Trial Outcomes & Findings for Study of the Efficacy, Safety and Tolerability of Serlopitant for the Treatment of Pruritus (Itch) With Prurigo Nodularis (NCT NCT03546816)

NCT ID: NCT03546816

Last Updated: 2021-05-20

Results Overview

During the study, Worst Itch Numeric Rating Scale (WI-NRS) assessments were reported by the subject via eDiary once daily from screening/mid-screening visit through the follow-up visit. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. Subjects were considered responders if they had at least a 4-point reduction from baseline in weekly average WI-NRS at Week 10.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 285 participants
• Primary outcome timeframe: At Week 10
• Results posted on: 2021-05-20

Participant Flow

The study was conducted at 49 sites in United States from 02 May 2018 to 14 February 2020. All subjects who met the study entry criteria were randomized in a 1:1 ratio to receive once-daily oral doses of serlopitant 5 mg or placebo for 10 weeks.

During the screening period (2-4 weeks), all subjects were evaluated for eligibility and assessed for conditions associated with chronic pruritus. Subjects were to complete an electronic diary (eDiary) during screening visit.

Participant milestones

Measure	Serlopitant 5 mg Randomized subjects received serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Overall Study STARTED	142	143
Overall Study COMPLETED	121	124
Overall Study NOT COMPLETED	21	19

Reasons for withdrawal

Measure	Serlopitant 5 mg Randomized subjects received serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Overall Study Adverse Event	5	3
Overall Study Lack of Efficacy	2	4
Overall Study Pregnancy	1	0
Overall Study Physician Decision	2	0
Overall Study Withdrawal by Subject	8	10
Overall Study Lost to Follow-up	3	2

Baseline Characteristics

Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/treatment emergent adverse event (TEAE).

Baseline characteristics by cohort

Measure	Serlopitant 5 mg n=142 Participants Randomized subjects received serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=143 Participants Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Total n=285 Participants Total of all reporting groups
Age, Continuous	58.7 Years STANDARD_DEVIATION 13.54 • n=139 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/treatment emergent adverse event (TEAE).	56.0 Years STANDARD_DEVIATION 12.99 • n=141 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/treatment emergent adverse event (TEAE).	57.4 Years STANDARD_DEVIATION 13.30 • n=280 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/treatment emergent adverse event (TEAE).
Sex: Female, Male Female	92 Participants n=139 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	89 Participants n=141 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	181 Participants n=280 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.
Sex: Female, Male Male	47 Participants n=139 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	52 Participants n=141 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	99 Participants n=280 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=139 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	0 Participants n=141 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	1 Participants n=280 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.
Race (NIH/OMB) Asian	6 Participants n=139 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	11 Participants n=141 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	17 Participants n=280 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=139 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	1 Participants n=141 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	1 Participants n=280 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.
Race (NIH/OMB) Black or African American	27 Participants n=139 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	33 Participants n=141 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	60 Participants n=280 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.
Race (NIH/OMB) White	102 Participants n=139 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	91 Participants n=141 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	193 Participants n=280 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.
Race (NIH/OMB) More than one race	3 Participants n=139 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	5 Participants n=141 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	8 Participants n=280 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=139 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	0 Participants n=141 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.	0 Participants n=280 Participants • Three subjects were excluded in the serlopitant 5 mg arm and 2 subjects were excluded in the placebo arm due to no evidence of subject dosing and/or no post-Baseline assessment/TEAE.

PRIMARY outcome

Timeframe: At Week 10

Population: Intent-to-Treat Population: included all randomized subjects who were dispensed study drug.

During the study, Worst Itch Numeric Rating Scale (WI-NRS) assessments were reported by the subject via eDiary once daily from screening/mid-screening visit through the follow-up visit. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. Subjects were considered responders if they had at least a 4-point reduction from baseline in weekly average WI-NRS at Week 10.

Outcome measures

Measure	Serlopitant 5 mg n=142 Participants Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=142 Participants Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Percent of Subjects With Worst-Itch Numeric Rating Scale 4-point Responder at Week 10	26.45 Percentage of subjects	20.31 Percentage of subjects

SECONDARY outcome

Timeframe: At Week 4

Population: Intent-to-Treat Population: included all randomized subjects who were dispensed study drug.

During the study, WI-NRS assessments were reported by the subject via eDiary once daily from screening/mid-screening visit through the follow-up visit. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity.

Outcome measures

Measure	Serlopitant 5 mg n=142 Participants Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=142 Participants Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Percent of Subjects With WI-NRS 4-point Responder at Week 4	17.66 Percentage of subjects	7.80 Percentage of subjects

SECONDARY outcome

Timeframe: At Week 2

Population: Intent-to-Treat Population: included all randomized subjects who were dispensed study drug.

During the study, WI-NRS assessments were reported by the subject via eDiary once daily from screening/mid-screening visit through the follow-up visit. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity.

Outcome measures

Measure	Serlopitant 5 mg n=142 Participants Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=142 Participants Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Percent of Subjects With WI-NRS 4-point Responder at Week 2	8.45 Percentage of subjects	4.93 Percentage of subjects

SECONDARY outcome

Timeframe: At Weeks 2, 4, 6, and 10

Population: Intent-to-Treat Population: included all randomized subjects who were dispensed study drug.

During the study, WI-NRS assessments were reported by the subject via eDiary once daily from screening/mid-screening visit through the follow-up visit. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity.

Outcome measures

Measure	Serlopitant 5 mg n=142 Participants Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=142 Participants Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Change From Baseline in WI-NRS at Weeks 2, 4, 6, and 10 Change from Baseline at Week 4	-1.82 Score on a scale Standard Deviation 2.226	-1.32 Score on a scale Standard Deviation 2.248
Change From Baseline in WI-NRS at Weeks 2, 4, 6, and 10 Change from Baseline at Week 2	-1.30 Score on a scale Standard Deviation 1.725	-0.96 Score on a scale Standard Deviation 1.740
Change From Baseline in WI-NRS at Weeks 2, 4, 6, and 10 Change from Baseline at Week 6	-2.13 Score on a scale Standard Deviation 2.436	-1.65 Score on a scale Standard Deviation 2.460
Change From Baseline in WI-NRS at Weeks 2, 4, 6, and 10 Change from Baseline at Week 10	-2.47 Score on a scale Standard Deviation 2.633	-2.06 Score on a scale Standard Deviation 2.612

SECONDARY outcome

Timeframe: At Weeks 2, 4, and 10

Population: Intent-to-Treat Population: included all randomized subjects who were dispensed study drug.

During the study, WI-NRS assessments were reported by the subject via eDiary once daily from screening/mid-screening visit through the follow-up visit. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. For the 3-point responder rate, subjects were considered responders if they had at least a 3-point reduction between baseline and the corresponding week.

Outcome measures

Measure	Serlopitant 5 mg n=142 Participants Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=142 Participants Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Percent of Subjects With WI-NRS 3-point Responder at Weeks 2, 4, and 10 Percentage of responders at Week 2	14.79 Percentage of subjects	9.27 Percentage of subjects
Percent of Subjects With WI-NRS 3-point Responder at Weeks 2, 4, and 10 Percentage of responders at Week 4	23.32 Percentage of subjects	14.31 Percentage of subjects
Percent of Subjects With WI-NRS 3-point Responder at Weeks 2, 4, and 10 Percentage of responders at Week 10	35.58 Percentage of subjects	27.83 Percentage of subjects

SECONDARY outcome

Timeframe: At Weeks 2, 4, and 10

Population: Intent-to-Treat Population: included all randomized subjects who were dispensed study drug.

The IGA PN-A is an instrument used to assess the overall activity of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 (clear) to 4 (severe). Higher scores indicate severe prurigo nodularis.

Outcome measures

Measure	Serlopitant 5 mg n=142 Participants Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=142 Participants Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Change From Baseline in Investigator's Global Assessment of Prurigo Nodularis Activity (IGA PN-A) to Weeks 2, 4, and 10 Change from Baseline at Week 2	-0.3 Score on a scale Standard Deviation 0.71	-0.3 Score on a scale Standard Deviation 0.71
Change From Baseline in Investigator's Global Assessment of Prurigo Nodularis Activity (IGA PN-A) to Weeks 2, 4, and 10 Change from Baseline at Week 4	-0.6 Score on a scale Standard Deviation 0.81	-0.4 Score on a scale Standard Deviation 0.81
Change From Baseline in Investigator's Global Assessment of Prurigo Nodularis Activity (IGA PN-A) to Weeks 2, 4, and 10 Change from Baseline at Week 10	-0.7 Score on a scale Standard Deviation 0.99	-0.6 Score on a scale Standard Deviation 0.99

SECONDARY outcome

Timeframe: At Weeks 2, 4, and 10

Population: Intent-to-Treat Population: included all randomized subjects who were dispensed study drug.

The IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 (clear) to 4 (severe). Higher scores indicate severe prurigo nodularis.

Outcome measures

Measure	Serlopitant 5 mg n=142 Participants Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=142 Participants Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Change From Baseline in Investigator's Global Assessment of PN Stage (IGA PN-S) to Weeks 2, 4, and 10 Change from Baseline to Week 2	-0.2 Score on a scale Standard Deviation 0.52	-0.1 Score on a scale Standard Deviation 0.52
Change From Baseline in Investigator's Global Assessment of PN Stage (IGA PN-S) to Weeks 2, 4, and 10 Change from Baseline to Week 4	-0.4 Score on a scale Standard Deviation 0.71	-0.3 Score on a scale Standard Deviation 0.71
Change From Baseline in Investigator's Global Assessment of PN Stage (IGA PN-S) to Weeks 2, 4, and 10 Change from Baseline to Week 10	-0.5 Score on a scale Standard Deviation 0.86	-0.4 Score on a scale Standard Deviation 0.86

SECONDARY outcome

Timeframe: At Week 10

Population: Intent-to-Treat Population: included all randomized subjects who were dispensed study drug.

Dermatology Life Quality Index (DLQI) is a dermatology specific quality of life (QoL) instrument designed to assess the impact of the skin disease on a subject's QoL over the prior week. It is a ten item questionnaire that assesses overall QoL and six aspects that may affect QoL (symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment). The DLQI questions are rated by the subject as 0 (not at all) to 3 (very much). Scores range from 0 to 30 with higher scores indicating poor QoL.

Outcome measures

Measure	Serlopitant 5 mg n=142 Participants Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=142 Participants Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 10	-4.1 Score on a scale Standard Deviation 5.20	-4.3 Score on a scale Standard Deviation 5.21

SECONDARY outcome

Timeframe: At Week 10

Population: Intent-to-Treat Population: included all randomized subjects who were dispensed study drug.

DLQI is a dermatology specific QoL instrument designed to assess the impact of the skin disease on a subject's QoL over the prior week. It is a ten item questionnaire that assesses overall QoL and six aspects that may affect QoL (symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment) The DLQI question 1 is to measure how itchy, sore, painful or stinging the subject's skin had been. It is rated by the subject as 0 (not at all) to 3 (very much). Scores range from 0 to 30 with higher scores indicating poor QoL.

Outcome measures

Measure	Serlopitant 5 mg n=142 Participants Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=142 Participants Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Change From Baseline in DLQI Question 1 to Week 10	-0.8 Score on a scale Standard Deviation 0.80	-0.6 Score on a scale Standard Deviation 0.81

SECONDARY outcome

Timeframe: 35 days (+3 days) after Week 10 or Early Treatment Discontinuation

Population: Safety population: included all treated subjects with at least one post-baseline assessment or a reported TEAE.

Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.

Outcome measures

Measure	Serlopitant 5 mg n=139 Participants Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=141 Participants Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events (SAEs) Subjects with any TEAE	74 Participants	64 Participants
Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events (SAEs) Subjects with any Related TEAE	20 Participants	9 Participants
Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events (SAEs) Subjects with any Serious TEAE	6 Participants	3 Participants
Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events (SAEs) Subjects with any Related Serious TEAE	0 Participants	0 Participants
Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events (SAEs) Subjects who Died	0 Participants	0 Participants
Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events (SAEs) Subjects who discontinued drug due to TEAE	5 Participants	3 Participants

Adverse Events

Serlopitant 5 mg

Serious events: 6 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Serlopitant 5 mg n=141 participants at risk；n=139 participants at risk Randomized subjects received serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=139 participants at risk；n=141 participants at risk Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.72% 1/139 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.	0.00% 0/141 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.72% 1/139 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.	0.00% 0/141 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.
Psychiatric disorders Schizoaffective disorder	0.72% 1/139 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.	0.00% 0/141 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.
Gastrointestinal disorders Haematochezia	0.72% 1/139 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.	0.00% 0/141 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.72% 1/139 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.	0.00% 0/141 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.
Infections and infestations Pneumonia	0.72% 1/139 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.	0.00% 0/141 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.
Vascular disorders Peripheral arterial occlusive disease	0.72% 1/139 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.	0.00% 0/141 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.00% 0/139 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.	0.71% 1/141 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.
Infections and infestations Abscess limb	0.00% 0/139 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.	0.71% 1/141 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.
Surgical and medical procedures Knee arthroplasty	0.00% 0/139 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.	0.71% 1/141 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.

Other adverse events

Measure	Serlopitant 5 mg n=141 participants at risk；n=139 participants at risk Randomized subjects received serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Placebo n=139 participants at risk；n=141 participants at risk Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Infections and infestations Upper respiratory tract infection	7.1% 10/141 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.	2.2% 3/139 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.
Skin and subcutaneous tissue disorders Pruritus	6.4% 9/141 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.	1.4% 2/139 • 35 days (+3 days) after Week 10 or Early Treatment Discontinuation Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected.

Additional Information

Iain Stuart, PhD

Menlo Therapeutics Inc.

Phone: 1- 800-775-7936

Email: Iain.Stuart@foamix.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60