N/A
N=12
Substance P Challenge in Healthy Participants
Skin Diseases
Bottom Line
View on ClinicalTrials.gov: NCT04676763 ↗Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Feb 2024
Primary outcome: 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) — 155.2379; 2151.2320; 2749.0997; 5727.2220 Millimeter square*minutes
Study Design & Population
- Study type
- Interventional
- Phase
- N/A
- Interventions
- Substance P (Drug); Normal Saline (Drug); Histamine (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Jul 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| 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) |
155.2379; 2151.2320; 2749.0997; 5727.2220; 7111.5570; 8295.6310 | — |
| 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) |
157.9157; 216.5196; 2617.3622; 2486.9477; 4534.4513; 4563.5113 | — |
| 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) |
15.2152; 44.5782; 42.4284; 82.7571; 99.8398; 126.1186 | — |
| 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) |
16.6335; 21.7610; 53.1929; 52.8665; 85.8111; 92.1595 | — |
| 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) |
5.0; 20.0; 20.0; 20.0; 17.5; 20.0 | — |
| 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) |
5.0; 5.0; 30.0; 24.5; 18.5; 19.0 | — |
| 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) |
39.0; 90.0; 62.0; 120.0; 74.5; 75.5 | — |
| 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) |
16.0; 20.0; 90.5; 90.0; 89.0; 61.0 | — |
| 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) |
0.0000; 47977.8047; 8232.5351; 26562.8609; 53505.6580; 54407.2697 | — |
| 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) |
0.0000; 0.0000; 42825.0421; 50717.6974; 20515.8733; 30689.5773 | — |
| 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) |
0.0000; 1209.6224; 619.6359; 1422.8103; 2240.1860; 2282.5890 | — |
| 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) |
0.0000; 0.0000; 1110.0748; 1392.6911; 1035.4156; 1398.2891 | — |
| 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) |
5.0; 15.0; 10.0; 5.0; 5.0; 6.0 | — |
| 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) |
5.0; 5.0; 11.0; 6.0; 5.0; 5.0 | — |
| 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) |
5.0; 89.0; 20.0; 42.0; 59.5; 60.0 | — |
| 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) |
5.0; 5.0; 75.5; 76.0; 40.0; 39.0 | — |
| SECONDARY Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)- Substance P Only |
1; 0 | — |
| SECONDARY Part 2: Number of Participants With Non-serious AEs and SAEs- Substance P Only |
2; 0 | — |
| 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) |
0; 9; 0; 0; 9; 0 | — |
| 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) |
0; 20; 0; 0; 20; 0 | — |
| 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) |
0.041; 0.112; 1.818; 0.413; 3.141; 256.8 | — |
| 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) |
0.045; 0.308; 2.016; 0.490; 3.788; 244.5 | — |
| SECONDARY Part 1: Change From Baseline in Hematology Parameter: Hemoglobin- Substance P Only at Challenge Visit 1 (Day 1) |
140.186580 | — |
| SECONDARY Part 2: Change From Baseline in Hematology Parameter: Hemoglobin- Substance P Only at Challenge Visit 2 (Week 2) |
133.821787 | — |
| SECONDARY Part 1: Change From Baseline in Hematology Parameter: Hematocrit- Substance P Only at Challenge Visit 1 (Day 1) |
0.4117 | — |
| SECONDARY Part 2: Change From Baseline in Hematology Parameter: Hematocrit- Substance P Only at Challenge Visit 2 (Week 2) |
0.3929 | — |
| SECONDARY Part 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin- Substance P Only at Challenge Visit 1 (Day 1) |
30.203673 | — |
| SECONDARY Part 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin- Substance P Only at Challenge Visit 2 (Week 2) |
30.204568 | — |
| SECONDARY Part 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume- Substance P Only at Challenge Visit 1 (Day 1) |
89.0 | — |
| SECONDARY Part 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume- Substance P Only at Challenge Visit 2 (Week 2) |
88.7 | — |
| SECONDARY Part 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count- Substance P Only at Challenge Visit 1 (Day 1) |
4.652 | — |
| SECONDARY Part 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count- Substance P Only at Challenge Visit 2 (Week 2) |
4.440 | — |
| SECONDARY Part 1: Change From Baseline in Hematology Parameter: Reticulocyte- Substance P Only at Challenge Visit 1 (Day 1) |
0.01197 | — |
| SECONDARY Part 2: Change From Baseline in Hematology Parameter: Reticulocyte- Substance P Only at Challenge Visit 2 (Week 2) |
0.01482 | — |
| 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) |
71.1; 19.0; 18.8 | — |
| 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) |
72.4; 19.7; 21.1 | — |
| SECONDARY Part 1: Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine- Substance P Only at Challenge Visit 1 (Day 1) |
11.6; 60.3 | — |
| SECONDARY Part 2: Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine- Substance P Only at Challenge Visit 2 (Week 2) |
6.7; 66.9 | — |
| 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) |
2.350; 5.09; 4.27; 141.8; 4.04 | — |
| 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) |
2.346; 4.89; 4.19; 141.1; 4.38 | — |
| SECONDARY Part 1: Change From Baseline in Clinical Chemistry Parameter: Total Protein- Substance P Only at Challenge Visit 1 (Day 1) |
69.4 | — |
| SECONDARY Part 2: Change From Baseline in Clinical Chemistry Parameter: Total Protein- Substance P Only at Challenge Visit 2 (Week 2) |
68.8 | — |
| 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) |
8; 1; 9; 0; 9; 0 | — |
| 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) |
20; 0; 20; 0; 20; 0 | — |
| SECONDARY Part 1: Number of Participants With Clinically Significant Abnormal 12-lead Electrocardiogram (ECG) Findings- Substance P Only at Challenge Visit 1 (Day 1) |
— | — |
| 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) |
0; 0 | — |
Summary
The objectives of this enabling study are to characterize the wheal and flare responses over time following skin challenges with ascending concentrations of Substance P. This will be a 2-part study: Part 1 will aid in the understanding of the wheal and flare responses following Substance P. Part 2 will investigate the variability of the responses. Participants may be enrolled into Part 1 or Part 2, not both.
Eligibility Criteria
Inclusion criteria
- 18 to 50 years of age inclusive.
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, ECGs and vital signs.
- Participants who responded positive to histamine skin prick test and negative to saline injection at screening.
- Participants with Fitzpatrick skin type I-II (Caucasian).
- Body weight greater than or equal to (>=) 50 kilogram (kg) and body mass index (BMI) within the range 19-29.9 kilogram per meter square (kg/m2) (inclusive).
- Male participants are eligible to participate in the study.
- A female participant is eligible to participate if she is not pregnant or breastfeeding or using highly effective contraceptive methods. Woman of non-childbearing potential can also participate.
- A sensitive pregnancy test is required to be negative on the day of each challenge.
- Capable of giving signed informed consent.
Exclusion Criteria
- Significant history of or current, cardiovascular (including hypotension, severe hypertension, vasomotor instability), respiratory (including asthma), renal, gastrointestinal, endocrine, hematological, infectious or neurological disorders constituting a risk when taking part in the study or interfering with the interpretation of data.
- History or presence of significant skin disorder (such as but not limited to chronic urticaria, atopic dermatitis, severe eczema, psoriasis or skin cancer).
- History of risk for or actual experience of complications from skin biopsy including excess bleeding, infection, or scarring/keloid formation.
- Abnormal blood pressure as determined by the investigator.
- Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).
- Total bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if total bilirubin is fractionated and direct bilirubin 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 a
Data sourced from ClinicalTrials.gov (NCT04676763). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.