Substance P Challenge in Healthy Participants

GlaxoSmithKline32 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Skin Diseases

Interventions

Substance PDRUG

Participants will receive Substance P

Normal SalineDRUG

Participants will receive normal saline as Negative control

HistamineDRUG

Participants will receive histamine as Positive control

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

GSK Investigational Site

Leiden, Netherlands

Outcomes

Primary Outcomes

Part 1: Wheal Response-time Area Under the Curve (AUC) Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)

Wheal response-time AUC during the 2 hours post-challenge period following skin challenge for Substance P (SP) was calculated using the trapezoidal rule. The wheal response was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50, 150 and 500 picomoles (pmol) during the 2 hours post-challenge period.

Time frame: 0, 5, 10, 15, 20, 40, 60, 90 and 120 minutes post-challenge on Day 1 (Visit 1)

Part 2: Wheal Response-time AUC Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)

Wheal response-time AUC during the 2 hours post-challenge period following skin challenge for Substance P was calculated using the trapezoidal rule. The wheal response was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50 and 150 pmol during the 2 hours post-challenge period.

Time frame: 0, 5, 10, 15, 20, 30, 40, 60, 90 and 120 minutes post-challenge on Day 1 (Visit 1) and on Week 2 (Visit 2)

Secondary Outcomes

Part 1: Maximum Observed Wheal Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)

Wheal area was calculated using the following formula: 1/4 \* pi \* longest diameter \* orthogonal diameter, for area of an ellipse, using the longest and orthogonal diameters measured by the calliper method. The maximum observed wheal area was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50, 150 and 500 pmol during the 2 hours post-challenge period.

Time frame: 2 hours post-challenge on Day 1 (Visit 1)

Part 2: Maximum Observed Wheal Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P Across- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Wheal area was calculated using the following formula: 1/4 \* pi \* longest diameter \* orthogonal diameter, for area of an ellipse, using the longest and orthogonal diameters measured by the calliper method. The maximum observed wheal area was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50 and 150 pmol during the 2 hours post-challenge period.

Time frame: 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge at Week 2 (Visit 2)

Part 1: Time to Maximum Observed Wheal Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)

Time to maximum observed wheal area was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50, 150 and 500 pmol during the 2 hours post-challenge period.

Time frame: 2 hours post-challenge on Day 1 (Visit 1)

Part 2: Time to Maximum Observed Wheal Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)

Time to maximum observed wheal area was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50 and 150 pmol during the 2 hours post-challenge period.

Time frame: 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge at Week 2 (Visit 2)

Part 1: Time to Complete Wheal Area Disappearance Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)

Time to complete wheal area disappearance was calculated during the 2 hours post-challenge period. Complete disappearance is defined as a value of 0 for wheal area, longest diameter or orthogonal diameter. Participants who did not have a disappearance within the 2 hours post challenge period were excluded. Time to complete wheal area disappearance was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50, 150 and 500 pmol during the 2 hours post-challenge period.

Time frame: 2 hours post-challenge on Day 1 (Visit 1)

Part 2: Time to Complete Wheal Area Disappearance Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)

Time to complete wheal area disappearance was calculated during the 2 hours post-challenge period. Complete disappearance is defined as a value of 0 for wheal area, longest diameter or orthogonal diameter. Participants who did not have a disappearance within the 2 hours post challenge period were excluded. Time to complete wheal area disappearance was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50 and 150 pmol during the 2 hours post-challenge period.

Time frame: 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge at Week 2 (Visit 2)

Part 1: Flare Response-time AUC Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)

Flare response-time AUC during the 2 hours post-challenge period following skin challenge for Substance P was calculated using the trapezoidal rule. The flare response was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50, 150 and 500 pmol during the 2 hours post-challenge period.

Time frame: 0, 5, 10, 15, 20, 40, 60, 90 and 120 minutes post-challenge on Day 1 (Visit 1)

Part 2: Flare Response-time AUC Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)

Flare response-time AUC during the 2 hours post-challenge period following skin challenge for Substance P was calculated using the trapezoidal rule. The flare response variable was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50 and 150 pmol during the 2 hours post-challenge period.

Time frame: 0, 5, 10, 15, 20, 30, 40, 60, 90 and 120 minutes post-challenge on Day 1 (Visit 1) and on Week 2 (Visit 2)

Part 1: Maximum Observed Flare Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)

Flare area was calculated using the following formula: 1/4 \* pi \* longest diameter \* orthogonal diameter, for area of an ellipse, using the longest and orthogonal diameters measured by the calliper method. The maximum observed flare area was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50, 150 and 500 pmol during the 2 hours post-challenge period.

Time frame: 2 hours post-challenge on Day 1 (Visit 1)

Part 2: Maximum Observed Flare Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P Across- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)

Flare area was calculated using the following formula: 1/4 \* pi \* longest diameter \* orthogonal diameter, for area of an ellipse, using the longest and orthogonal diameters measured by the calliper method. The maximum observed flare area was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50 and 150 pmol during the 2 hours post-challenge period.

Time frame: 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge At Week 2 (Visit 2)

Part 1: Time to Maximum Observed Flare Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)

Time to maximum observed flare area was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50, 150 and 500 pmol during the 2 hours post-challenge period.

Time frame: 2 hours post-challenge on Day 1 (Visit 1)

Part 2: Time to Maximum Observed Flare Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)

Time to maximum observed flare area was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50 and 150 pmol during the 2 hours post-challenge period.

Time frame: 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge At Week 2 (Visit 2)

Part 1: Time to Complete Flare Area Disappearance Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)

Time to complete flare area disappearance was calculated during the 2 hours post-challenge period. Complete disappearance is defined as a value of 0 for flare area, longest diameter or orthogonal diameter. Participants who did not have a disappearance within the 2 hours post challenge period were excluded. Time to complete wheal area disappearance was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50, 150 and 500 pmol during the 2 hours post-challenge period.

Time frame: 2 hours post-challenge on Day 1 (Visit 1)

Part 2: Time to Complete Flare Area Disappearance Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)

Time to complete flare area disappearance was calculated during the 2 hours post-challenge period. Complete disappearance is defined as a value of 0 for wheal area, longest diameter or orthogonal diameter. Participants who did not have a disappearance within the 2 hours post challenge period were excluded. Time to complete wheal area disappearance was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50 and 150 pmol during the 2 hours post-challenge period.

Time frame: 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge At Week 2 (Visit 2)

Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)- Substance P Only

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with non-serious AEs and SAEs is presented.

Time frame: Up to Day 1

Part 2: Number of Participants With Non-serious AEs and SAEs- Substance P Only

Time frame: Up to 3 weeks

Part 1: Number of Participants With Worst Case Vital Signs Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1)

Vital signs parameters including Systolic blood pressure (SBP), Diastolic blood pressure (DBP) and heart rate were measured in a semi-supine position after 5 minutes of rest with a completely automated device. PCI ranges were: SBP (Lower: less than \[\<\]85 and Upper: greater than \[\>\]160 millimeters of mercury \[mmHg\]); DBP (Lower: \<45 and Upper: \>100 mmHg); Heart Rate: (Lower: \<40 and Upper: \>110 beats per minute). Baseline value is defined as the latest non-missing pre-first control challenge assessment value at challenge visit 1, including those from unscheduled visits. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages (%) may not add to 100%.

Time frame: At Day 1 (Visit 1)

Part 2: Number of Participants With Worst Case Vital Signs Parameter Results by Potential Clinical Importance (PCI) Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)

Vital signs parameters including SBP, DBP and heart rate were measured in a semi-supine position after 5 minutes of rest with a completely automated device. PCI ranges were: SBP (Lower: \<85 and Upper: \>160 mmHg); DBP (Lower: \<45 and Upper: \>100 mmHg); Heart Rate: (Lower: \<40 and Upper: \>110 beats per minute). Baseline value is defined as the latest non-missing pre-first control challenge assessment value at challenge visit 1 and challenge visit 2, including those from unscheduled visits. For Part 2, the Baseline for Visit 2 is defined as the latest assessment performed after Visit 1 visits (such as Unscheduled) but before the first Visit 2 challenge. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the % may not add to 100%.

Time frame: At Day 1 (Visit 1) and Week 2 (Visit 2)

Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophil Count, Platelet Count and White Blood Cell Count- Substance P Only at Challenge Visit 1 (Day 1)

Blood samples were collected for the analysis of hematology parameters: basophils, eosinophils, lymphocytes, monocytes, total neutrophil count, platelet count and white blood cell count. Baseline value is defined as the latest non-missing pre-first control challenge assessment value (Within 1 hour before first control challenge) at challenge visit 1, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.