Conditions: Motion Sickness
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 316
Healthy volunteers: no

Brief summary:
A multi-center, randomized, double-blind, placebo-controlled study to investigate the efficacy of tradipitant in participants affected by motion sickness during travel

Detailed description:

Arms:
arm 1: None arm 2: None arm 3: None

Interventions: intervention 1: Tradipitant intervention 2: Placebo
Intervention descriptions: intervention 1: Oral Capsule intervention 2: Oral Capsule

Protocol document:
Prot_SAP_000.pdf: 
VP-VLY-686-3404 Amendment 2 
Vanda Pharmaceuticals Inc. 
Confidential 
 November 14, 2023  
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Motion Serifos: A randomized, double-blind, placebo-controlled 
study to investigate the efficacy of tradipitant in participants 
affected by motion sickness during travel 
 
 
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-686-3404 
Study Phase:  
 
 
 
 
 
III 
IND Number: 
 
 
 
 
 
141315 
NCT Number: 
 
 
 
 
 
NCT05903924 
 
Date:  November 14, 2023 
 
Status: Final 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Name of Sponsor/Company: 
Vanda Pharmaceuticals Inc. 
Name of Investigational Product: 
Tradipitant/VLY-686 
Name of Active Ingredient: 
Tradipitant/VLY-686 
Title of Study: Motion Serifos: A randomized, double-blind, placebo-controlled study to investigate 
the efficacy of tradipitant in participants affected by motion sickness during travel 
Study Center(s): Approximately 5-10 
Studied Period:  
First participant enrolled:  July 2023 
Estimated study duration: Twelve months 
Phase of Development:  
Phase III 
Number of Participants (planned): Approximately 300 affected participants will be randomized and 
assigned to tradipitant 85 mg, tradipitant 170 mg, or placebo in a 1:1:1 ratio. Treatment assignments 
will be made according to a randomization schedule.  
Diagnosis and Main Criteria for Inclusion: Adult males or females aged 18-75, inclusive, with a 
history of motion sickness who meet inclusion criteria. 
Investigational Product, Dosage and Mode of Administration: Tradipitant 170 mg PO, tradipitant 
85 mg PO, or placebo once approximately 60 minutes before entering the vehicle. 
Duration of Treatment: One boat trip lasting approximately 120-300 minutes on the moving vessel.  
Reference Therapy, Dosage and Mode of Administration: Placebo capsules will be provided in size 
and appearance identical to those containing tradipitant and will be administered orally. The 170 mg 
tradipitant dosage will consist of two tradipitant 85 mg capsules. The 85 mg tradipitant dosage will 
consist of one 85 mg tradipitant capsule and one placebo capsule. The placebo group will consist of two 
capsules matching in appearance to the 85 mg tradipitant capsules. 


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Primary Objectives:  
1. To assess the effects of tradipitant 85 mg and 170 mg on the prevention of vomiting from motion 
sickness during vehicle travel as measured by Vomiting Assessment (VA). 
Secondary Objectives:  
1. To assess the effects of tradipitant 85 mg and 170 mg on nausea severity as measured by 
subjective parameter Nausea Assessment (NA). 
2. To assess the effects of tradipitant 85 mg and 170 mg on the symptoms of motion sickness as 
measured by subjective parameter MSAQ. 
3. To assess the effects of tradipitant 85 mg and 170 mg on the symptoms of motion sickness as 
measured by subjective parameter PGI-S.  
4. To assess the safety and tolerability of a single oral dose of tradipitant 85 mg and 170 mg. 
Overall Design: This is a randomized, double-blind, placebo-controlled trial to investigate the efficacy 
and safety of a single 85 mg or 170 mg oral dose of tradipitant in motion sickness affected male and 
female participants during vehicle travel. 
 
The screening phase will consist of the participant taking the motion sickness eligibility questionnaire 
(MSEQ) to assess their susceptibility to motion sickness. Following this questionnaire, the participant 
will be interviewed to understand their history of motion sickness. If the participant meets pre-defined 
criteria as being eligible based on the motion sickness eligibility questionnaire and interview, they will 
proceed to the next step of a screening visit at a clinical site with a physician, and simultaneously, a lab 
visit for a blood draw. If the participant passes the medical visit screen and blood draw based on 
inclusion and exclusion criteria they will proceed to the evaluation phase.  
 
Eligible participants will be randomized 1:1:1 to tradipitant 85 mg, 170 mg, or placebo. Eligible 
participants will be instructed to take tradipitant 85 mg, 170 mg, or placebo approximately 60 minutes 
prior to entering the boat. Boat travel will last approximately 120-300 minutes. The Vomiting 
Assessment (VA) and Nausea Assessment (NA) questionnaires will be completed approximately every 
30 minutes of vehicle travel, and upon return to port. 
 
After the completion of the vehicle travel, the participant will complete the Patient Global Impression 
of Severity Questionnaire (PGI-S) and the Motion Sickness Assessment Questionnaire (MSAQ). 
All questionnaires will be submitted for analysis. Participants will then return for an EOS visit within 7 
days of Visit 2.  
Statistical Methods: Prevention of vomiting will be assessed by the VA, with the other questionnaires 
serving as secondary endpoints. The percentage of vomiting will be assessed by CMH test adjusting for 
the trips, and nausea severity measured by NA will be assessed by analysis of variance with the 
treatment group and trip as main effects. The primary efficacy analysis will be based on the ITT 
population.  
The statistical analyses will be detailed in the statistical analysis plan. 
 
 


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1. 
STATISTICS 
1.1. 
Sample Size and Accrual 
A sample size of 100 participants per arm (300 total) will provide around 96% power to detect 
a 26% difference in vomiting between tradipitant and placebo assuming 50% of participants on 
placebo will vomit and 24% of participants on tradipitant will vomit.  
1.2. 
Statistical Methods and Analysis Plan 
1.2.1. 
General 
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), which will be finalized 
prior to unblinding. Any changes in the statistical methods described in this protocol that occur 
prior to unblinding will be documented in the statistical analysis plan and will not require a 
protocol amendment.  
Statistical hypothesis testing will be performed at two sided alpha level of 0.05 unless specified 
otherwise. For continuous variables, population size (N for sample size and n for available 
data), the mean, the standard deviation (SD), the median, the minimum and maximum values 
will be tabulated.  For categorical variables, population size and frequencies in each category 
will be tabulated. 
Multiplicity adjustments will be used to control study wise type I error at 5%. The details will 
be provided in the SAP. 
1.2.2. 
Participant Populations for Analysis 
Three participant populations will be defined: 
Intent-To-Treat population (ITT population): Any participant randomized that received a dose 
of study drug and had post baseline VA data.  ITT population are analyzed as they are 
randomized, regardless of which treatment a participant received. 
Safety population (Safety population): Any participant randomized that received a dose of 
study drug. Safety population are analyzed based on the actual treatment received. 
Per-Protocol population (PP population): Any participant who was randomized and received 
the protocol required study drug exposure and required protocol processing. Blinded clinical 
data will be reviewed prior to data lock to finalize the list of PP population. 
The primary analyses will be performed in the intent-to-treat population. Analyses of efficacy 
endpoints in the PP population will provide supportive evidence. Safety summaries will be 
based on the Safety population. 
1.2.3. 
Participant Disposition 
Study completion and reasons for discontinuation for all randomized participants in the double-
blind phase will be summarized for each treatment group by simple tabulation. 
Discontinuations by reason will be tabulated by visit for each treatment group.  


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1.2.4. 
Demography and Other Baseline Data 
Demographic data will be tabulated by treatment group.  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.  
1.2.5. 
Study Medication 
Exposure and compliance will be tabulated by treatment groups. 
1.2.6. 
Prior/Concomitant Therapy 
Prior/concomitant therapy will be summarized. 
Any medications or therapy present before the first dose of study medication 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 participants from 
the Safety Set 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 participant will be counted only once. 
1.3. 
Efficacy Data Analysis 
1.3.1. 
Primary Outcome and Methodology 
The primary endpoint is the percentage of vomiting as assessed by the VA questionnaire.  The 
primary analysis method is CMH test adjusting for trips. The primary efficacy analysis will be 
based on the ITT population. 
As there are two active doses, the higher dose 170 mg will be tested first. Vomiting rate in the 
85 mg group will only be tested if the test in 170 mg group is positive.  
The statistical analyses will be detailed in the statistical analysis plan (SAP). 
1.3.2. 
Secondary Efficacy Analysis 
The continuous secondary endpoints from NA as well as those from other questionnaires 
(MSAQ, PGI-S) will be analyzed by an analysis of variance (ANOVA) model with the main 
effects of treatment group and trip. The categorical secondary endpoints will be analyzed in the 
same way as the primary endpoint. Other statistical methods may also be used as deemed 
appropriate.  The details will be provided in the SAP. 
1.4. 
Safety Data Analysis 
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.  


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Treatment-emergent adverse events will be summarized by presenting for each group the 
number and percentage of participants having any treatment-emergent AE, having an AE in 
each body system, and having each individual AE. (Note: In any given category [e.g. body 
system] a participant will only be counted once.) Similar displays will be provided for prior 
(conditions ending prior to the first dose of study medication) and current (conditions present 
while on study medication) medical conditions. 
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 participants experiencing SAEs and AEs resulting in discontinuation from 
the study will also be summarized. 
1.4.2. 
Laboratory Data 
The summary statistics of raw data (hematology and chemistry) and change from baseline 
values (means, medians, standard deviations, ranges) 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 participants 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 participants with clinically notable abnormalities. Clinically notable values 
(Appendix 20.1) 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). 
1.4.3. 
Vital Signs and Body Measurements 
Data from vital signs will be listed, clinically notable values as previously defined (Section 
11.1.3) will be flagged, and any other information collected will be listed. Data will be 
summarized by group using mean change from baseline and proportions of participants 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 participant. These data will also be summarized 
for each treatment group by presenting participants with ECG abnormalities; shift tables; 
summary statistics of raw data and change from baseline values (means, medians, standard 
deviations, ranges). 
1.5. 
Subgroup Analysis 
Subgroup analysis (such as, gender, age, race etc.) for efficacy variables and safety variables 
may be conducted. 


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1.6. 
Interim Analysis 
No interim analysis 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.