Skin Diseases
Conditions
Keywords
Substance P, Wheal response, Flare response, Skin challenge
Brief 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.
Interventions
DRUGSubstance P
Participants will receive Substance P
DRUGNormal Saline
Participants will receive normal saline as Negative control
DRUGHistamine
Participants will receive histamine as Positive control
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Masking description
It is an open-label study.
Intervention model description
Parts 1 and 2 will run sequentially. Part 1 will include 1 challenge visit; Part 2 will include two challenge visits.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 0, 5, 10, 15, 20, 40, 60, 90 and 120 minutes post-challenge on Day 1 (Visit 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. |
| 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) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 2 hours post-challenge on Day 1 (Visit 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. |
| 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) | 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge at Week 2 (Visit 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. |
| 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) | 2 hours post-challenge on Day 1 (Visit 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. |
| 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) | 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge at Week 2 (Visit 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. |
| 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) | 0, 5, 10, 15, 20, 40, 60, 90 and 120 minutes post-challenge on Day 1 (Visit 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. |
| 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) | 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) | 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. |
| 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) | 2 hours post-challenge on Day 1 (Visit 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. |
| 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) | 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge At Week 2 (Visit 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. |
| 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) | 2 hours post-challenge on Day 1 (Visit 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. |
| 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) | 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge At Week 2 (Visit 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. |
| 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) | 2 hours post-challenge on Day 1 (Visit 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. |
| 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) | 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge At Week 2 (Visit 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. |
| Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)- Substance P Only | Up to Day 1 | 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. |
| Part 2: Number of Participants With Non-serious AEs and SAEs- Substance P Only | Up to 3 weeks | 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. |
| 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) | At Day 1 (Visit 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%. |
| 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) | At Day 1 (Visit 1) and Week 2 (Visit 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%. |
| 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) | Baseline (Day 1: pre-dose) and At Day 1 (Visit 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. |
| Part 2: 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 2 (Week 2) | Baseline (Day 1: pre-dose) and At Week 2 (Visit 2) | Blood samples were collected for the analysis of hematology parameters: Basophils, eosinophils, lymphocytes, monocytes, total neutrophil count, platelet count and white blood cell count. 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. Change from Baseline was defined as post-dose visit value minus Baseline value. |
| Part 1: Change From Baseline in Hematology Parameter: Hemoglobin- Substance P Only at Challenge Visit 1 (Day 1) | Baseline (Day 1: pre-dose) and At Day 1 (Visit 1) | Blood samples were collected for the analysis of hematology parameter: Hemoglobin. 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. |
| Part 2: Change From Baseline in Hematology Parameter: Hemoglobin- Substance P Only at Challenge Visit 2 (Week 2) | Baseline (Day 1: pre-dose) and At Week 2 (Visit 2) | Blood samples were collected for the analysis of hematology parameter: Hemoglobin. 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. Change from Baseline was defined as post-dose visit value minus Baseline value. |
| Part 1: Change From Baseline in Hematology Parameter: Hematocrit- Substance P Only at Challenge Visit 1 (Day 1) | Baseline (Day 1: pre-dose) and At Day 1 (Visit 1) | Blood samples were collected for the analysis of hematology parameter: Hematocrit. 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. |
| Part 2: Change From Baseline in Hematology Parameter: Hematocrit- Substance P Only at Challenge Visit 2 (Week 2) | Baseline (Day 1: pre-dose) and At Week 2 (Visit 2) | Blood samples were collected for the analysis of hematology parameter: Hematocrit. 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. Change from Baseline was defined as post-dose visit value minus Baseline value. |
| Part 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin- Substance P Only at Challenge Visit 1 (Day 1) | Baseline (Day 1: pre-dose) and At Day 1 (Visit 1) | Blood samples were collected for the analysis of hematology parameter: Mean corpuscle hemoglobin. 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. |
| Part 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin- Substance P Only at Challenge Visit 2 (Week 2) | Baseline (Day 1: pre-dose) and At Week 2 (Visit 2) | Blood samples were collected for the analysis of hematology parameter: Mean corpuscle hemoglobin. 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. Change from Baseline was defined as post-dose visit value minus Baseline value. |
| Part 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume- Substance P Only at Challenge Visit 1 (Day 1) | Baseline (Day 1: pre-dose) and At Day 1 (Visit 1) | Blood samples were collected for the analysis of hematology parameter: Mean corpuscle volume. 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. |
| Part 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume- Substance P Only at Challenge Visit 2 (Week 2) | Baseline (Day 1: pre-dose) and At Week 2 (Visit 2) | Blood samples were collected for the analysis of hematology parameter: Mean corpuscle volume. 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. Change from Baseline was defined as post-dose visit value minus Baseline value. |
| Part 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count- Substance P Only at Challenge Visit 1 (Day 1) | Baseline (Day 1: pre-dose) and At Day 1 (Visit 1) | Blood samples were collected for the analysis of hematology parameter: Red 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. |
| Part 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count- Substance P Only at Challenge Visit 2 (Week 2) | Baseline (Day 1: pre-dose) and At Week 2 (Visit 2) | Blood samples were collected for the analysis of hematology parameter: Red blood cell count. 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. Change from Baseline was defined as post-dose visit value minus Baseline value. |
| Part 1: Change From Baseline in Hematology Parameter: Reticulocyte- Substance P Only at Challenge Visit 1 (Day 1) | Baseline (Day 1: pre-dose) and At Day 1 (Visit 1) | Blood samples were collected for the analysis of hematology parameter: Reticulocyte. 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. |
| Part 2: Change From Baseline in Hematology Parameter: Reticulocyte- Substance P Only at Challenge Visit 2 (Week 2) | Baseline (Day 1: pre-dose) and At Week 2 (Visit 2) | Blood samples were collected for the analysis of hematology parameter: Reticulocyte. 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. Change from Baseline was defined as post-dose visit value minus Baseline value. |
| Part 1: Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase and Aspartate Aminotransferase- Substance P Only at Challenge Visit 1 (Day 1) | Baseline (Day 1: pre-dose) and At Day 1 (Visit 1) | Blood samples were collected for the analysis of clinical chemistry parameters: Alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. 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. |
| Part 2: Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase and Aspartate Aminotransferase- Substance P Only at Challenge Visit 2 (Week 2) | Baseline (Day 1: pre-dose) and At Week 2 (Visit 2) | Blood samples were collected for the analysis of clinical chemistry parameters: Alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. 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. Change from Baseline was defined as post-dose visit value minus Baseline value. |
| Part 1: Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine- Substance P Only at Challenge Visit 1 (Day 1) | Baseline (Day 1: pre-dose) and At Day 1 (Visit 1) | Blood samples were collected for the analysis of clinical chemistry parameters: Total Bilirubin and creatinine. 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. |
| Part 2: Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine- Substance P Only at Challenge Visit 2 (Week 2) | Baseline (Day 1: pre-dose) and At Week 2 (Visit 2) | Blood samples were collected for the analysis of clinical chemistry parameters: Total bilirubin and creatinine. 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. Change from Baseline was defined as post-dose visit value minus Baseline value. |
| Part 1: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN)- Substance P Only at Challenge Visit 1 (Day 1) | Baseline (Day 1: pre-dose) and At Day 1 (Visit 1) | Blood samples were collected for the analysis of clinical chemistry parameters: Calcium, glucose, potassium, sodium, and urea/BUN. 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. |
| Part 2: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/BUN- Substance P Only at Challenge Visit 2 (Week 2) | Baseline (Day 1: pre-dose) and At Week 2 (Visit 2) | Blood samples were collected for the analysis of clinical chemistry parameters: Calcium, glucose, potassium, sodium, and urea/BUN. 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. Change from Baseline was defined as post-dose visit value minus Baseline value. |
| Part 1: Change From Baseline in Clinical Chemistry Parameter: Total Protein- Substance P Only at Challenge Visit 1 (Day 1) | Baseline (Day 1: pre-dose) and At Day 1 (Visit 1) | Blood samples were collected for the analysis of clinical chemistry parameter: Total protein. 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. |
| Part 2: Change From Baseline in Clinical Chemistry Parameter: Total Protein- Substance P Only at Challenge Visit 2 (Week 2) | Baseline (Day 1: pre-dose) and At Week 2 (Visit 2) | Blood samples were collected for the analysis of clinical chemistry parameter: Total protein. 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. Change from Baseline was defined as post-dose visit value minus Baseline value. |
| 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) | 2 hours post-challenge on Day 1 (Visit 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. |
| Part 2: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 2 (Week 2) | At Week 2 (Visit 2) | Urine samples were collected for the analysis of urinalysis parameters: Occult blood, glucose, ketones and protein by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters indicate proportional concentrations in the urine sample. Number of participants with abnormal results were reported as 'Any increase' if there was any increase in their urine concentrations compared to Baseline. Participants whose value was unchanged or whose value was decreased, were recorded in the 'No change/Decreased' category. 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. |
| Part 1: Number of Participants With Clinically Significant Abnormal 12-lead Electrocardiogram (ECG) Findings- Substance P Only at Challenge Visit 1 (Day 1) | At Day 1 (Visit 1) | 12-lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and corrected QT (QTc) intervals and calculated heart rate. Data for abnormal, clinically significant (CS) ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. |
| Part 2: Number of Participants With Clinically Significant Abnormal 12-lead ECG Findings- Substance P Only at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2) | At Day 1 (Visit 1) and Week 2 (Visit 2) | 12-lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and QTc intervals and calculated heart rate. Data for abnormal, CS ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. |
| Part 1: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1) | At Day 1 (Visit 1) | Urine samples were collected for the analysis of urinalysis parameters: Occult blood, glucose, ketones and protein by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters indicate proportional concentrations in the urine sample. Number of participants with abnormal results were reported as 'Any increase' if there was any increase in their urine concentrations compared to Baseline. Participants whose value was unchanged or whose value was decreased, were recorded in the 'No change/Decreased' category. Baseline value is defined as the latest non-missing pre-first control challenge assessment value at challenge visit 1, including those from unscheduled visits. |
| 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) | 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge at Week 2 (Visit 2) | 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. |
Countries
Netherlands
Participant flow
Recruitment details
This was an open label, 2-part, sequential, prospective enabling study of Substance P (SP) intradermal challenge in healthy participants conducted at a single center in the Netherlands.
Pre-assignment details
A total of 32 participants were enrolled (Enrolled population: All participants in the screened population who entered the study) in Part 1 (12 participants) and Part 2 (20 participants) of the study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1- Skin Challenges Healthy participants were first administered saline, by intradermal injection, and histamine by skin prick, as negative and positive controls. Participants with acceptable saline and histamine responses, were administered up to 4 intradermal injections of Substance P sequentially from lowest to highest concentration (5, 15, 50, 150 and 500 picomole \[PMOL\]) at challenge visit 1 (Day 1) and wheal and flare responses were assessed. There was no Challenge Visit 2 in Part 1. | 9 |
| Part 1- No Skin Challenges Healthy participants were first administered saline, by intradermal injection, and histamine by skin prick, as negative and positive controls. Participants whose wheal responses did not meet the acceptable saline and histamine response within 20 minutes of each control challenge or who were withdrawn from the study, independent of the wheal response acceptability, were not administered Substance P. | 3 |
| Part 2- Skin Challenges Healthy participants were first administered saline, by intradermal injection, and histamine by skin prick, as negative and positive controls. Participants with acceptable saline and histamine responses were administered up to 4 intradermal injections of Substance P sequentially from lowest to highest concentration (5, 15, 50 and 150 PMOL) and wheal and flare responses were assessed along with Intradermal microdialysis (IDM) after Challenge Visit 1 (Day 1). At Challenge Visit 2 (Week 2), participants were administered up to 6 Substance P intradermal injections and wheal and flare response, IDM and biopsies were taken (one from each challenged site and one from a non-challenged area of skin. | 20 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part 1 (Up to Day 1) | Physician Decision | 0 | 1 | 0 |
| Part 1 (Up to Day 1) | Protocol Violation | 0 | 1 | 0 |
| Part 1 (Up to Day 1) | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1- Skin Challenges | Part 1- No Skin Challenges | Part 2- Skin Challenges | Total |
|---|---|---|---|---|
| Age, Continuous | 23.0 Years STANDARD_DEVIATION 3.5 | 22.0 Years STANDARD_DEVIATION 4.58 | 26.8 Years STANDARD_DEVIATION 9.34 | 25.3 Years STANDARD_DEVIATION 7.88 |
| Race/Ethnicity, Customized White- Arabic / North African Heritage | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White- White/ Caucasian/ European Heritage | 9 Participants | 3 Participants | 18 Participants | 30 Participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 13 Participants | 20 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 7 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 20 |
| other Total, other adverse events | 1 / 9 | 2 / 20 |
| serious Total, serious adverse events | 0 / 9 | 0 / 20 |
Outcome results
Primary
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)
Population: Safety Population consisted of all participants in the enrolled analysis set who received at least one challenge-related study procedure on their (first) challenge day. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | 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) | SP 15 pmol | 5727.2220 Millimeter square*minutes | Standard Deviation 3859.78704 |
| Part 1- Skin Challenges | 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) | Saline | 155.2379 Millimeter square*minutes | Standard Deviation 97.43852 |
| Part 1- Skin Challenges | 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) | Histamine | 2151.2320 Millimeter square*minutes | Standard Deviation 1352.66124 |
| Part 1- Skin Challenges | 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) | SP 5 pmol | 2749.0997 Millimeter square*minutes | Standard Deviation 2000.66201 |
| Part 1- Skin Challenges | 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) | SP 50 pmol | 7111.5570 Millimeter square*minutes | Standard Deviation 5388.48885 |
| Part 1- Skin Challenges | 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) | SP 150 pmol | 8295.6310 Millimeter square*minutes | Standard Deviation 5912.58152 |
| Part 1- Skin Challenges | 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) | SP 500 pmol | 12540.9840 Millimeter square*minutes | Standard Deviation 14705.68961 |
Primary
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | 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) | Saline: 2 hours post-challenge on Day 1 | 157.9157 Millimeter square*minutes | Standard Deviation 110.11185 |
| Part 1- Skin Challenges | 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) | Saline: 2 hours post-challenge at Week 2 | 216.5196 Millimeter square*minutes | Standard Deviation 113.81519 |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge on Day 1 | 2617.3622 Millimeter square*minutes | Standard Deviation 1362.88319 |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge at Week 2 | 2486.9477 Millimeter square*minutes | Standard Deviation 1171.55762 |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge on Day 1 | 4534.4513 Millimeter square*minutes | Standard Deviation 2153.69897 |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge at Week 2 | 4563.5113 Millimeter square*minutes | Standard Deviation 2517.52789 |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge on Day 1 | 6754.7067 Millimeter square*minutes | Standard Deviation 3501.44122 |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge at Week 2 | 6506.0915 Millimeter square*minutes | Standard Deviation 3199.02966 |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge on Day 1 | 8937.9117 Millimeter square*minutes | Standard Deviation 4089.24955 |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge at Week 2 | 9763.2271 Millimeter square*minutes | Standard Deviation 4963.46223 |
| Part 1- Skin Challenges | 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) | SP 150 pmol:2 hours post-challenge on Day 1 | 11017.5544 Millimeter square*minutes | Standard Deviation 4779.69981 |
| Part 1- Skin Challenges | 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) | SP 150 pmol: 2 hours post-challenge at Week 2 | 9977.7777 Millimeter square*minutes | Standard Deviation 4155.85567 |
Secondary
Part 1: Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase and Aspartate Aminotransferase- Substance P Only at Challenge Visit 1 (Day 1)
Blood samples were collected for the analysis of clinical chemistry parameters: Alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. 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.
Time frame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase and Aspartate Aminotransferase- Substance P Only at Challenge Visit 1 (Day 1) | Alkaline phosphatase | 71.1 International units per liter | Standard Deviation 18.38 |
| Part 1- Skin Challenges | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase and Aspartate Aminotransferase- Substance P Only at Challenge Visit 1 (Day 1) | Alanine aminotransferase | 19.0 International units per liter | Standard Deviation 8.82 |
| Part 1- Skin Challenges | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase and Aspartate Aminotransferase- Substance P Only at Challenge Visit 1 (Day 1) | Aspartate aminotransferase | 18.8 International units per liter | Standard Deviation 3.7 |
Secondary
Part 1: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN)- Substance P Only at Challenge Visit 1 (Day 1)
Blood samples were collected for the analysis of clinical chemistry parameters: Calcium, glucose, potassium, sodium, and urea/BUN. 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.
Time frame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | Part 1: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN)- Substance P Only at Challenge Visit 1 (Day 1) | Calcium | 2.350 Millimoles per liter | Standard Deviation 0.091 |
| Part 1- Skin Challenges | Part 1: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN)- Substance P Only at Challenge Visit 1 (Day 1) | Glucose | 5.09 Millimoles per liter | Standard Deviation 0.457 |
| Part 1- Skin Challenges | Part 1: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN)- Substance P Only at Challenge Visit 1 (Day 1) | Potassium | 4.27 Millimoles per liter | Standard Deviation 0.265 |
| Part 1- Skin Challenges | Part 1: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN)- Substance P Only at Challenge Visit 1 (Day 1) | Sodium | 141.8 Millimoles per liter | Standard Deviation 1.86 |
| Part 1- Skin Challenges | Part 1: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN)- Substance P Only at Challenge Visit 1 (Day 1) | Urea/BUN | 4.04 Millimoles per liter | Standard Deviation 0.979 |
Secondary
Part 1: Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine- Substance P Only at Challenge Visit 1 (Day 1)
Blood samples were collected for the analysis of clinical chemistry parameters: Total Bilirubin and creatinine. 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.
Time frame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | Part 1: Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine- Substance P Only at Challenge Visit 1 (Day 1) | Total bilirubin | 11.6 Micromoles per liter | Standard Deviation 3.5 |
| Part 1- Skin Challenges | Part 1: Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine- Substance P Only at Challenge Visit 1 (Day 1) | Creatinine | 60.3 Micromoles per liter | Standard Deviation 10.54 |
Secondary
Part 1: Change From Baseline in Clinical Chemistry Parameter: Total Protein- Substance P Only at Challenge Visit 1 (Day 1)
Blood samples were collected for the analysis of clinical chemistry parameter: Total protein. 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.
Time frame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 1: Change From Baseline in Clinical Chemistry Parameter: Total Protein- Substance P Only at Challenge Visit 1 (Day 1) | 69.4 Grams per liter | Standard Deviation 3.97 |
Secondary
Part 1: Change From Baseline in Hematology Parameter: Hematocrit- Substance P Only at Challenge Visit 1 (Day 1)
Blood samples were collected for the analysis of hematology parameter: Hematocrit. 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.
Time frame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 1: Change From Baseline in Hematology Parameter: Hematocrit- Substance P Only at Challenge Visit 1 (Day 1) | 0.4117 Proportion of red blood cells in blood | Standard Deviation 0.02807 |
Secondary
Part 1: Change From Baseline in Hematology Parameter: Hemoglobin- Substance P Only at Challenge Visit 1 (Day 1)
Blood samples were collected for the analysis of hematology parameter: Hemoglobin. 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.
Time frame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 1: Change From Baseline in Hematology Parameter: Hemoglobin- Substance P Only at Challenge Visit 1 (Day 1) | 140.186580 Grams per liter | Standard Deviation 11.4507222 |
Secondary
Part 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin- Substance P Only at Challenge Visit 1 (Day 1)
Blood samples were collected for the analysis of hematology parameter: Mean corpuscle hemoglobin. 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.
Time frame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin- Substance P Only at Challenge Visit 1 (Day 1) | 30.203673 Picograms | Standard Deviation 1.0991155 |
Secondary
Part 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume- Substance P Only at Challenge Visit 1 (Day 1)
Blood samples were collected for the analysis of hematology parameter: Mean corpuscle volume. 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.
Time frame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume- Substance P Only at Challenge Visit 1 (Day 1) | 89.0 Femtoliters | Standard Deviation 4.09 |
Secondary
Part 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count- Substance P Only at Challenge Visit 1 (Day 1)
Blood samples were collected for the analysis of hematology parameter: Red 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.
Time frame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count- Substance P Only at Challenge Visit 1 (Day 1) | 4.652 Trillion cells per liter | Standard Deviation 0.5003 |
Secondary
Part 1: Change From Baseline in Hematology Parameter: Reticulocyte- Substance P Only at Challenge Visit 1 (Day 1)
Blood samples were collected for the analysis of hematology parameter: Reticulocyte. 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.
Time frame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 1: Change From Baseline in Hematology Parameter: Reticulocyte- Substance P Only at Challenge Visit 1 (Day 1) | 0.01197 Percentage of reticulocytes | Standard Deviation 0.00216 |
Secondary
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.
Time frame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | 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) | Basophils | 0.041 Giga cells per liter | Standard Deviation 0.0215 |
| Part 1- Skin Challenges | 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) | Eosinophils | 0.112 Giga cells per liter | Standard Deviation 0.1402 |
| Part 1- Skin Challenges | 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) | Lymphocytes | 1.818 Giga cells per liter | Standard Deviation 0.3138 |
| Part 1- Skin Challenges | 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) | Monocytes | 0.413 Giga cells per liter | Standard Deviation 0.1055 |
| Part 1- Skin Challenges | 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) | Total neutrophil count | 3.141 Giga cells per liter | Standard Deviation 1.1766 |
| Part 1- Skin Challenges | 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) | Platelet count | 256.8 Giga cells per liter | Standard Deviation 56.77 |
| Part 1- Skin Challenges | 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) | White blood cell count | 5.526 Giga cells per liter | Standard Deviation 1.3657 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed. Zeros reported reflect measured data derived during analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | 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) | Saline | 0.0000 Millimeter square*minutes | Standard Deviation 0 |
| Part 1- Skin Challenges | 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) | Histamine | 47977.8047 Millimeter square*minutes | Standard Deviation 35779.56892 |
| Part 1- Skin Challenges | 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) | SP 5 pmol | 8232.5351 Millimeter square*minutes | Standard Deviation 10307.53738 |
| Part 1- Skin Challenges | 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) | SP 15 pmol | 26562.8609 Millimeter square*minutes | Standard Deviation 22150.495 |
| Part 1- Skin Challenges | 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) | SP 50 pmol | 53505.6580 Millimeter square*minutes | Standard Deviation 31081.10933 |
| Part 1- Skin Challenges | 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) | SP 150 pmol | 54407.2697 Millimeter square*minutes | Standard Deviation 34805.98795 |
| Part 1- Skin Challenges | 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) | SP 500 pmol | 64978.5132 Millimeter square*minutes | Standard Deviation 67350.94024 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed. Zeros reported reflect measured data derived during analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | 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) | Saline | 0.0000 Millimeter square | Standard Deviation 0 |
| Part 1- Skin Challenges | 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) | Histamine | 1209.6224 Millimeter square | Standard Deviation 604.47133 |
| Part 1- Skin Challenges | 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) | SP 5 pmol | 619.6359 Millimeter square | Standard Deviation 940.2608 |
| Part 1- Skin Challenges | 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) | SP 15 pmol | 1422.8103 Millimeter square | Standard Deviation 763.79695 |
| Part 1- Skin Challenges | 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) | SP 50 pmol | 2240.1860 Millimeter square | Standard Deviation 971.83781 |
| Part 1- Skin Challenges | 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) | SP 150 pmol | 2282.5890 Millimeter square | Standard Deviation 1149.0319 |
| Part 1- Skin Challenges | 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) | SP 500 pmol | 2383.3822 Millimeter square | Standard Deviation 1590.27531 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | 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) | Saline | 15.2152 Millimeter square | Standard Deviation 8.97791 |
| Part 1- Skin Challenges | 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) | Histamine | 44.5782 Millimeter square | Standard Deviation 16.73404 |
| Part 1- Skin Challenges | 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) | SP 5 pmol | 42.4284 Millimeter square | Standard Deviation 20.26132 |
| Part 1- Skin Challenges | 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) | SP 15 pmol | 82.7571 Millimeter square | Standard Deviation 41.76154 |
| Part 1- Skin Challenges | 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) | SP 50 pmol | 99.8398 Millimeter square | Standard Deviation 48.06381 |
| Part 1- Skin Challenges | 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) | SP 150 pmol | 126.1186 Millimeter square | Standard Deviation 55.2804 |
| Part 1- Skin Challenges | 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) | SP 500 pmol | 194.0748 Millimeter square | Standard Deviation 178.88175 |
Secondary
Part 1: Number of Participants With Clinically Significant Abnormal 12-lead Electrocardiogram (ECG) Findings- Substance P Only at Challenge Visit 1 (Day 1)
12-lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and corrected QT (QTc) intervals and calculated heart rate. Data for abnormal, clinically significant (CS) ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time frame: At Day 1 (Visit 1)
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1- Skin Challenges | Part 1: Number of Participants With Clinically Significant Abnormal 12-lead Electrocardiogram (ECG) Findings- Substance P Only at Challenge Visit 1 (Day 1) | 0 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Skin Challenges | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)- Substance P Only | Non-serious AEs | 1 Participants |
| Part 1- Skin Challenges | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)- Substance P Only | SAEs | 0 Participants |
Secondary
Part 1: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1)
Urine samples were collected for the analysis of urinalysis parameters: Occult blood, glucose, ketones and protein by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters indicate proportional concentrations in the urine sample. Number of participants with abnormal results were reported as 'Any increase' if there was any increase in their urine concentrations compared to Baseline. Participants whose value was unchanged or whose value was decreased, were recorded in the 'No change/Decreased' category. Baseline value is defined as the latest non-missing pre-first control challenge assessment value at challenge visit 1, including those from unscheduled visits.
Time frame: At Day 1 (Visit 1)
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Skin Challenges | Part 1: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1) | Occult blood: No change/decreased | 8 Participants |
| Part 1- Skin Challenges | Part 1: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1) | Occult blood: Any increase | 1 Participants |
| Part 1- Skin Challenges | Part 1: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1) | Glucose: No change/decreased | 9 Participants |
| Part 1- Skin Challenges | Part 1: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1) | Glucose: Any increase | 0 Participants |
| Part 1- Skin Challenges | Part 1: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1) | Ketones No change/decreased | 9 Participants |
| Part 1- Skin Challenges | Part 1: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1) | Ketones: Any increase | 0 Participants |
| Part 1- Skin Challenges | Part 1: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1) | Protein: No change/decreased | 9 Participants |
| Part 1- Skin Challenges | Part 1: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1) | Protein: Any increase | 0 Participants |
Secondary
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)
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Skin Challenges | 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) | SBP: To High | 0 Participants |
| Part 1- Skin Challenges | 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) | DBP: To High | 0 Participants |
| Part 1- Skin Challenges | 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) | SBP: To low | 0 Participants |
| Part 1- Skin Challenges | 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) | SBP: To within range or no Change | 9 Participants |
| Part 1- Skin Challenges | 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) | DBP: To low | 0 Participants |
| Part 1- Skin Challenges | 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) | DBP: To within range or no Change | 9 Participants |
| Part 1- Skin Challenges | 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) | Heart rate: To low | 0 Participants |
| Part 1- Skin Challenges | 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) | Heart rate: To within range or no Change | 9 Participants |
| Part 1- Skin Challenges | 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) | Heart rate: To High | 0 Participants |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1- Skin Challenges | 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) | Saline | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | Histamine | 89.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 5 pmol | 20.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 15 pmol | 42.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 50 pmol | 59.5 Minutes |
| Part 1- Skin Challenges | 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) | SP 150 pmol | 60.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 500 pmol | 61.0 Minutes |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1- Skin Challenges | 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) | Saline | 39.0 Minutes |
| Part 1- Skin Challenges | 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) | Histamine | 90.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 5 pmol | 62.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 15 pmol | 120.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 50 pmol | 74.5 Minutes |
| Part 1- Skin Challenges | 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) | SP 150 pmol | 75.5 Minutes |
| Part 1- Skin Challenges | 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) | SP 500 pmol | 104.5 Minutes |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1- Skin Challenges | 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) | Saline | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | Histamine | 15.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 5 pmol | 10.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 15 pmol | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 50 pmol | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 150 pmol | 6.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 500 pmol | 5.0 Minutes |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1- Skin Challenges | 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) | Saline | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | Histamine | 20.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 5 pmol | 20.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 15 pmol | 20.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 50 pmol | 17.5 Minutes |
| Part 1- Skin Challenges | 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) | SP 150 pmol | 20.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 500 pmol | 20.0 Minutes |
Secondary
Part 2: Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase and Aspartate Aminotransferase- Substance P Only at Challenge Visit 2 (Week 2)
Blood samples were collected for the analysis of clinical chemistry parameters: Alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. 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. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase and Aspartate Aminotransferase- Substance P Only at Challenge Visit 2 (Week 2) | Alkaline phosphatase | 72.4 International units per liter | Standard Deviation 30.54 |
| Part 1- Skin Challenges | Part 2: Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase and Aspartate Aminotransferase- Substance P Only at Challenge Visit 2 (Week 2) | Alanine aminotransferase | 19.7 International units per liter | Standard Deviation 7.38 |
| Part 1- Skin Challenges | Part 2: Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase and Aspartate Aminotransferase- Substance P Only at Challenge Visit 2 (Week 2) | Aspartate aminotransferase | 21.1 International units per liter | Standard Deviation 5.85 |
Secondary
Part 2: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/BUN- Substance P Only at Challenge Visit 2 (Week 2)
Blood samples were collected for the analysis of clinical chemistry parameters: Calcium, glucose, potassium, sodium, and urea/BUN. 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. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/BUN- Substance P Only at Challenge Visit 2 (Week 2) | Calcium | 2.346 Millimoles per liter | Standard Deviation 0.1074 |
| Part 1- Skin Challenges | Part 2: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/BUN- Substance P Only at Challenge Visit 2 (Week 2) | Glucose | 4.89 Millimoles per liter | Standard Deviation 0.713 |
| Part 1- Skin Challenges | Part 2: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/BUN- Substance P Only at Challenge Visit 2 (Week 2) | Potassium | 4.19 Millimoles per liter | Standard Deviation 0.315 |
| Part 1- Skin Challenges | Part 2: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/BUN- Substance P Only at Challenge Visit 2 (Week 2) | Sodium | 141.1 Millimoles per liter | Standard Deviation 2.38 |
| Part 1- Skin Challenges | Part 2: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/BUN- Substance P Only at Challenge Visit 2 (Week 2) | Urea/BUN | 4.38 Millimoles per liter | Standard Deviation 1.614 |
Secondary
Part 2: Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine- Substance P Only at Challenge Visit 2 (Week 2)
Blood samples were collected for the analysis of clinical chemistry parameters: Total bilirubin and creatinine. 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. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine- Substance P Only at Challenge Visit 2 (Week 2) | Total bilirubin | 6.7 Micromoles per liter | Standard Deviation 2.8 |
| Part 1- Skin Challenges | Part 2: Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine- Substance P Only at Challenge Visit 2 (Week 2) | Creatinine | 66.9 Micromoles per liter | Standard Deviation 13.67 |
Secondary
Part 2: Change From Baseline in Clinical Chemistry Parameter: Total Protein- Substance P Only at Challenge Visit 2 (Week 2)
Blood samples were collected for the analysis of clinical chemistry parameter: Total protein. 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. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Change From Baseline in Clinical Chemistry Parameter: Total Protein- Substance P Only at Challenge Visit 2 (Week 2) | 68.8 Grams per liter | Standard Deviation 3.72 |
Secondary
Part 2: Change From Baseline in Hematology Parameter: Hematocrit- Substance P Only at Challenge Visit 2 (Week 2)
Blood samples were collected for the analysis of hematology parameter: Hematocrit. 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. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Change From Baseline in Hematology Parameter: Hematocrit- Substance P Only at Challenge Visit 2 (Week 2) | 0.3929 Proportion of red blood cells in blood | Standard Deviation 0.02349 |
Secondary
Part 2: Change From Baseline in Hematology Parameter: Hemoglobin- Substance P Only at Challenge Visit 2 (Week 2)
Blood samples were collected for the analysis of hematology parameter: Hemoglobin. 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. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Change From Baseline in Hematology Parameter: Hemoglobin- Substance P Only at Challenge Visit 2 (Week 2) | 133.821787 Grams per liter | Standard Deviation 8.9711806 |
Secondary
Part 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin- Substance P Only at Challenge Visit 2 (Week 2)
Blood samples were collected for the analysis of hematology parameter: Mean corpuscle hemoglobin. 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. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin- Substance P Only at Challenge Visit 2 (Week 2) | 30.204568 Picograms | Standard Deviation 1.6675822 |
Secondary
Part 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume- Substance P Only at Challenge Visit 2 (Week 2)
Blood samples were collected for the analysis of hematology parameter: Mean corpuscle volume. 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. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume- Substance P Only at Challenge Visit 2 (Week 2) | 88.7 Femtoliters | Standard Deviation 2.92 |
Secondary
Part 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count- Substance P Only at Challenge Visit 2 (Week 2)
Blood samples were collected for the analysis of hematology parameter: Red blood cell count. 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. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count- Substance P Only at Challenge Visit 2 (Week 2) | 4.440 Trillion cells per liter | Standard Deviation 0.3345 |
Secondary
Part 2: Change From Baseline in Hematology Parameter: Reticulocyte- Substance P Only at Challenge Visit 2 (Week 2)
Blood samples were collected for the analysis of hematology parameter: Reticulocyte. 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. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Change From Baseline in Hematology Parameter: Reticulocyte- Substance P Only at Challenge Visit 2 (Week 2) | 0.01482 Percentage of reticulocytes | Standard Deviation 0.004017 |
Secondary
Part 2: 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 2 (Week 2)
Blood samples were collected for the analysis of hematology parameters: Basophils, eosinophils, lymphocytes, monocytes, total neutrophil count, platelet count and white blood cell count. 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. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | Part 2: 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 2 (Week 2) | Basophils | 0.045 Giga cells per liter | Standard Deviation 0.0235 |
| Part 1- Skin Challenges | Part 2: 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 2 (Week 2) | Eosinophils | 0.308 Giga cells per liter | Standard Deviation 0.3889 |
| Part 1- Skin Challenges | Part 2: 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 2 (Week 2) | Lymphocytes | 2.016 Giga cells per liter | Standard Deviation 0.5291 |
| Part 1- Skin Challenges | Part 2: 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 2 (Week 2) | Monocytes | 0.490 Giga cells per liter | Standard Deviation 0.1649 |
| Part 1- Skin Challenges | Part 2: 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 2 (Week 2) | Total neutrophil count | 3.788 Giga cells per liter | Standard Deviation 1.3756 |
| Part 1- Skin Challenges | Part 2: 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 2 (Week 2) | Platelet count | 244.5 Giga cells per liter | Standard Deviation 54.47 |
| Part 1- Skin Challenges | Part 2: 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 2 (Week 2) | White blood cell count | 6.646 Giga cells per liter | Standard Deviation 1.7007 |
Secondary
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)
Population: Safety Population. Zeros reported reflect measured data derived during analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | 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) | Saline : 2 hours post-challenge on Day 1 | 0.0000 Millimeter square*minutes | Standard Deviation 0 |
| Part 1- Skin Challenges | 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) | Saline: 2 hours post-challenge at Week 2 | 0.0000 Millimeter square*minutes | Standard Deviation 0 |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge on Day 1 | 42825.0421 Millimeter square*minutes | Standard Deviation 31599.99246 |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge at Week 2 | 50717.6974 Millimeter square*minutes | Standard Deviation 35294.02927 |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge on Day 1 | 20515.8733 Millimeter square*minutes | Standard Deviation 17779.8445 |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge at Week 2 | 30689.5773 Millimeter square*minutes | Standard Deviation 29415.10538 |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge on Day 1 | 48796.3715 Millimeter square*minutes | Standard Deviation 31253.62644 |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge at Week 2 | 52359.5705 Millimeter square*minutes | Standard Deviation 34531.05693 |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge on Day 1 | 68798.6958 Millimeter square*minutes | Standard Deviation 36263.19533 |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge at Week 2 | 81245.6716 Millimeter square*minutes | Standard Deviation 50591.14135 |
| Part 1- Skin Challenges | 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) | SP 150 pmol:2 hours post-challenge on Day 1 | 76360.0164 Millimeter square*minutes | Standard Deviation 32955.71419 |
| Part 1- Skin Challenges | 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) | SP 150 pmol: 2 hours post-challenge at Week 2 | 77243.2496 Millimeter square*minutes | Standard Deviation 37747.18154 |
Secondary
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)
Population: Safety Population. Zeros reported reflect measured data derived during analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | 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) | Saline : 2 hours post-challenge on Day 1 | 0.0000 Millimeter square | Standard Deviation 0 |
| Part 1- Skin Challenges | 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) | Saline: 2 hours post-challenge at Week 2 | 0.0000 Millimeter square | Standard Deviation 0 |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge on Day 1 | 1110.0748 Millimeter square | Standard Deviation 514.76131 |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge at Week 2 | 1392.6911 Millimeter square | Standard Deviation 671.10955 |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge on Day 1 | 1035.4156 Millimeter square | Standard Deviation 572.41049 |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge at Week 2 | 1398.2891 Millimeter square | Standard Deviation 1007.58015 |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge on Day 1 | 1892.5393 Millimeter square | Standard Deviation 791.1082 |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge at Week 2 | 1956.0858 Millimeter square | Standard Deviation 1018.31529 |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge on Day 1 | 2229.9920 Millimeter square | Standard Deviation 772.48097 |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge at Week 2 | 2575.5958 Millimeter square | Standard Deviation 1627.22854 |
| Part 1- Skin Challenges | 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) | SP 150 pmol:2 hours post-challenge on Day 1 | 2058.1909 Millimeter square | Standard Deviation 660.32625 |
| Part 1- Skin Challenges | 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) | SP 150 pmol: 2 hours post-challenge at Week 2 | 2281.9739 Millimeter square | Standard Deviation 853.10184 |
Secondary
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)
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Skin Challenges | 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) | Saline : 2 hours post-challenge on Day 1 | 16.6335 Millimeter square | Standard Deviation 11.36559 |
| Part 1- Skin Challenges | 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) | Saline: 2 hours post-challenge at Week 2 | 21.7610 Millimeter square | Standard Deviation 12.79723 |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge on Day 1 | 53.1929 Millimeter square | Standard Deviation 26.57857 |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge at Week 2 | 52.8665 Millimeter square | Standard Deviation 16.31003 |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge on Day 1 | 85.8111 Millimeter square | Standard Deviation 23.45193 |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge at Week 2 | 92.1595 Millimeter square | Standard Deviation 24.44909 |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge on Day 1 | 112.9690 Millimeter square | Standard Deviation 30.79242 |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge at Week 2 | 113.0940 Millimeter square | Standard Deviation 26.92327 |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge on Day 1 | 134.6049 Millimeter square | Standard Deviation 39.38378 |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge at Week 2 | 151.1447 Millimeter square | Standard Deviation 39.31424 |
| Part 1- Skin Challenges | 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) | SP 150 pmol:2 hours post-challenge on Day 1 | 148.8571 Millimeter square | Standard Deviation 47.72791 |
| Part 1- Skin Challenges | 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) | SP 150 pmol: 2 hours post-challenge at Week 2 | 153.0084 Millimeter square | Standard Deviation 39.8131 |
Secondary
Part 2: Number of Participants With Clinically Significant Abnormal 12-lead ECG Findings- Substance P Only at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)
12-lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and QTc intervals and calculated heart rate. Data for abnormal, CS ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time frame: At Day 1 (Visit 1) and Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Number of Participants With Clinically Significant Abnormal 12-lead ECG Findings- Substance P Only at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2) | Day 1 | 0 Participants |
| Part 1- Skin Challenges | Part 2: Number of Participants With Clinically Significant Abnormal 12-lead ECG Findings- Substance P Only at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2) | Week 2 | 0 Participants |
Secondary
Part 2: Number of Participants With Non-serious AEs and 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 3 weeks
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Number of Participants With Non-serious AEs and SAEs- Substance P Only | Non-serious AEs | 2 Participants |
| Part 1- Skin Challenges | Part 2: Number of Participants With Non-serious AEs and SAEs- Substance P Only | SAEs | 0 Participants |
Secondary
Part 2: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 2 (Week 2)
Urine samples were collected for the analysis of urinalysis parameters: Occult blood, glucose, ketones and protein by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters indicate proportional concentrations in the urine sample. Number of participants with abnormal results were reported as 'Any increase' if there was any increase in their urine concentrations compared to Baseline. Participants whose value was unchanged or whose value was decreased, were recorded in the 'No change/Decreased' category. 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.
Time frame: At Week 2 (Visit 2)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Skin Challenges | Part 2: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 2 (Week 2) | Occult blood: No change/decreased | 20 Participants |
| Part 1- Skin Challenges | Part 2: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 2 (Week 2) | Occult blood: Any increase | 0 Participants |
| Part 1- Skin Challenges | Part 2: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 2 (Week 2) | Glucose: No change/decreased | 20 Participants |
| Part 1- Skin Challenges | Part 2: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 2 (Week 2) | Glucose: Any increase | 0 Participants |
| Part 1- Skin Challenges | Part 2: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 2 (Week 2) | Ketones No change/decreased | 20 Participants |
| Part 1- Skin Challenges | Part 2: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 2 (Week 2) | Ketones: Any increase | 0 Participants |
| Part 1- Skin Challenges | Part 2: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 2 (Week 2) | Protein: No change/decreased | 20 Participants |
| Part 1- Skin Challenges | Part 2: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 2 (Week 2) | Protein: Any increase | 0 Participants |
Secondary
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)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Skin Challenges | 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) | SBP: To low, Day 1 | 0 Participants |
| Part 1- Skin Challenges | 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) | SBP: To within range or no Change, Day 1 | 20 Participants |
| Part 1- Skin Challenges | 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) | SBP: To High, Day 1 | 0 Participants |
| Part 1- Skin Challenges | 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) | SBP: To low, Week 2 | 0 Participants |
| Part 1- Skin Challenges | 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) | SBP: To within range or no Change, Week 2 | 20 Participants |
| Part 1- Skin Challenges | 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) | SBP: To High, Week 2 | 0 Participants |
| Part 1- Skin Challenges | 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) | DBP: To low, Day 1 | 0 Participants |
| Part 1- Skin Challenges | 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) | DBP: To within range or no Change, Day 1 | 20 Participants |
| Part 1- Skin Challenges | 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) | DBP: To High, Day 1 | 0 Participants |
| Part 1- Skin Challenges | 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) | DBP: To low, Week 2 | 0 Participants |
| Part 1- Skin Challenges | 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) | DBP: To within range or no Change, Week 2 | 20 Participants |
| Part 1- Skin Challenges | 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) | DBP: To High, Week 2 | 0 Participants |
| Part 1- Skin Challenges | 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) | Heart rate: To low, Day 1 | 0 Participants |
| Part 1- Skin Challenges | 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) | Heart rate: To within range or no Change, Day 1 | 20 Participants |
| Part 1- Skin Challenges | 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) | Heart rate: To High, Day 1 | 0 Participants |
| Part 1- Skin Challenges | 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) | Heart rate: To low, Week 2 | 0 Participants |
| Part 1- Skin Challenges | 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) | Heart rate: To within range or no Change,Week 2 | 20 Participants |
| Part 1- Skin Challenges | 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) | Heart rate: To High, Week 2 | 0 Participants |
Secondary
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1- Skin Challenges | 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) | SP 150 pmol:2 hours post-challenge on Day 1 | 90.0 Minutes |
| Part 1- Skin Challenges | 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) | Saline : 2 hours post-challenge on Day 1 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | Saline: 2 hours post-challenge at Week 2 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge on Day 1 | 75.5 Minutes |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge at Week 2 | 76.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge on Day 1 | 40.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge at Week 2 | 39.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge on Day 1 | 59.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge at Week 2 | 59.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge on Day 1 | 61.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge at Week 2 | 60.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 150 pmol: 2 hours post-challenge at Week 2 | 88.0 Minutes |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1- Skin Challenges | 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) | Saline : 2 hours post-challenge on Day 1 | 16.0 Minutes |
| Part 1- Skin Challenges | 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) | Saline: 2 hours post-challenge at Week 2 | 20.0 Minutes |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge on Day 1 | 90.5 Minutes |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge at Week 2 | 90.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge on Day 1 | 89.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge at Week 2 | 61.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge on Day 1 | 90.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge at Week 2 | 88.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge on Day 1 | 90.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge at Week 2 | 90.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 150 pmol:2 hours post-challenge on Day 1 | 104.5 Minutes |
| Part 1- Skin Challenges | 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) | SP 150 pmol: 2 hours post-challenge at Week 2 | 90.0 Minutes |
Secondary
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1- Skin Challenges | 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) | SP 150 pmol: 2 hours post-challenge at Week 2 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 150 pmol:2 hours post-challenge on Day 1 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | Saline : 2 hours post-challenge on Day 1 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | Saline: 2 hours post-challenge at Week 2 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge on Day 1 | 11.0 Minutes |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge at Week 2 | 6.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge on Day 1 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge at Week 2 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge on Day 1 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge at Week 2 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge on Day 1 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge at Week 2 | 5.5 Minutes |
Secondary
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge at Week 2 | 24.5 Minutes |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge on Day 1 | 18.5 Minutes |
| Part 1- Skin Challenges | 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) | Saline : 2 hours post-challenge on Day 1 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | Saline: 2 hours post-challenge at Week 2 | 5.0 Minutes |
| Part 1- Skin Challenges | 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) | Histamine: 2 hours post-challenge on Day 1 | 30.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 5 pmol: 2 hours post-challenge at Week 2 | 19.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge on Day 1 | 19.5 Minutes |
| Part 1- Skin Challenges | 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) | SP 15 pmol: 2 hours post-challenge at Week 2 | 18.5 Minutes |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge on Day 1 | 23.5 Minutes |
| Part 1- Skin Challenges | 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) | SP 50 pmol: 2 hours post-challenge at Week 2 | 25.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 150 pmol:2 hours post-challenge on Day 1 | 28.0 Minutes |
| Part 1- Skin Challenges | 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) | SP 150 pmol: 2 hours post-challenge at Week 2 | 27.5 Minutes |