Study of the Efficacy, Safety and Tolerability of Serlopi... | NCT03546816

Status Module

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

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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent of Subjects With Worst-Itch Numeric Rating Scale 4-point Responder at Week 10	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.	At Week 10

Secondary Outcomes

Measure	Description	Time Frame
Percent of Subjects With WI-NRS 4-point Responder at Week 4	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria (Subjects must meet the following criteria to be randomized into the study:

Male or female, age 18 years or older at consent.
Prurigo nodularis (PN), with at least ten nodules on at least two different body surface areas.
Idiopathic PN, or an identified pruritic condition associated with the PN with persistent pruritus despite at least 6 weeks of optimized and stable treatment of the underlying condition.
The worst pruritus is identified as within the areas of the PN lesions, with a 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.
Female subjects of childbearing potential must be willing to practice highly effective contraception until 5 weeks after last dose of study drug.
Willing and able to complete daily eDiary entries within a consistent timeframe for the duration of the study.
Willing and able to comply with study visits and study related requirements including providing written informed consent.

Exclusion Criteria (Subjects who meet any of the following criteria are not eligible for participation in the study):

Prior treatment with serlopitant.
Active pruritic skin disease, other than PN, within 6 months (with the exception of acute dermatoses such as contact dermatitis, sunburn, viral exanthem, which have been resolved for longer than 4 weeks).
Treatment with any of the following therapies within 4 weeks.
1. Other neurokinin-1 receptor antagonists (e.g., aprepitant, fosaprepitant, rolapitant).
2. Systemic or topical immunosuppressive/immunomodulatory therapies.
3. Systemic therapies with recognized anti-pruritic properties.
4. Strong cytochrome-P 3A4 inhibitors.
5. Use of an indoor tanning facility, or natural sun exposure resulting in significant tanning or sunburn.
Treatment with topical anti-pruritic therapies within 2 weeks.
Treatment with biologic therapies within 8 weeks or 5 half-lives, whichever is longer.
Treatment with any investigational therapy within 4 weeks (8 weeks for investigational biologic therapies) or 5 half-lives, whichever is longer.
Serum creatinine, total bilirubin, alanine aminotransferase or aspartate aminotransferase > 2.5 times the upper limit of normal during screening.
Untreated or inadequately treated thyroid adrenal, or pituitary nodules or disease, or history of thyroid malignancy.
Malignancy within 5 years prior to enrollment (exception for non-melanoma cutaneous malignancies).
Relevant major psychiatric diagnosis in the past 3 years, such as major depressive disorder, bipolar disorder, schizophrenia, psychotic disorder, intellectual disability, severe alcohol use disorder.
Documented history of parasitic infection, including skin parasites such as scabies, within 8 weeks.
Any medical condition or disability that could interfere with the assessment of safety or efficacy in this study or compromise the safety of the subject.
History of hypersensitivity to serlopitant or any of its components.
Currently pregnant or breastfeeding or planning to become pregnant during the study.
Planned or anticipated major surgical procedure or other activity that would interfere with the subject's ability to comply with protocol-mandated assessments during participation in the study.

Facility	Status	City	State	ZIP	Country	Contacts
Study Site 504		Birmingham	Alabama	35233	United States
Study Site 533

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 16, 2019	Aug 18, 2020

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

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).

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG00026.45 OG00120.31

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		Cochran-Mantel-Haenszel		0.229	P-value from a Cochran-Mantel-Haenszel (CMH) test stratified by Baseline WI-NRS used for randomization stratification. Value has been adjusted for multiple imputation.													Superiority

Secondary

Percent of Subjects With WI-NRS 4-point Responder at Week 4

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.

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

Posted

Number

Percentage of subjects

At Week 4

ID	Title	Description
OG000	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 on an outpatient basis.
OG001	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 on an outpatient basis.

Units

Secondary

Percent of Subjects With WI-NRS 4-point Responder at Week 2

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

Posted

Number

Percentage of subjects

At Week 2

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts

Secondary

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

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

Posted

Mean

Standard Deviation

Score on a scale

At Weeks 2, 4, 6, and 10

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts

Secondary

Percent of Subjects With WI-NRS 3-point Responder at Weeks 2, 4, and 10

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

Posted

Number

Percentage of subjects

At Weeks 2, 4, and 10

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Change From Baseline in Investigator's Global Assessment of Prurigo Nodularis Activity (IGA PN-A) to Weeks 2, 4, and 10

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.

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

Posted

Mean

Standard Deviation

Score on a scale

At Weeks 2, 4, and 10

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

Change From Baseline in Investigator's Global Assessment of PN Stage (IGA PN-S) to Weeks 2, 4, and 10

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.

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

Posted

Mean

Standard Deviation

Score on a scale

At Weeks 2, 4, and 10

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 10

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.

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

Posted

Mean

Standard Deviation

Score on a scale

At Week 10

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Change From Baseline in DLQI Question 1 to Week 10

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.

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

Posted

Mean

Standard Deviation

Score on a scale

At Week 10

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events (SAEs)

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.

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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.
OG001	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA v21.1	Non-systematic Assessment	EG0001 affected139 at risk EG0010 affected141 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA v21.1	Non-systematic Assessment	EG0001 affected139 at risk EG0010 affected141 at risk
Schizoaffective disorder	Psychiatric disorders	MedDRA v21.1	Non-systematic Assessment	EG0001 affected139 at risk EG0010 affected141 at risk
Haematochezia	Gastrointestinal disorders	MedDRA v21.1	Non-systematic Assessment	EG0001 affected139 at risk EG0010 affected141 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v21.1	Non-systematic Assessment	EG0001 affected139 at risk EG0010 affected141 at risk
Pneumonia	Infections and infestations	MedDRA v21.1	Non-systematic Assessment	EG0001 affected139 at risk EG0010 affected141 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA v21.1	Non-systematic Assessment	EG0001 affected139 at risk EG0010 affected141 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA v21.1	Non-systematic Assessment	EG0000 affected139 at risk EG0011 affected141 at risk
Abscess limb	Infections and infestations	MedDRA v21.1	Non-systematic Assessment	EG0000 affected139 at risk EG0011 affected141 at risk
Knee arthroplasty	Surgical and medical procedures	MedDRA v21.1	Non-systematic Assessment	EG0000 affected139 at risk EG0011 affected141 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	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.
BG001	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.
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	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.	0	139	6	139	18	141
EG001	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.	0	141	3	141	5	139

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Upper respiratory tract infection	Infections and infestations	MedDRA v21.1	Non-systematic Assessment		EG00010 affected141 at risk EG0013 affected139 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA v21.1	Non-systematic Assessment		EG0009 affected141 at risk EG0012 affected139 at risk