Study of the Efficacy, Safety, and Tolerability of Serlop... | NCT03841331

Label	Type	Description	Intervention Names
5 mg Serlopitant Tablets	Experimental	Serlopitant Tablets	Drug: 5 mg Serlopitant Tablets
5 mg Placebo Tablets	Placebo Comparator	Placebo Tablets	Drug: Matching Placebo Tablets

Name	Type	Description	Arm Group Labels	Other Names
5 mg Serlopitant Tablets	Drug	Serlopitant Tablets	5 mg Serlopitant Tablets

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Worst Itch Numeric Rating Scale 4-point Responder Rate at Week 10	During the study, Worst Itch Numeric Rating Scale (WI-NRS) assessments was reported by the subject via eDiary. The daily NRS results were summarized. The daily results were averaged to create weekly measures. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity. It used a 24-hour recall period and asked subjects 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. A subject was a 4-point responder if their change from baseline is ≤ -4 (i.e. a decrease of at least 4).	At Week 10
WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8	During the study, Worst Itch Numeric Rating Scale (WI-NRS) assessments was reported by the subject via eDiary. The daily NRS results were summarized. The daily results were averaged to create weekly measures. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity. It used a 24-hour recall period and asked subjects 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. A subject was a 4-point responder if their change from baseline is ≤ -4 (i.e. a decrease of at least 4).	At Weeks 2, 4, 6, and 8
WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10	During the study, Worst Itch Numeric Rating Scale (WI-NRS) assessments was reported by the subject via eDiary. The daily NRS results were summarized. The daily results were averaged to create weekly measures. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity. It used a 24-hour recall period and asked subjects 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. A subject was a 3-point responder if their change from baseline is ≤ -3 (i.e. a decrease of at least 3). Results presented below is of subjects who were a 3-point responder but not a 4-point responder.	At Weeks 2, 4, 6, 8, and 10

Secondary Outcomes

Measure	Description	Time Frame
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Adverse events (AEs) were recorded to assess the safety and tolerability of repeated oral doses of serlopitant in adult subjects with chronic pruritus of unknown origin. Adverse events (AEs) and SAEs were recorded from the first study drug administration through the follow-up visit. After informed consent was signed, but prior to initiation of study drug, only SAEs considered by the investigator to be caused by a protocol-mandated intervention were collected.

Eligibility Module

Eligibility Criteria

Inclusion:

Male or female, age 18 years or older at consent.
The subject must have ongoing chronic pruritus
The subject's pruritus is assessed by the investigator to be of unknown origin at baseline.
Worst-Itch Numeric Rating Scale (WI-NRS) score in the 24-hour period prior to the Screening visit, and average weekly WI-NRS score in each of the 2 weeks prior to Baseline visit indicating an appropriate pruritus level for the study.
The pruritus must have been unresponsive to prior treatment with emollients.
The subject's pruritus must be present on multiple segments of the body
Willing and able to complete daily eDiary entries within a consistent timeframe for the duration of the study
All females who are of childbearing potential must be willing to practice highly effective contraception and not be pregnant or nursing
Willing to comply with study visits and study related requirements including providing written informed consent.
Adequate cognitive and physical ability, in the investigator's opinion, to comply with study visits and study related requirements including providing written informed consent

Exclusion

Prior treatment with any NK1-receptor antagonists
Known dermatologic or systemic condition(s), other than dry skin, that is considered by the investigator to be the primary cause of current pruritus.
Untreated or inadequately treated thyroid, adrenal, or pituitary disease or nodules, or history of thyroid malignancy.
Use of an excluded therapy within 3 weeks prior to randomization
Treatment with any investigational therapy within 3 weeks prior to randomization.
Serum creatinine, total bilirubin, alanine aminotransferase or aspartate aminotransferase > 2.5 times the upper limit of normal during screening.
History of malignancy within 3 years prior to randomization, with the (actinic keratosis, non-metastatic cutaneous squamous cell carcinoma, basal cell carcinoma of skin).
Any known major psychiatric diagnosis that would impact the subject's ability to complete the study
Suicidal ideation within 3 years prior to randomization, or any history of suicide attempt.
Known use of recreational drugs.
Documented history of parasitic infection, including skin parasites such as scabies, within 12 weeks prior to randomization.
Presence of clinically significant dementia, intellectual impairment, or any medical condition or disability that, in the investigator's opinion, could interfere with the assessment of safety or efficacy in this trial or compromise the safety of the subject.
History of hypersensitivity to serlopitant or any of its components.
Planned or anticipated major surgical procedure or other activity that would interfere with the subject's ability to comply with protocol-mandated assessments (e.g. extended international travel) during the subject's participation in the study.

Facility	Status	City	State	ZIP	Country	Contacts
Study Site 221		Hot Springs	Arkansas	72022	United States
Study Site 823

ID	Title	Description
FG000	Placebo	Randomized subjects received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.
FG001	Serlopitant 5 mg

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 11, 2019	Sep 2, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Worst Itch Numeric Rating Scale 4-point Responder Rate at Week 10

During the study, Worst Itch Numeric Rating Scale (WI-NRS) assessments was reported by the subject via eDiary. The daily NRS results were summarized. The daily results were averaged to create weekly measures.

The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity. It used a 24-hour recall period and asked subjects 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. A subject was a 4-point responder if their change from baseline is ≤ -4 (i.e. a decrease of at least 4).

Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.

Posted

Count of Participants

Participants

At Week 10

ID	Title	Description
OG000	Placebo	Randomized subjects received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.
OG001	Serlopitant 5 mg	Randomized subjects received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.

Units	Counts
Participants	OG000117 OG001116

Title

Denominators

Categories

Title	Measurements
	OG00046 OG00144

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	At Week 10	Cochran-Mantel-Haenszel		0.5861		Treatment Effect	-1.4			2-Sided	95	-13.9	11.1			95% Wald confidence intervals for the treatment difference was used		Superiority

Primary

WI-NRS 4-point Responder Rate at Weeks 2 4, 6, and 8

Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.

Posted

Count of Participants

Participants

At Weeks 2, 4, 6, and 8

ID	Title	Description
OG000	Placebo	Randomized subjects received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.
OG001	Serlopitant 5 mg	Randomized subjects received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.

Primary

WI-NRS 3-point Responder Rate at Weeks 2, 4, 6, 8, and 10

The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity. It used a 24-hour recall period and asked subjects 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. A subject was a 3-point responder if their change from baseline is ≤ -3 (i.e. a decrease of at least 3). Results presented below is of subjects who were a 3-point responder but not a 4-point responder.

Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.

Posted

Count of Participants

Participants

At Weeks 2, 4, 6, 8, and 10

ID	Title	Description
OG000	Placebo	Randomized subjects received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.
OG001	Serlopitant 5 mg	Randomized subjects received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.

Primary

Change From Baseline in WI-NRS at Weeks 2, 4, 6, 8, and 10

Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.

Posted

Mean

Standard Deviation

score on a scale

At Weeks 2, 4, 6, 8, and 10

ID	Title	Description
OG000	Placebo	Randomized subjects received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.
OG001	Serlopitant 5 mg	Randomized subjects received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.

Primary

Change From Baseline in Daily WI-NRS Scores Through Week 2

Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.

Posted

Mean

Standard Deviation

score on a scale

Through 2 weeks

ID	Title	Description
OG000	Placebo	Randomized subjects received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.
OG001	Serlopitant 5 mg	Randomized subjects received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.

Primary

Change From Baseline in Worst-Itch Visual Analog Scale at Weeks 2, 4, 6, and 10

The Itch Visual Analog Scale (VAS) is a validated, self-reported instrument for measurement of itch intensity. It used a 24-hour recall period and asked subjects to rate the worst intensity of their itch on a 100-mm horizontal line ranging from 0 mm (no itch) to 100 mm (worst itch imaginable). Higher scores indicated greater itch intensity. The VAS measurement were summarized in centimeters. WI-VAS assessments were reported by the subject via a paper form administered at study visits.

Full Analysis Population: subset of subjects in the randomized population who were dispensed study medication.

Posted

Mean

Standard Deviation

score on a scale

At Weeks 2, 4, 6, and 10

ID	Title	Description
OG000	Placebo	Randomized subjects received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.
OG001	Serlopitant 5 mg	Randomized subjects received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.

Secondary

Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Adverse events (AEs) were recorded to assess the safety and tolerability of repeated oral doses of serlopitant in adult subjects with chronic pruritus of unknown origin. Adverse events (AEs) and SAEs were recorded from the first study drug administration through the follow-up visit. After informed consent was signed, but prior to initiation of study drug, only SAEs considered by the investigator to be caused by a protocol-mandated intervention were collected.

Safety Population - Subset of subjects who received at least one dose of study medication

Posted

Count of Participants

Participants

From screening until the Follow-up (F/U) visit which occurred 35 days (+ 7 days) after the Week 10 visit or the last dose of study drug for subjects who discontinued study drug early.

ID	Title	Description
OG000	Placebo	Randomized subjects received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.
OG001	Serlopitant 5 mg	Randomized subjects received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.

Secondary

Plasma Concentrations of Serlopitant and Metabolites

The plasma concentrations of serlopitant and metabolites were combined with the data from other serlopitant clinical studies for population pharmacokinetic analysis.

Posted

Mean

Standard Deviation

nmol/L

At Week 10

ID	Title	Description
OG000	Placebo	Randomized subjects received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.
OG001	Serlopitant 5 mg	Randomized subjects received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.

Units	Counts
Participants	OG000

Term	Organ System	Assessment Type	Statistical Information
Intracranial mass	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected116 at risk
Metastasis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Non-systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected116 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected116 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Diarrhoea	Gastrointestinal disorders		Non-systematic Assessment		EG0000 affected117 at risk EG0018 affected116 at risk
Somnolence	Nervous system disorders		Non-systematic Assessment		EG0001 affected117 at risk EG0016 affected116 at risk

ID	Term
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D012877	Skin Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Placebo	Randomized subjects received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.
BG001	Serlopitant 5 mg	Randomized subjects received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Randomized subjects received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.	0	117	0	117	1	117
EG001	Serlopitant 5 mg	Randomized subjects received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, subjects took 1 tablet per day until the completion of the 10-week treatment period.	0	116	2	116	12	116