A Randomized Placebo-Controlled Study of the Neurokinin-1 (NK1) Receptor Antagonist Serlopitant Prurigo Nodularis (PN)

• Sponsor: Vyne Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02196324
• Collaborator: (none)
• Enrollment: 128
• Locations: 15
• Arms: 2
• Actual Duration (Months): 23.1
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate whether or not VPD-737, an NK1 receptor antagonist is safe and effective for treatment of prurigo nodularis versus placebo.

Condition or Disease	Intervention/Treatment	Phase
Prurigo Nodularis	Drug: serlopitant; Drug: Placebo	Phase 2

Detailed Description

The sensation of itch is transmitted to the brain through the nervous system. Several chemicals are involved in transmitting this signal.This trial of VPD 737 is intended to treat this condition by blocking one of the chemicals involved in the transmission of the itch signal. This is an oral drug administered once daily It has been used in other trials and has shown to be safe at the doses used in this trial. The trial will involve once daily pills for 8 weeks. Subject will be asked to fill out questionnaires both electronically and on paper during the study period. Patients will also be monitored for safety and will have blood taken for testing and several points during the trial. Overall participation will last about 14 weeks

Study Design

• Study Type: Interventional
• Actual Enrollment: 128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Study of Neurokinin-1 Receptor Antagonist Serlopitant in Subjects With Prurigo Nodularis
• Actual Study Start Date: Jul 9, 2014
• Actual Primary Completion Date: May 27, 2016
• Actual Study Completion Date: Jun 10, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: serlopitant 5 mg tablets serlopitant 5 mg tablets	Drug: serlopitant; NK1 receptor antagonist; Other Names: VPD-737
Placebo Comparator: Placebo tablets Placebo tablets	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Average Visual Analog Scale at Baseline [At Baseline]

   At study visits, participants recorded a mark for pruritus severity on a 10-cm horizontal line. This thermometer-type scale was marked with ratings of "no itch" (0 cm) and worst imaginable itch" (10 cm). Average Visual Analog Scale (VAS) (average itch over the past 24 hours) was recorded. Higher scores indicated worse outcome.

2. Average Visual Analog Scale at Week 2 [At Week 2]

   At study visits, participants recorded a mark for pruritus severity on a 10-cm horizontal line. This thermometer-type scale was marked with ratings of "no itch" (0 cm) and worst imaginable itch" (10 cm). Average VAS (average itch over the past 24 hours) was recorded. Higher scores indicated worse outcome.

3. Average Visual Analog Scale at Week 4 [At Week 4]

   At study visits, participants recorded a mark for pruritus severity on a 10-cm horizontal line. This thermometer-type scale was marked with ratings of "no itch" (0 cm) and worst imaginable itch" (10 cm). Average VAS (average itch over the past 24 hours) was recorded. Higher scores indicated worse outcome.

4. Average Visual Analog Scale at Week 8 [At Week 8]

   At study visits, participants recorded a mark for pruritus severity on a 10-cm horizontal line. This thermometer-type scale was marked with ratings of "no itch" (0 cm) and worst imaginable itch" (10 cm). Average VAS (average itch over the past 24 hours) was recorded. Higher scores indicated worse outcome.

Secondary Outcome Measures

1. Number of Participants With Improvement in Pruritus as Reported on Verbal Rating Scale (VRS) - Pruritus [At Baseline and Week 8]

   At study visits, participants used the VRS to rate their skin sensations (pruritus, burning, and stinging) using a 5-point scale (0 = not present; 1 = mild present; 2 = moderately present; 3 = severely present; and 4 = very severely present). Higher scores indicated worse outcome.

2. Number of Participants With Improvement in Burning as Reported on Verbal Rating Scale (VRS) - Burning [At Baseline and Week 8]

   At study visits, participants used the VRS to rate their skin sensations (pruritus, burning, and stinging) using a 5-point scale (0 = not present; 1 = mild present; 2 = moderately present; 3 = severely present; and 4 = very severely present). Higher scores indicated worse outcome.

3. Number of Participants With Improvement in Stinging as Reported on Verbal Rating Scale (VRS) - Stinging [At Baseline and Week 8]

   At study visits, participants used the VRS to rate their skin sensations (pruritus, burning, and stinging) using a 5-point scale (0 = not present; 1 = mild present; 2 = moderately present; 3 = severely present; and 4 = very severely present). Higher scores indicated worse outcome.

4. Worst Visual Analog Scale (VAS) [At Baseline, Weeks 2, 4, and 8]

   At study visits, participants recorded a mark for pruritus severity on a 10-cm horizontal line. This thermometer-type scale was marked with ratings of "no itch" (0 cm) and worst imaginable itch" (10 cm). Worst VAS (worst itch over the past 24 hours) was recorded. Higher scores indicated worse outcome.

5. Number of Participants With Improvement in Pruritus as Reported on Patient Global Assessment (PGA) [At Weeks 2, 4, and 8]

   The PGA included a question: Did the pruritus improve during the treatment period (yes/no).

6. Numeric Rating Scale (NRS) [At Baseline, Weeks 2, 4, and 8]

   Numeric Rating Scale: Using the patient diary, participants rated the following using an 11-point NRS (0 = no itching; to 10 = worst itch imaginable): average itching over the past 24 hours (Average NRS). Higher scores indicated worse outcome.

7. Dermatology Life Quality Index (DLQI) [At Baseline, Weeks 2, 4, and 8]

   At each visit, participants completed a DLQI questionnaire. The DLQI is a validated questionnaire consisting of 10 questions relating to the degree to which the participant's skin condition affected his/her daily activities. The DLQI questionnaire is designed for use in adults, i.e. participants over the age of 16. The scoring of each question is as follows: Very much: scored 3, A lot: scored 2, A little: scored 1, Not at all: scored 0, Not relevant: scored 0, Question 7, 'prevented work or studying': scored 3. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. Interpreting the DLQI Scores: 0 - 1: no effect at all on participant's life, 2 - 5: small effect on participant's life, 6 - 10: moderate effect on participant's life, 11 - 20: very large effect on participant's life, 21 - 30: extremely large effect on participant's life.

8. Pruritus-specific Quality of Life (ItchyQoL) [At Baseline, Weeks 2, 4, and 8]

   At each visit, participants completed an ItchyQoL questionnaire. The ItchyQoL is a validated questionnaire consisting of 22 questions based on the concerns and issues pertinent to participants with pruritus. Items should be scored for the following answers: Never: 1, Rarely: 2, Sometimes: 3, Often: 4, All the time:5. Higher scores indicated worse outcome. Total Score is obtained by calculating the unweighted mean of all ItchyQoL questions.

9. Patient Benefit Index, Version for Patients With Pruritus (PBI-P) [At Week 8 / End of Treatment]

   At Visits 2 and 5 (or Early termination) only, participants completed the standardized and validated PBI-P questionnaire. Prior to treatment, the first page of the questionnaire, the Patient Needs Questionnaire (PNQ), was administered to determine how different benefits of therapy were relevant for the individual participant. After treatment, using the Patient Benefit Questionnaire (PBQ), participants were asked to evaluate the extent to which the benefits they indicated were important to them were, in fact, realized. From all the items taken together, a weighted total benefit value was calculated, which represented the patient relevant therapy benefits. The mean score greater than 1 is considered to represent a clinically relevant improvement. The items are rated on a 5-point scale with values from 0 (not at all) to 4 (very), allowing for "does/did not apply to me" = 5; and missing value = -9. Higher scores indicated better outcome.

10. Number of Participants With Improvement in PN Lesions as Reported on Investigator Global Assessment (IGA) [At Week 8]

    Using the IGA, physicians rated change in PN lesions (if any) from +5 ("markedly improved") to -5 ("markedly worse"). Higher scores indicated better outcome.

11. Number of Participants With Improvement on Prurigo Activity Score (PAS) [At Day 1 and Week 8]

    Using the PAS, physicians described, localized, counted, and measured PN lesions. One of the 7 items was: Activity Stage (Stage 0-4: 0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, 4 = > 75%) a. Prurigo lesions with excoriations/crusts Participants with PAS activity stage (prurigo lesions with excoriations/crusts) is presented in the below table.

12. Participants With Rescue Medication Usage [Pre-treatment, upto 8 Weeks]

    Rescue medications included cetirizine hydrochloride, desloratadine, levocetirizine, and loratadine.

13. Number of Participants With Adverse Events (AEs) [From the time of informed consent (Screening) until the last study visit (follow-up phone call, Week 10)]

    An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE (also referred to as an adverse experience) could be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, without any judgment about causality.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects meeting all of the following criteria will be eligible for study entry:

1. Males or females who are at least 18 years and no more than 80 years of age at Screening.

2. Must have PN (defined as the presence of pruritic nodules due to chronic pruritus,) of more than 6 weeks duration despite treatment with current therapies such as antihistamines or corticosteroids ("treatment resistant" PN).

3. Must have PN lesions on both arms, both legs, and/or the trunk (ie, the lesions must not be localized).

4. Must have a VAS pruritus score of 70 or greater within 72 hours of Baseline.

5. Males, non-fecund females (ie, surgically sterilized, if procedure was done 12 months before screening or subject is postmenopausal, without menses for 12 months before screening), or females of childbearing potential using an acceptable method of birth control for a period of 35 days before the first dosing, and all females must have a negative pregnancy test at the screening and baseline visits:

Note 1: Acceptable methods of birth control include any one of the following:

abstinence, vasectomized sexual partner, hormonal methods (ie, birth-control pill, hormonal IUD, Depo-Provera, implants, patch, intravaginal device [NuvaRing]), intrauterine device (IUD [copper banded coils]), diaphragm, cervical cap, or condom with spermicidal jelly or foam. Subjects using oral contraceptives must also use a reliable backup method of birth control during the study and until the first menses after the last dose of study medication or for 14 days menses after the last dose of study medication.

1. Willing and able to understand and provide written informed consent.

2. Willing and able to comply with study requirements and restrictions including the discontinuation of all current therapies for pruritus.

3. Subjects must be in good health as determined by medical history, physical examination, and results of Electro Cardio Gram (ECG) and clinical laboratory tests (including urinalysis).

4. Agreeing to confidential use and storage of all data and use of all anonymized data for publication including scientific publication.

Exclusion Criteria:

• Subjects not eligible for the study are those who:

• Have chronic pruritus due conditions other than PN, such as the following conditions:

• Lichen simplex chronicus

• Lichen amyloidosus

• Localized pruritus (e.g., only one arm affected)

• Neuropathic and psychogenic pruritus (notalgia paresthetica, brachioradial pruritus, somatoform prurigo, dilusional parasitosis, depression associated prurigo)

• Active dermatoses needing immediate therapy such as atopic dermatitis (without PN) or bullous pemphigoid;

• Have a history of use (within the specified time periods) of the medications listed below. Prior to randomization, a subject who used any of these medications must undergo a washout period equal to the length of the interval specified below (eg, 2 weeks for antihistamines, 4 weeks for naltrexone, and 4 weeks for cyclosporine A).

• Topical or systemic antihistamines, (used ≤2 weeks prior to the baseline visit) [loratindine, or cetirizine may act as rescue medication during treatment];

• Topical calcineurin inhibitors, topical capsaicin, menthol, camphor, polidocanol, topical antibiotics, antiseptic baths and cleansing lotions (used ≤2 weeks prior to the baseline visit);

• Topical steroids (used ≤2 weeks prior to the baseline visit);

• Naltrexone, paroxetine, fluvoxamine, amitriptyline, gabapentin, pregabalin, or UVtherapy (prescribed for the pruritus treatment) (used ≤4 weeks prior to the baseline visit);

• Systemic steroids (used ≤4 weeks prior to the baseline visit);

• Cyclosporine A and other immunosuppressants (used ≤4 weeks prior to the baseline visit).

• Have any medical condition or disability that would interfere with the assessment of safety or efficacy in this trial or would compromise the ability of the subject to undergo study procedures or to give informed consent.

• Have any chronic or acute medical condition that, in the opinion of the investigator, might interfere with the study results or place the subject at undue risk.

• Have a history of sensitivity to any components of the study material.

• Are females of childbearing potential who are unwilling to use adequate contraception or who are breast feeding.

• Have chronic renal disease, ie, serum creatinine greater than 2.4 mg/dL.

• Have aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2 times the upper limit of normal. Subjects with hepatitis B or C who have normal liver function may be enrolled.

• Have a current malignancy (such as Hodgkin's lymphoma, B or T cell lymphoma, or myeloma) or blood cell dyscrasia (eg, polycythemia or myelofibrosis) that might lead to systemic chronic pruritus.

• Subjects with untreated hyperthyroidism.

• Have pruritus of psychiatric etiology (eg, delusions of parasitosis, obsessive compulsive disorder, or major depression) or neuropathic etiology (eg, due to shingles, spinal cord injury or with neurologic deficit).

• Have pruritus due to urticaria, drug allergy, or infection (such as pityriasis rosea or tinea or active human immunodeficiency virus [HIV]). Note: Subjects with HIV who have undetectable viral load, CD 4 counts >200 cells/cc, and stable retroviral therapy may enroll.

• Are on medications known to cause pruritus (ie, Erbitux®, opioids, cocaine, amphetamines, and angiotensin converting enzyme [ACE] inhibitors) and are suspected of having drug-induced pruritus.

• Have taken investigational medications within 30 days prior to Screening.

• Are currently participating in any other clinical study.

• Have a history (within the previous 4 weeks) of use of tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRIS), monoamine oxidase (MAO) inhibitors, opioids, immunemodulators (e.g. azathioprine, methotrexate, mycophenolate mofetil, cyclosporine A, antibodies), or neuroactive medications (e.g. pregabalin, gabapentin).

• Have a history (within the previous 4 weeks) of use of sedatives or tranquilizers.

Subjects must undergo an appropriate washout period from any sedatives or tranquilizers before enrolling in the study.

• Are currently treated with strong CYP3A4 inhibitors (e.g. conazole, ketoconazole, fluconazole, itraconazole, voroconazole etc. or erythromycin). The co-administration of moderate CYP3A4 inhibitors to VPD-737 may be allowed with investigator agreement and appropriate safety monitoring.

• Received ultraviolet B (UVB) or psoralen + ultraviolet A (PUVA) treatment within 30 days prior to Screening.

• Within the past 12 months, have expressed suicidal ideation with some intent to act.

• Started or changed creams, or emollients including over-the-counter (OTC) preparations or bath oil treatment for relief of pruritus within 2 weeks prior to Screening.

• Have any social or medical condition (eg, alcoholism, drug dependency, psychotic state) that, in the investigator's opinion, might interfere with the subject's ability to comply with the requirements of the protocol.

• Are employees of the study site or of the Sponsor's company.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Study Site 07	Berlin-Mitte		Germany	10117
2	Study Site 08	Bonn		Germany	53127
3	Study Site 06	Dresden		Germany	01307
4	Study Site 12	Dusseldorf		Germany	40225
5	Study Site 02	Frankfurt		Germany	60590
6	Study Site 09	Hamburg		Germany	20246
7	Study Site 05	Heidelberg		Germany	69120
8	Study Site 03	Kiel		Germany	24105
9	Study Site 11	Leipzig		Germany	04103
10	Study Site 04	Lubeck		Germany	23538
11	Study Site 14	Mainz		Germany	55101
12	Study Site 01	Muenster		Germany	48149
13	Study Site 16	München		Germany	80337
14	Study Site 15	Selters		Germany	56242
15	Study Site 10	Tübingen		Germany	72076

Sponsors and Collaborators

• Vyne Therapeutics Inc.

Investigators

• Principal Investigator: Sonja Staender, MD, University of Muenster, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Vyne Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT02196324
• Other Study ID Numbers: TCP-102
• First Posted: Jul 22, 2014
• Last Update Posted: May 20, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Vyne Therapeutics Inc.: Prurigo Nodularis; Atopic Dermatitis; Lichen-simplex chronicus
• Additional relevant MeSH terms: Prurigo; Neurodermatitis; Serlopitant

Study Results

Participant Flow

Recruitment Details	The participants were randomized at 15 sites in Germany.
Pre-assignment Detail	This study consisted of a screening period of up to 4 weeks. All the assessments were done at screening as per the schedule of assessment.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Period Title: Overall Study
STARTED	63	65
COMPLETED	48	57
NOT COMPLETED	15	8

Baseline Characteristics

Arm/Group Title	Placebo	Serlopitant	Total
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Total of all reporting groups
Overall Participants	63	64	127
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.1 (11.14)	57.1 (12.00)	57.6 (11.54)
Sex: Female, Male (Count of Participants)
Female	36 57.1%	31 48.4%	67 52.8%
Male	27 42.9%	33 51.6%	60 47.2%

Outcome Measures

1. Primary Outcome

Title	Average Visual Analog Scale at Baseline
Description	At study visits, participants recorded a mark for pruritus severity on a 10-cm horizontal line. This thermometer-type scale was marked with ratings of "no itch" (0 cm) and worst imaginable itch" (10 cm). Average Visual Analog Scale (VAS) (average itch over the past 24 hours) was recorded. Higher scores indicated worse outcome.
Time Frame	At Baseline

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	63	64
Mean (Standard Deviation) [Units on a scale]	7.92 (1.630)	7.88 (1.311)

2. Primary Outcome

Title	Average Visual Analog Scale at Week 2
Description	At study visits, participants recorded a mark for pruritus severity on a 10-cm horizontal line. This thermometer-type scale was marked with ratings of "no itch" (0 cm) and worst imaginable itch" (10 cm). Average VAS (average itch over the past 24 hours) was recorded. Higher scores indicated worse outcome.
Time Frame	At Week 2

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	61	63
Mean (Standard Deviation) [Units on a scale]	7.01 (2.187)	6.06 (2.236)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.0111
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.5 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

3. Primary Outcome

Title	Average Visual Analog Scale at Week 4
Description	At study visits, participants recorded a mark for pruritus severity on a 10-cm horizontal line. This thermometer-type scale was marked with ratings of "no itch" (0 cm) and worst imaginable itch" (10 cm). Average VAS (average itch over the past 24 hours) was recorded. Higher scores indicated worse outcome.
Time Frame	At Week 4

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	54	64
Mean (Standard Deviation) [Units on a scale]	6.32 (2.403)	5.41 (2.719)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.0248
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.8 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.43
	Estimation Comments

4. Primary Outcome

Title	Average Visual Analog Scale at Week 8
Description	At study visits, participants recorded a mark for pruritus severity on a 10-cm horizontal line. This thermometer-type scale was marked with ratings of "no itch" (0 cm) and worst imaginable itch" (10 cm). Average VAS (average itch over the past 24 hours) was recorded. Higher scores indicated worse outcome.
Time Frame	At Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	46	57
Mean (Standard Deviation) [Units on a scale]	5.56 (2.630)	4.21 (2.746)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -2.6 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.47
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Improvement in Pruritus as Reported on Verbal Rating Scale (VRS) - Pruritus
Description	At study visits, participants used the VRS to rate their skin sensations (pruritus, burning, and stinging) using a 5-point scale (0 = not present; 1 = mild present; 2 = moderately present; 3 = severely present; and 4 = very severely present). Higher scores indicated worse outcome.
Time Frame	At Baseline and Week 8

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, number analyzed in each row signifies only the participants with available data that were analyzed for each parameter.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	63	64
Baseline, Mild Present	2 3.2%	0 0%
Baseline, Moderately Present	18 28.6%	17 26.6%
Baseline, Severely Present	20 31.7%	32 50%
Baseline, Very Severely Present	22 34.9%	15 23.4%
Week 8, Not Present	2 3.2%	4 6.3%
Week 8, Mild Present	11 17.5%	27 42.2%
Week 8, Moderately Present	18 28.6%	17 26.6%
Week 8, Severely Present	9 14.3%	7 10.9%
Week 8, Very Severely Present	5 7.9%	2 3.1%

6. Secondary Outcome

Title	Number of Participants With Improvement in Burning as Reported on Verbal Rating Scale (VRS) - Burning
Description	At study visits, participants used the VRS to rate their skin sensations (pruritus, burning, and stinging) using a 5-point scale (0 = not present; 1 = mild present; 2 = moderately present; 3 = severely present; and 4 = very severely present). Higher scores indicated worse outcome.
Time Frame	At Baseline and Week 8

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, number analyzed in each row signifies only the participants with available data that were analyzed for each parameter.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	63	64
Baseline, Not Present	14 22.2%	21 32.8%
Baseline, Mild Present	8 12.7%	5 7.8%
Baseline, Moderately Present	13 20.6%	21 32.8%
Baseline, Severely Present	18 28.6%	12 18.8%
Baseline, Very Severely Present	9 14.3%	5 7.8%
Week 8, Not Present	11 17.5%	31 48.4%
Week 8, Mild Present	9 14.3%	10 15.6%
Week 8, Moderately Present	15 23.8%	8 12.5%
Week 8, Severely Present	5 7.9%	6 9.4%
Week 8, Very Severely Present	3 4.8%	1 1.6%

7. Secondary Outcome

Title	Number of Participants With Improvement in Stinging as Reported on Verbal Rating Scale (VRS) - Stinging
Description	At study visits, participants used the VRS to rate their skin sensations (pruritus, burning, and stinging) using a 5-point scale (0 = not present; 1 = mild present; 2 = moderately present; 3 = severely present; and 4 = very severely present). Higher scores indicated worse outcome.
Time Frame	At Baseline and Week 8

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, number analyzed in each row signifies only the participants with available data that were analyzed for each parameter.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	63	64
Baseline, Not Present	26 41.3%	21 32.8%
Baseline, Mild Present	8 12.7%	14 21.9%
Baseline, Moderately Present	11 17.5%	16 25%
Baseline, Severely Present	9 14.3%	10 15.6%
Baseline, Very Severely Present	8 12.7%	3 4.7%
Week 8, Not Present	18 28.6%	30 46.9%
Week 8, Mild Present	8 12.7%	12 18.8%
Week 8, Moderately Present	10 15.9%	7 10.9%
Week 8, Severely Present	4 6.3%	4 6.3%
Week 8, Very Severely Present	3 4.8%	1 1.6%

8. Secondary Outcome

Title	Worst Visual Analog Scale (VAS)
Description	At study visits, participants recorded a mark for pruritus severity on a 10-cm horizontal line. This thermometer-type scale was marked with ratings of "no itch" (0 cm) and worst imaginable itch" (10 cm). Worst VAS (worst itch over the past 24 hours) was recorded. Higher scores indicated worse outcome.
Time Frame	At Baseline, Weeks 2, 4, and 8

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, number analyzed in each row signifies only the participants with available data that were analyzed for each parameter.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	63	64
Baseline	8.75 (1.316)	8.43 (1.190)
Week 2	7.92 (1.733)	6.85 (2.157)
Week 4	7.46 (2.285)	6.19 (2.690)
Week 8	6.73 (2.591)	4.82 (2.729)

9. Secondary Outcome

Title	Number of Participants With Improvement in Pruritus as Reported on Patient Global Assessment (PGA)
Description	The PGA included a question: Did the pruritus improve during the treatment period (yes/no).
Time Frame	At Weeks 2, 4, and 8

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, number analyzed in each row signifies only the participants with available data that were analyzed for each parameter.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	63	64
Week 2	23 36.5%	37 57.8%
Week 4	29 46%	43 67.2%
Week 8	25 39.7%	47 73.4%

10. Secondary Outcome

Title	Numeric Rating Scale (NRS)
Description	Numeric Rating Scale: Using the patient diary, participants rated the following using an 11-point NRS (0 = no itching; to 10 = worst itch imaginable): average itching over the past 24 hours (Average NRS). Higher scores indicated worse outcome.
Time Frame	At Baseline, Weeks 2, 4, and 8

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	63	64
Baseline	7.65 (1.669)	7.60 (1.455)
Week 2	6.23 (2.043)	5.50 (1.944)
Week 4	5.80 (2.133)	4.91 (2.158)
Week 8	5.11 (2.320)	4.02 (2.190)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments	Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.4 to -0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments	Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.7 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments	Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0175
	Comments	p-value assume equal variance
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -2.0 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Dermatology Life Quality Index (DLQI)
Description	At each visit, participants completed a DLQI questionnaire. The DLQI is a validated questionnaire consisting of 10 questions relating to the degree to which the participant's skin condition affected his/her daily activities. The DLQI questionnaire is designed for use in adults, i.e. participants over the age of 16. The scoring of each question is as follows: Very much: scored 3, A lot: scored 2, A little: scored 1, Not at all: scored 0, Not relevant: scored 0, Question 7, 'prevented work or studying': scored 3. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. Interpreting the DLQI Scores: 0 - 1: no effect at all on participant's life, 2 - 5: small effect on participant's life, 6 - 10: moderate effect on participant's life, 11 - 20: very large effect on participant's life, 21 - 30: extremely large effect on participant's life.
Time Frame	At Baseline, Weeks 2, 4, and 8

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, number analyzed in each row signifies only the participants with available data that were analyzed for each parameter.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	63	64
Baseline	14.9 (7.03)	13.7 (6.76)
Week 2	12.4 (6.94)	11.6 (6.20)
Week 4	11.6 (6.56)	11.4 (6.80)
Week 8	11.3 (6.83)	10.6 (7.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments	Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -3.1 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments	Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -2.7 to 2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments	Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -3.6 to 2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Pruritus-specific Quality of Life (ItchyQoL)
Description	At each visit, participants completed an ItchyQoL questionnaire. The ItchyQoL is a validated questionnaire consisting of 22 questions based on the concerns and issues pertinent to participants with pruritus. Items should be scored for the following answers: Never: 1, Rarely: 2, Sometimes: 3, Often: 4, All the time:5. Higher scores indicated worse outcome. Total Score is obtained by calculating the unweighted mean of all ItchyQoL questions.
Time Frame	At Baseline, Weeks 2, 4, and 8

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, number analyzed in each row signifies only the participants with available data that were analyzed for each parameter.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	63	64
Baseline	3.68 (0.737)	3.52 (0.679)
Week 2	3.50 (0.795)	3.36 (0.670)
Week 4	3.36 (0.863)	3.26 (0.730)
Week 8	3.33 (0.876)	3.09 (0.904)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments	Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments	Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments	Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Patient Benefit Index, Version for Patients With Pruritus (PBI-P)
Description	At Visits 2 and 5 (or Early termination) only, participants completed the standardized and validated PBI-P questionnaire. Prior to treatment, the first page of the questionnaire, the Patient Needs Questionnaire (PNQ), was administered to determine how different benefits of therapy were relevant for the individual participant. After treatment, using the Patient Benefit Questionnaire (PBQ), participants were asked to evaluate the extent to which the benefits they indicated were important to them were, in fact, realized. From all the items taken together, a weighted total benefit value was calculated, which represented the patient relevant therapy benefits. The mean score greater than 1 is considered to represent a clinically relevant improvement. The items are rated on a 5-point scale with values from 0 (not at all) to 4 (very), allowing for "does/did not apply to me" = 5; and missing value = -9. Higher scores indicated better outcome.
Time Frame	At Week 8 / End of Treatment

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	61	63
Mean (Standard Deviation) [Units on a scale]	0.81 (0.984)	1.16 (1.095)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0625
	Comments	p-value assume equal variance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Number of Participants With Improvement in PN Lesions as Reported on Investigator Global Assessment (IGA)
Description	Using the IGA, physicians rated change in PN lesions (if any) from +5 ("markedly improved") to -5 ("markedly worse"). Higher scores indicated better outcome.
Time Frame	At Week 8

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	47	57
Markedly Improved	0 0%	4 6.3%
Largely Improved	2 3.2%	3 4.7%
Moderately To Largely Improved	4 6.3%	3 4.7%
Moderately Improved	4 6.3%	11 17.2%
Mildly Improved	9 14.3%	17 26.6%
Baseline	14 22.2%	7 10.9%
Mildly Worse	8 12.7%	5 7.8%
Moderately Worse	4 6.3%	4 6.3%
Moderately To Largely Worse	1 1.6%	1 1.6%
Largely Worse	1 1.6%	2 3.1%

15. Secondary Outcome

Title	Number of Participants With Improvement on Prurigo Activity Score (PAS)
Description	Using the PAS, physicians described, localized, counted, and measured PN lesions. One of the 7 items was: Activity Stage (Stage 0-4: 0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, 4 = > 75%) a. Prurigo lesions with excoriations/crusts Participants with PAS activity stage (prurigo lesions with excoriations/crusts) is presented in the below table.
Time Frame	At Day 1 and Week 8

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized. Here, number analyzed in each row signifies only the participants with available data that were analyzed for each day and week.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	63	64
Day 1, 1 - 25 %	7 11.1%	5 7.8%
Day 1, 26 - 50 %	18 28.6%	19 29.7%
Day 1, 51 - 75 %	17 27%	19 29.7%
Day 1, >75 %	21 33.3%	21 32.8%
Week 8, 0 %	0 0%	4 6.3%
Week 8, 1 - 25 %	11 17.5%	15 23.4%
Week 8, 26 - 50 %	12 19%	12 18.8%
Week 8, 51 - 75 %	11 17.5%	11 17.2%
Week 8, >75 %	13 20.6%	15 23.4%

16. Secondary Outcome

Title	Participants With Rescue Medication Usage
Description	Rescue medications included cetirizine hydrochloride, desloratadine, levocetirizine, and loratadine.
Time Frame	Pre-treatment, upto 8 Weeks

Outcome Measure Data

Analysis Population Description

The ITT population - all randomized participants who were treated. This population was analyzed based upon the treatment to which participants were randomized.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	63	64
Pre-treatment Rescue Medication Used	15 23.8%	17 26.6%
Used Rescue Medication	12 19%	8 12.5%

17. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE (also referred to as an adverse experience) could be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, without any judgment about causality.
Time Frame	From the time of informed consent (Screening) until the last study visit (follow-up phone call, Week 10)

Outcome Measure Data

Analysis Population Description

Safety population - participants who received at least one dose of study drug. This population was analyzed based upon the actual treatment received. Participants with dosing errors were assigned to a treatment group based upon the treatment they received most often.

Arm/Group Title	Placebo	Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.	Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
Measure Participants	63	64
Participants with AEs	39 61.9%	46 71.9%
Participants with Treatment-emergent adverse events (TEAEs)	39 61.9%	46 71.9%
Participants with TEAEs leading to discontinuation	6 9.5%	3 4.7%
Participants with TEAEs related to study drug	22 34.9%	31 48.4%
Participants with TEAEs by maximum severity, Mild	14 22.2%	18 28.1%
Participants with TEAEs by maximum severity, Moderate	22 34.9%	22 34.4%
Participants with TEAEs by maximum severity, Severe	3 4.8%	6 9.4%
Participants with serious TEAEs	2 3.2%	3 4.7%

Adverse Events

Time Frame	From the time of informed consent (Screening) until the last study visit (follow-up phone call, Week 10).
Arm/Group Title	Placebo		Serlopitant
Arm/Group Description	Randomized participants took matching placebo tablets for oral administration as 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.		Randomized participants took Serlopitant 5 mg tablets for oral administration at a loading dose of 3 tablets at baseline (Day 1) followed by 1 tablet every day at bedtime for 8 weeks.
All Cause Mortality
	Placebo		Serlopitant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/63 (0%)		0/64 (0%)
Serious Adverse Events
	Placebo		Serlopitant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/63 (3.2%)		3/64 (4.7%)
Cardiac disorders
Bradycardia	1/63 (1.6%)		0/64 (0%)
Ear and labyrinth disorders
Vertigo	0/63 (0%)		1/64 (1.6%)
Nervous system disorders
Dizziness	0/63 (0%)		1/64 (1.6%)
Syncope	1/63 (1.6%)		0/64 (0%)
Psychiatric disorders
Depression	0/63 (0%)		1/64 (1.6%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/63 (1.6%)		0/64 (0%)
Skin and subcutaneous tissue disorders
Actinic elastosis	0/63 (0%)		1/64 (1.6%)
Neurodermatitis	1/63 (1.6%)		0/64 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Serlopitant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/63 (31.7%)		31/64 (48.4%)
Gastrointestinal disorders
Diarrhoea	3/63 (4.8%)		7/64 (10.9%)
General disorders
Fatigue	4/63 (6.3%)		6/64 (9.4%)
Oedema peripheral	0/63 (0%)		4/64 (6.3%)
Infections and infestations
Nasopharyngitis	2/63 (3.2%)		11/64 (17.2%)
Urinary tract infection	4/63 (6.3%)		0/64 (0%)
Nervous system disorders
Dizziness	1/63 (1.6%)		4/64 (6.3%)
Headache	4/63 (6.3%)		4/64 (6.3%)
Skin and subcutaneous tissue disorders
Pruritus	7/63 (11.1%)		3/64 (4.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.