Substance P Challenge in Healthy Participants

• Status: Completed
• Trial end date: 2021-07-21
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: GlaxoSmithKline
• Treatments: Histamine; Neurokinin A; Substance P

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.