VP-VLY-686-1301: A Single Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of Tradipitant on Satiation, Gastric Volume, Gastric Accommodation and Gastric Emptying in Healthy Volunteers
Phase: PHASE1
Conditions: Healthy Volunteer
Sponsor: Vanda Pharmaceuticals

VP-VLY-686-1301                                                                              Vanda Pharmaceuticals Inc. 
Amendment No. 2 to the Clinical Study Protocol                                10 May 2021       
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CONFIDENTIAL 
 
 
TRADIPITANT  
AMENDMENT NO. 2 TO PROTOCOL VP-VLY-686-1301 
 
A SINGLE CENTER, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED STUDY TO EVALUATE THE 
EFFECTS OF TRADIPITANT ON SATIATION, GASTRIC 
VOLUME, GASTRIC ACCOMODATION AND GASTRIC 
EMPTYING IN HEALTHY VOLUNTEERS  
 
Author: 
Michael Camilleri, M.D. 
Jesse L. Carlin, Ph.D  
Document Type:  
 
 
 
 
Clinical Study Protocol 
Sponsor:  
 
 
 
 
 
 
Vanda Pharmaceuticals Inc. 
 
 
 
 
 
 
 
 
 
 
2200 Pennsylvania Ave. NW 
 
 
 
 
 
 
 
 
 
 
Suite 300E 
 
 
 
 
 
 
 
 
 
 
Washington, DC 20037 
USA 
 
 
Principle Investigator:  
 
 
Michael Camilleri, M.D. 
Co Investigators:  
 
 
 
 
Dan Maselli M.D., Jessica Atieh M.D. 
Study Product:  
 
 
 
 
tradipitant (VLY-686) 
Protocol Number: 
 
 
 
 
VP-VLY-686-1301 
Study Phase:  
 
 
 
 
 
I 
IND Number: 
 
 
 
 
 
131545 
 
 
Date:  10 May, 2021 
Status: Final 
Number of Pages: 68 

VP-VLY-686-1301                                                                              Vanda Pharmaceuticals Inc. 
Amendment No. 2 to the Clinical Study Protocol                                10 May 2021       
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CONFIDENTIAL 
SIGNATURE PAGE FOR VANDA PHARMACEUTICALS INC. 
 
Amendment No. 2 to VP-VLY-686-1303
 
Approved by the following: 
 
Program Lead: 
 
  
 
Jesse L. Carlin, Ph.D.  
 Date 
 
Clinical Project Lead 
 
 
  
 
 
  
Medical Director: 
 
  
 
Christos Polymeropoulos, M.D. 
 Date 
 
Medical Director 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

VP-VLY-686-1301                                                                              Vanda Pharmaceuticals Inc. 
Amendment No. 2 to the Clinical Study Protocol                                10 May 2021       
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CONFIDENTIAL 
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: VP-VLY-686-1301: A Single-Center, Placebo-Controlled, Double-Blind Study to 
Evaluate the Effects of Tradipitant on Satiation, Gastric Volume, Gastric Accommodation and Gastric 
Emptying in Healthy Volunteers 
Study center(s): Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo 
Clinic,  Rochester, MN  
Indication:  Healthy Volunteers 
Phase of development: I 
Number of subjects (planned):  Approximately 36 patients will be screened in order to fully complete 
the testing of 24 healthy subjects.  
Inclusion Criteria: 
1. Male and female subjects aged 18  65 years (inclusive); 
2. No medical problems or chronic diseases, specifically, no type 2 diabetes mellitus. 
3. 
35 kg/m2 (BMI = weight (kg)/ [height (m)]2);  
4. Subjects must agree to the following study restrictions:   
5. Males of procreative capacity (not surgically sterile) 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 
sterilized or post-menopausal partner;  
6. 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 1 month prior to 
randomization (or screening, if earlier) through 1 month following the last dose of study 
medication. Examples of acceptable methods of contraception for females include abstinence, 
double barrier method, IUD, hormonal contraception, or sterilized partner;  
7. Ability and acceptance to provide written informed consent;  
8. Willing to participate in the pharmacogenomics sample collection; 
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. 
Exclusion Criteria: 
11. Unable or unwilling to provide informed consent or to comply with study procedures. 
12. Unwilling to agree to provide pharmacogenomics sample
13. Diagnosis of gastrointestinal diseases. 
14. Structural or metabolic diseases that affect the GI system. 

VP-VLY-686-1301                                                                              Vanda Pharmaceuticals Inc. 
Amendment No. 2 to the Clinical Study Protocol                                10 May 2021       
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CONFIDENTIAL 
15. Unable to avoid the following over-the-counter medications 48 hours prior to the receipt 
of study medication and throughout the study: 
16. Medications that alter GI transit including laxatives, magnesium and aluminum 
containing antacids, prokinetics, erythromycin;  
17. Analgesic drugs including NSAIDs and COX-2 inhibitors 
NOTE:  Stable doses of thyroid replacement, estrogen replacement, low-dose aspirin for 
cardioprotection, and birth control are permissible.   
18. History of recent surgery (within 60 days of screening). 
19. Pregnant or nursing;  
20. History of intolerance and/or hypersensitivity to medications similar to tradipitant and its 
accompanying excipients; 
21. History (including family history) or current evidence of congenital long QT syndrome or 
known acquired QT interval prolongation (including QTcF > 450 in males or > 470 in females 
at screening); 
22. History of suicide attempt and/or suicidal ideation (of type 4 or 5 on the Columbia Suicide 
Severity Rating Scale (C-SSRS)) within 2 years of screening or subject is at risk of suicide at 
Screening or Baseline visits, in the opinion of the investigator;  
23. Recent history (within six months of screening) of Alcohol Use Disorder or Substance Use 
Disorder which may include a positive drug screen at the Screening visit; 
24. Acute or chronic illness or history of illness, which in the opinion of the investigator could pose 
a threat or harm to the subject or obscure interpretation of laboratory test results or interpretation 
of study data such as frequent angina, Class III or IV congestive heart failure, any impairment of 
renal or hepatic function, poorly controlled diabetes, etc; 
25. Indication of impaired liver function (including values for AST, ALT, or bilirubin > 2 times the 
Upper Limit of Normal, unless isolated bilirubin > 2 
 
26. Has a creatinine level > 2x ULN; 
27. Anyone affiliated as a member of the investigative team or sponsor and/or anyone who may 
consent under duress;  
28. 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:  
Oral 85 mg tradipitant and matching placebo capsules will be administered from Mayo 
Research Pharmacy. Subjects will be randomized to one of two treatment arms to receive 85 
mg tradipitant BID or placebo. 
Duration of treatment:  Up to 9 days 
Objectives:  
Primary:  

VP-VLY-686-1301                                                                              Vanda Pharmaceuticals Inc. 
Amendment No. 2 to the Clinical Study Protocol                                10 May 2021       
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CONFIDENTIAL 
To evaluate the effects of tradipitant relative to placebo in healthy volunteers in the 
following: 
 Difference in fasting GV 
 Difference in postprandial GV and in accommodation volume (that is, postprandial 
minus fasting gastric volumes) 
 Difference in gastric emptying (T1/2, emptying at 2h and emptying at 4h) 
 Volume to fullness (sensation of usual postprandial fullness) and maximum feeling 
of fullness (MTV). 
 
Secondary: 
 Absolute postprandial gastric volume 
 Gastric volume (GV) ratio (postprandial/fasting GV) 
 
 Gastric emptying of solids at 2h 
 Gastric emptying of solids at 4h 
Intragastric meal distribution at time zero, (IMD0) following ingestion of test meal
 Maximum tolerated volume (MTV) during satiation test 
 Aggregate symptoms score 30 min after MTV on satiation test  
 Individual symptom scores (nausea, bloating, fullness, pain) on satiation test 
  
Overall Design: 
This is a randomized, double-blind, placebo-controlled, single center study during which 
healthy volunteers will be recruited, enrolled, and randomized to one of 2 treatment groups.  
Subjects meeting all inclusion/exclusion criteria will be randomized to either placebo or 
tradipitant, two 85mg tablet daily (b.i.d.) for 9 consecutive days. Subjects may be involved in 
study activity for up to five weeks from screening date to completion of all studies. The actual 
study related testing will be conducted on three days. 
 
Enrollment of subjects will continue until N=24 of those that have been randomized to study 
medication and have completed all study testing through Day 9.  Subjects who withdraw 
consent after being randomized will be included in an intent-to-treat analysis with missing data 
imputed based on data of completed subjects.  Subjects that withdraw from participation before 
receipt of medication will be replaced. Subjects who have started their assigned study 
medication, but do not complete all the study testing  through Day 9 will be replaced. 
Primary Endpoint:  
The primary objectives of this study are: 
 Comparison of fasting gastric volume induced by tradipitant vs. placebo studied by 
single photon emission computed tomography (SPECT) 
 Comparison of accommodation volume induced by tradipitant vs. placebo studied by 
SPECT 
 Comparison of volume to fullness (VTF,mL) on satiation test for tradipitant vs. 
placebo 
 Comparison of gastric emptying T1/2 of solids on scintigraphy for tradipitant vs. 
placebo 
 Comparison of gastric emptying values at 2 and 4 hours 

VP-VLY-686-1301                                                                              Vanda Pharmaceuticals Inc. 
Amendment No. 2 to the Clinical Study Protocol                                10 May 2021       
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CONFIDENTIAL 
Criteria for evaluation: 
Efficacy:  
 Single photon emission computed tomography (SPECT) to calculate fasting gastric 
volume and postprandial gastric accommodation  
 Measurement of volume to fullness (mL) on satiation test  
 Gastric emptying by scintigraphy 
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. 
Sample Size Discussion:  
Sample size is based on the results of primary endpoints in the Mayo Clinic lab. Expected  
23.6% in the gastric accommodation volume and 29.2% in gastric emptying T1/2, based 
on the coefficients of variation observed from the Mayo Clinic laboratory in prior studies.