distribution, 
and/or excretion of tradipitant and its metabolites.     
Overall Design: 


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This is a multicenter, randomized, double-blind, placebo-controlled study to be conducted in the 
United States. Approximately 164 subjects with treatment-resistant pruritus diagnosed with atopic 
dermatitis, who satisfy the selection criteria for the study, will be randomized to receive either 
tradipitant 85 mg or matching placebo BID.  
The study is divided into two phases: the pre-treatment phase and the evaluation phase. The pre-
treatment phase includes a screening and a baseline visit where subjects’ eligibility for the study 
will be assessed. Washout of medications per Section 7.2 will occur during the screening phase.  
The evaluation phase includes 8 weeks of randomized double-blind treatment. In clinic 
evaluations will occur at Screening, Baseline, and Weeks 2, 4, 6, and 8. 
Criteria for evaluation: 
Efficacy:  
Efficacy assessments will include:  
• 
Daily Diary Itch Scale (DDIS) 
• 
Pruritus Visual Analogue Scale (VAS)   
• 
Verbal Rating Scale (VRS) item “pruritus”  
• 
SCORing Atopic Dermatitis (SCORAD) index  
• 
Eczema Area Scoring Index (EASI)  
• 
Daily Diary Sleep Scale (DDSS) 
• 
Clinical Global Impression of Change (CGI-C) 
• 
Patient Global Impression of Change (PGI-C) 
• 
Skindex-16 
• 
Patient Benefit Index (PBI) 
Safety:  
• 
Safety and tolerability assessments will include the recording of adverse events 
(AEs), physical examinations, clinical laboratory evaluations, vital signs, and 
electrocardiograms. 
• 
The Columbia-Suicide Severity Scale (C-SSRS) will be used to assess suicidal 
behavior and ideation. 
Statistical methods:  
Primary Endpoint:  
 
• 
Mean change from baseline in pruritus symptoms in the tradipitant group versus the 
placebo group  
Secondary Endpoints:   
• 
Mean change from baseline in pruritus intensity in the tradipitant group versus the 
placebo group  


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• 
Mean change from baseline of disease severity in the tradipitant group versus the 
placebo group as measured by SCORing Atopic Dermatitis (SCORAD) index  
• 
Mean change from baseline of disease severity in the tradipitant group versus the 
placebo group as measured by Eczema Area Scoring Index (EASI)  
• 
Mean change from baseline in the daily diary sleep scale(DDSS) in the tradipitant 
group versus the placebo group. 
• 
Mean global improvement measured by the Clinical Global Impression-Change 
(CGI-C), Patient Global Impression of Change (PGI-C), Skindex-16, and the Patient 
Benefit Index (PBI)  
• 
Mean change from baseline in pruritus intensity in relation to serum concentrations 
of tradipitant and its metabolites.  
 
Statistical analyses will be performed using two-sided tests.  The details of analysis models will 
be specified in the SAP.  
 
 
 


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Table 1: 
Schedule of Evaluations 
Phase 
Pre-Treatment  
Evaluation 
Visit 
V1 
Screening 
V2 
Baseline 
V3 
 
V4 
 
V5 
 
V6  
EOS or 
ET 
Study Day 
Up to Day 
-45 
Day 0 
Day 141 
Day 281 
Day 421 
Day 561 
or ET 
Informed Consent Form (ICF)2 
X 
 
 
 
 
 
Eligibility assessment  
X 
X 
 
 
 
 
Subject demography 
X 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
Prior/concomitant medications 
X 
X 
X 
X 
X 
X 
Adverse Event (AE) assessment  
X3 
X 
X 
X 
X 
X 
Serum β-HCG (for WOCBP) 
X 
 
 
 
 
X 
Urine pregnancy test (for WOCBP) 
 
X 
X 
X 
X 
 
HbA1c 
X 
 
 
 
 
 
Hepatitis B/C screen 
X 
 
 
 
 
 
Drug and alcohol screen 
X 
X 
 
X 
 
X 
Hematology, chemistry, and urinalysis 
X 
X 
 
X 
 
X 
IgE 
 
X 
 
 
 
 
Pharmacogenetic (PG) sample4 
 
X 
 
 
 
 
Pharmacokinetic (PK) sample(s) 
 
X 
X5 
X6 
X5 
X5 
12-lead resting ECG 
X 
X 
X 
X 
X 
X 
Vital signs and body measurements7 
X 
X 
X 
X 
X 
X 
Physical Examination (PE) 
X 
X8 
X8 
X8 
X8 
X 
C-SSRS9 
X 
X 
X 
X 
X 
X 
Medical History of Pruritus Questionnaire 
 
X 
 
 
 
 
Pruritus Assessment (incl. VAS, VRS)10 
X 
X 
X11 
X12 
X 
X 
SCORing Atopic Dermatitis (SCORAD) 
X 
X 
X 
X 
X 
X 
Eczema Area and Severity Index (EASI) 
X 
X 
X 
X 
X 
X 
Patient Benefit Index (PBI)13 
 
X 
X 
X 
X 
X 
Skindex-16  
 
X 
X 
X 
X 
X 
Patient Global Impression of Change (PGI-C) 
 
 
X 
X 
X 
X 
Clinical Global Impression of Change (CGI-C) 
 
 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
Study medication dispensation14 
 
X 
X 
X 
X 
 


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Phase 
Pre-Treatment  
Evaluation 
Visit 
V1 
Screening 
V2 
Baseline 
V3 
 
V4 
 
V5 
 
V6  
EOS or 
ET 
Study Day 
Up to Day 
-45 
Day 0 
Day 141 
Day 281 
Day 421 
Day 561 
or ET 
Study medication collection & compliance 
 
 
X 
X 
X 
X 
Subject daily diary distribution and instruction 
X15 
 
 
 
 
 
Subject daily diary review 
 
X 
X 
X 
X 
X 
Subject daily diary collection 
 
 
 
 
 
X 
 
EOS = End of Study; ET = Early Termination; WOCBP = Women of Child-bearing Potential; 
ECG = electrocardiogram; C-SSRS = Columbia Suicide Severity Rating Scale; VAS = Visual 
Analog Scale; VRS = Verbal Rating Scale 
1 within +/- 3 days 
2 Informed Consent will be obtained prior to performance of any study procedure(s) 
3 Adverse Event collection will begin at the time the ICF is signed.  
4 The PG blood sample will only be collected for subjects consenting to the PG study.  
5 The PK sample collection should occur within 15 minutes following the pruritus assessment 
6 Multiple PK samples will be collected at V4.  In-clinic dosing of study medication (morning dose) will occur at V4 
following a pre-dose PK blood draw.  
7 Vital signs will be collected at all visits.  Height will be collected at V1(Screening).  Body weight will be collected 
at V1 (Screening), V2 (Baseline), and V6. 
8 An abbreviated physical examination may be performed at V2 (Baseline), V3, V4, and V5 if clinically indicated. 
9 The Screening/Baseline C-SSRS will occur at V1 (Screening). The Since Last Visit C-SSRS will occur at all other 
visits. 
10 The baseline pruritus assessment will be completed at V1 and V2.  The post-baseline pruritus assessment will be 
completed at V3, V4, V5, and V6. 
11 At V3, V5, and V6, the Pruritus Assessment will be conducted between 2 and 4 hours post study drug administration 
12 At V4, the Pruritus assessment will occur at 03:00 (+/- 00:30) post in-clinic study drug administration  
13 At V2 (Baseline), The Patient Needs Questionnaire (PBI-PNQ) will be administered.  The Patient Benefits 
Questionnaire (PBI-PBQ) will be administered at subsequent visits.  
14 Subjects will be instructed to take their first dose of study medication on the evening of Day 0.   
15 The subject diary will be completed for at least 7 days prior to randomization and the duration of the evaluation 
phase.  

SAP_001.pdf: 
 
 
TRADIPITANT 
VP-VLY-686-2102 
 
 
A 
MULTICENTER, 
RANDOMIZED, 
DOUBLE-BLIND, 
PLACEBO-CONTROLLED STUDY TO ASSESS THE 
SAFETY 
AND 
EFFICACY 
OF 
TRADIPITANT 
IN 
TREATMENT-RESISTANT PRURITUS ASSOCIATED WITH 
ATOPIC DERMATITIS 
 
Document Type:  
 
 
 
 
Statistical Analysis Plan 
Sponsor:  
 
 
 
 
 
 
Vanda Pharmaceuticals Inc. 
 
 
 
 
 
 
 
 
 
 
2200 Pennsylvania Ave. NW 
 
 
 
 
 
 
 
 
 
 
Suite 300E 
 
 
 
 
 
 
 
 
 
 
Washington, DC 20037 
USA 
Study Product:  
 
 
 
 
tradipitant (VLY-686) 
Protocol Number: 
 
 
 
 
VP-VLY-686-2102 
Study Phase:  
 
 
 
 
 
II 
IND Number: 
 
 
 
 
 
122741 
NCT Number: 
 
 
 
 
 
NCT02651714 
 
 
Date:  
03 March 2017 
Status: 
Final 
 


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1. 
STATISTICS 
1.1. 
Sample Size and Accrual 
The sample size chosen for this study is not based on statistical considerations.  This sample size 
was chosen after taking into consideration historical data Approximately 164 patients will be 
randomized. 
1.2. 
Statistical Methods and Analysis Plan 
This section describes the planned statistical analyses in general terms.  A complete description of 
the methodology will be specified in a statistical analysis plan (SAP). Any changes in the 
statistical methods described in this protocol that occur prior to database lock will be documented 
in the SAP and will not require a protocol amendment.  
 
1.2.1. 
General 
Statistical analyses will be performed using two-sided tests.   
 
Data will be summarized by treatment group (and by visit when applicable), with respect to 
demographic and baseline characteristics, efficacy variables, and safety variables. 
 
Summary statistics will include the mean, N, standard deviation, median, minimum, and 
maximum values for continuous variables, and frequencies and percentages for categorical 
variables. 
 
For the analyses of change from baseline, only subjects with a baseline and at least one (1) post-
baseline measure will be included in the analysis. Unless otherwise specified, baseline is defined 
as the latest non-missing observation across all the visits in the screening phase, before the active 
study drug begins. Endpoint will be the latest non-missing observation across all the post-baseline 
visits in the evaluation phase. 
 
Low enrolling sites will be pooled for analysis and the pooling algorithm will be determined prior 
to breaking the blind.  The goal of pooling low enrolling sites is to have a sufficient number of 
subjects per treatment group within a site for the analysis models and for the evaluation of the 
treatment-by-site interaction for the primary endpoint.  Unless otherwise specified, the pooled 
sites will only be used in the analyses where site has an effect.  The actual sites rather than the 
pooled sites will be specified in data listings. 
 
 


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Details of the model and the analyses will be specified in the SAP.  All statistical analyses will be 
performed using SAS®, Version 9.1.3 or higher. 
 
1.2.2. 
Subject Populations for Analysis 
The following analysis populations will be defined for this study: 
Intent-to-Treat: will include any subject randomized into the study that receives a dose of 
study drug and that has completed at least one post-baseline efficacy measurement while on 
study medication;   
Safety: Any subject randomized into the study that receives a dose of study drug; 
Per-Protocol: Any subject who is randomized and receives the protocol required study drug 
exposure and required protocol processing.   
 
Efficacy analyses will be performed on the Intent-to-Treat population and the Per-Protocol 
population.  Safety summaries will be based on Safety set.  Subject characteristics will be 
presented for all subjects randomized. 
 
1.2.3. 
Subject Disposition 
Study completion and reasons for discontinuation for all randomized subjects in the double-blind 
phase will be summarized for each treatment group.    Discontinuations by reason will be tabulated 
by visit for each treatment group. 
 
Time to discontinuation due to adverse events, lack of efficacy and for any reason will be analyzed 
using Kaplan-Meier survival techniques; the log-rank test will be used for group comparison. 
 
1.2.4. 
Demography and Other Baseline Data 
Demographic data and subject characteristics at screening/baseline will be listed and summarized 
by treatment group for all randomized subjects using descriptive statistics. 
 
Past and current medical history will be summarized by treatment group using the system organ 
class (SOC) as coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding 
dictionary.  
 
Past medical conditions will be defined as an onset date prior to randomization (Visit 2) and 
resolved (not on-going) as of Visit 2.  Current medical conditions, defined as an onset date on or 
after the date of randomization (Visit 2) or an onset date prior to randomization (Visit 2) and 
unresolved (on-going) as of Visit 2, will be reported separately, but similarly to the past medical 


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conditions.  If both a past and a current (on-going) medical condition record are indicated for a 
condition, the condition will be presented under current medical conditions only. 
 
1.2.5. 
Study Medication 
The number of subjects at each visit will be summarized by treatment group.  
 
The compliance to study medication, as recorded in the CRF, will also be summarized by 
treatment group. The proportion of subjects who are significantly noncompliant in the double-
blind phase, as noted in Section 7.3 of this protocol, will be summarized by treatment groups. 
 
1.2.6. 
Prior/Concomitant Therapy 
Any medications or therapy present before the first dose of study medication (Visit 2) will be 
considered as prior medications.  Concomitant medications (medications present while on study 
medication) will be recorded throughout the study and at early discontinuation.  These 
medications will be coded using the WHO-drug dictionary.  The number of subjects from the 
Safety Population using prior or concomitant medications will be categorized by the WHO-drug 
category and preferred term, and presented for each treatment group.  In any given category (e.g., 
drug category) a subject will be counted only once. 
 
1.3. 
Efficacy Data Analysis 
1.3.1. 
Primary Outcome  and Methodology 
The primary efficacy outcome measure for the double-blind phase will be the mean change from 
baseline in pruritus symptoms.  A detailed description of the primary analysis model will be 
included in the SAP.  
 
 
As stated previously, any changes in the statistical methods that occur prior to database lock will 
be documented in the SAP and will not require a protocol amendment. 
  
1.3.2. 
Secondary Efficacy Analysis 
The secondary efficacy outcomes include: 
• DDSS 
• Itch questionnaires including VAS, VRS, DDIS 
• SCORAD index; 


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• Objective SCORAD; 
• EASI;  
• PGI-C; 
• CGI-C; 
• PBI; 
• Skindex-16; 
• Pharmacokinetic-Pharmacodynamic correlation. 
 
Continuous endpoints will be summarized and analyzed in a manner similar to the primary 
endpoint. Details of the analysis will be described in the SAP. 
 
Categorical variables will be evaluated as described in the SAP.  Time to event data will be 
analyzed using the Kaplan-Meier method, and the treatment group differences will be tested by 
the log-rank test. Details of the analysis will be described in the SAP. 
1.4. 
Safety Data Analysis 
The primary assessment of safety will be based on the frequency of treatment-emergent adverse 
events (TEAEs), serious adverse events (SAEs) and on the frequency of clinically notable 
abnormal vital signs, electrocardiograms (ECGs) and laboratory values. Other safety evaluations 
include changes in vital signs, changes in clinical laboratory evaluations, and changes in ECGs, 
physical exam findings during treatment, and suicide ideation and behavior events. 
 
1.4.1. 
Adverse Events 
Adverse events will be recorded throughout the study and at early discontinuation. Adverse events 
and medical conditions will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) coding dictionary.  Treatment-emergent adverse events will be defined as those 
events, which are newly occurring or worsening from baseline.  In all cases only treatment 
emergent adverse events will be summarized.  
 
Treatment-emergent adverse events will be summarized within each treatment group by primary 
system organ class and preferred term. (NOTE: In any given category [e.g. body system] a subject 
will only be counted once.) The incidence rates of TEAEs will be analyzed as described in the 
SAP.  Similar displays will be provided for SAE and prior (conditions ending prior to the first 
dose of study medication and current (conditions present while on study medication) medical 
conditions. 
 


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Adverse events will further be categorized by severity, relationship to study medication, and action 
taken. Other information collected will be listed, as appropriate. Any event starting more than 3 
days after the final dose of study medication will be excluded from the above tables and only 
listed, unless the event caused discontinuation. 
 
The proportions of subjects experiencing SAEs and AEs resulting in discontinuation from the 
study will be summarized by treatment groups.  
 
1.4.2. 
Laboratory Data 
Clinical Laboratory Data 
The summary statistics of raw data (hematology and chemistry) and change from baseline values 
will be presented, as well as shift tables from baseline to post-baseline values using normal ranges.  
For urinalysis parameters, the number and percentage of subjects falling under each category of 
the test will be presented. 
 
Clinical laboratory data will be summarized for each treatment group by presenting the 
proportions of subjects with clinically notable abnormalities (Appendix 20.1). 
 
Clinically notable values will be identified according to the criteria identified in the FDA's 
"Supplementary Suggestions for Preparing an Integrated Summary of Safety Information in an 
Original NDA Submission and for Organizing Information in Periodic Safety Updates" (Revised 
2-APR-87) provided by the FDA Division of Neuropharmacological Drug Products (DNDP).  
Differences in incidence rates between the treatment groups will be tested as described in the SAP. 
 
1.4.3. 
Vital Signs and Body Measurements 
Data from vital signs and body measurements will be listed, clinically notable values (Appendix 
20.2) will be flagged, and any other information collected will be listed. Data will also be 
summarized by treatment group using mean change from baseline and proportions of subjects 
with values outside the normal range, and values that were clinically notable.  
 
1.4.4. 
Electrocardiogram (ECG) 
Results from the ECG will be listed for each subject. These data will also be summarized for each 
treatment group by presenting subjects with newly occurring or worsening ECG abnormalities. 
 
1.4.5. 
C-SSRS 
Results from the C-SSRS will be listed for each subject.  These data will also be summarized by 
treatment group and for suicidal ideation events, suicidal behaviors and completed suicides. In 
particular, for each of the following suicide related events, the number and percent of subjects 


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with the event will be enumerated by treatment group: completed suicide, nonfatal suicide attempt, 
interrupted attempt, aborted attempt, preparatory acts or behavior, active suicidal ideation with 
specific plan and intent, active suicidal ideation with some intent to act without specific plan, 
active suicidal ideation with any methods (no plan) without intent to act, non-specific active 
suicidal thoughts, and wish to be dead.  Details of the analysis will be provided in the SAP. 
 
1.5. 
Subgroup Analysis 
The subgroup analysis (such as, gender, age, baseline illness severity etc.) for efficacy variables 
and safety variables may be conducted as described in the SAP. 
 
1.6. 
Interim Analysis 
No interim analyses are planned. 
 
1.7. 
Deviations in Analysis from Statistical Plan and Other Issues 
During the analysis and reporting process, any deviations from the statistical plan designed for 
this protocol will be described and justified in the final report.