substance p challenge in healthy participants

Conditions: Skin Diseases

Summary: 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.


Eligibility criteria:
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.

Keywords: substance p wheal response flare response skin challenge