Substance P Challenge in Healthy Participants

Study Overview
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Brief Summary
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The objectives of this enabling study are to characterize the wheal and flare responses over time following skin challenges with ascending concentrations of Substance P. This will be a 2-part study: Part 1 will aid in the understanding of the wheal and flare responses following Substance P. Part 2 will investigate the variability of the responses. Participants may be enrolled into Part 1 or Part 2, not both.

Official Title
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An Open Label, Single Centre, Enabling Study to Investigate the Optimum Method for Use of Intradermal Substance P as a Challenge Agent in Healthy Participants

Conditions
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Skin Diseases

Intervention / Treatment
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* Drug: Substance P
* Drug: Normal Saline
* Drug: Histamine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 18 to 50 years of age inclusive. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, ECGs and vital signs. Participants who responded positive to histamine skin prick test and negative to saline injection at screening. Participants with Fitzpatrick skin type I-II (Caucasian). Body weight greater than or equal to (>=) 50 kilogram (kg) and body mass index (BMI) within the range 19-29.9 kilogram per meter square (kg/m2) (inclusive). Male participants are eligible to participate in the study. A female participant is eligible to participate if she is not pregnant or breastfeeding or using highly effective contraceptive methods. Woman of non-childbearing potential can also participate. A sensitive pregnancy test is required to be negative on the day of each challenge. Capable of giving signed informed consent. Exclusion Criteria: Significant history of or current, cardiovascular (including hypotension, severe hypertension, vasomotor instability), respiratory (including asthma), renal, gastrointestinal, endocrine, hematological, infectious or neurological disorders constituting a risk when taking part in the study or interfering with the interpretation of data. History or presence of significant skin disorder (such as but not limited to chronic urticaria, atopic dermatitis, severe eczema, psoriasis or skin cancer). History of risk for or actual experience of complications from skin biopsy including excess bleeding, infection, or scarring/keloid formation. Abnormal blood pressure as determined by the investigator. Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN). Total bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if total bilirubin is fractionated and direct bilirubin <35%). Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 millisecond (msec), based on the mean of triplicate ECGs. Use of any form of H1 or H2 antihistamine, tricyclic antidepressants, beta2 agonists, dopamine, or beta blocking agents within 14 days before the first challenge visit through final assessments. Use of topical medications such as but not limited to retinoids, steroids, and transdermal hormone replacement therapies on or near the intended site of application within 8 weeks prior to dosing through treatment follow up. Use of other topical preparations such as those containing vitamins, supplements or herbal within 2 weeks prior to dosing through treatment follow up. Past or intended use of any other non-topical over-the-counter or prescription medication, including herbal medications, within 7 days before the first challenge visit, unless, in the opinion of the investigator and GlaxoSmithKline medical monitor, the medication will not constitute a risk when taking the study intervention or interfere with the interpretation of data. Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 3 months. Current enrolment in any clinical study involving an investigational study intervention or any other type of medical research. Current enrolment or past participation in this study. Presence of Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HbcAb) at screening or within 3 months before the first challenge day. Positive Hepatitis C antibody test result at screening or within 3 months before the first challenge day. Positive Hepatitis C RNA test result at screening or within 3 months before the first challenge day. Positive pre-study drug/alcohol screen. Positive human immunodeficiency virus (HIV) antibody test at screening or within 3 months before the first challenge day. Current use of known drugs of abuse. Participants who present with damaged skin including sunburn, scar tissue, moles, uneven skin tones and dark skin tone (Fitzpatrick>2), tattoos, body piercings, branding or other skin disfiguration on or near the intended site of application which could interfere with the assessments Regular alcohol consumption within 6 months before the study defined as an average weekly intake of >21 units for males or >14 units for females. Smoking test result indicative of smoking, history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study. Unable to refrain from the use of topical medications from before the first to after the last challenge visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Parts 1 and 2 will run sequentially. Part 1 will include 1 challenge visit; Part 2 will include two challenge visits.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Substance P challenge in Part 1<br>Eligible participants will receive control challenge with saline and histamine, followed by challenge with ascending concentrations of Substance P. Part 1 will include a single challenge visit. | Drug: Substance P<br>* Participants will receive Substance P<br>Drug: Normal Saline<br>* Participants will receive normal saline as Negative control<br>Drug: Histamine<br>* Participants will receive histamine as Positive control<br>|
| Experimental: Substance P challenge in Part 2<br>Eligible participants will receive control challenge with saline and histamine, followed by challenge with ascending concentrations of Substance P. Part 2 will include two challenge visits. | Drug: Substance P<br>* Participants will receive Substance P<br>Drug: Normal Saline<br>* Participants will receive normal saline as Negative control<br>Drug: Histamine<br>* Participants will receive histamine as Positive control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Area under the curve (AUC) over the post-challenge period for Substance P to characterize wheal response over time |  | Day 1 | 
| Part 2: AUC over the post-challenge period for Substance P to characterize wheal response over time |  | Up to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Maximum observed wheal response during the post challenge period for Substance P (response will be area in millimeters squared) |  | Day 1 | 
| Part 2: Maximum observed wheal response during the post challenge period for Substance P (response will be area in millimeters squared) |  | Up to Day 14 | 
| Part 1: Time to maximum observed wheal response during the post challenge period for Substance P |  | Day 1 | 
| Part 2: Time to maximum observed wheal response during the post challenge period for Substance P |  | Up to Day 14 | 
| Part 1: Time of complete wheal response disappearance during the post challenge period for Substance P |  | Day 1 | 
| Part 2: Time of complete wheal response disappearance during the post challenge period for Substance P |  | Up to Day 14 | 
| Part 1: AUC during the post challenge period for Substance P to characterize flare response over time |  | Day 1 | 
| Part 2: AUC during the post challenge period for Substance P to characterize flare response over time |  | Up to Day 14 | 
| Part 1: Maximum observed flare response during the post challenge period for Substance P (response will be area in millimeters squared) |  | Day 1 | 
| Part 2: Maximum observed flare response during the post challenge period for Substance P (response will be area in millimeters squared) |  | Up to Day 14 | 
| Part 1: Time to maximum observed flare response during the post challenge period for Substance P |  | Day 1 | 
| Part 2: Time to maximum observed flare response during the post challenge period for Substance P |  | Up to Day 14 | 
| Part 1: Time of complete flare response disappearance during the post challenge period for Substance P |  | Day 1 | 
| Part 2: Time of complete flare response disappearance during the post challenge period for Substance P |  | Up to Day 14 | 
| Part 1: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Day 1 | 
| Part 2: Number of participants with AEs and SAEs |  | Up to 3 weeks | 
| Part 1: Number of participants with clinically significant changes in vital signs, laboratory parameters, and 12-lead electrocardiogram (ECG) findings |  | Day 1 | 
| Part 2: Number of participants with clinically significant changes in vital signs, laboratory parameters, and 12-lead ECG findings |  | Up to 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Substance P, Wheal response, Flare response, Skin challenge