An open label, single centre, enabling study to investigate the optimum method for use of intradermal Substance P as a challenge agent in healthy participants
- Conditions
- N.a.10014982
- Registration Number
- NL-OMON49281
- Lead Sponsor
- GlaxoSmithKline Research & Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 32
Participants are eligible to be included in the study only if all of the
following criteria apply:
Age
1. Participant must be 18 to 50 years of age inclusive, at the time of signing
the informed consent.
Type of Participant and Disease Characteristics
2. Participants who are overtly healthy as determined by medical evaluation
including medical history, physical examination, laboratory tests, ECGs and
vital signs.
3. Participants who responded positive to histamine skin prick test and
negative to saline injection at screening.
4. Participants with Fitzpatrick skin type I-II (Caucasian).
Weight
5. Body weight *50 kg and body mass index (BMI) within the range 19*29.9 kg/m2
(inclusive).
Sex
Sex and Contraceptive/Barrier Requirements
6. Male participants are eligible to participate in the study
- A female participant is eligible to participate if she is not pregnant or
breastfeeding, and one of the following conditions applies:
o Is a woman of non-childbearing potential (WONCBP) as defined in Section 10.4
of the protocol: Contraceptive and Barrier Guidance.
OR
o Is a WOCBP and using a contraceptive method that is highly effective, with a
failure rate of <1%, as described in Section 10.4 of the protocol during the
study
intervention period. The investigator should evaluate potential for
contraceptive method failure (e.g., noncompliance, recently initiated) in
relationship to the first challenge.
- A sensitive pregnancy test is required to be negative on the day of each
challenge.
This pregnancy test is able to detect a pregnancy near the threshold of
implantation, correlating with the earliest point of potential exposure. Due to
the short half-life of the interventions, a negative highly sensitive pregnancy
test as scheduled in the protocol mitigates the risk of pregnancy exposure
because exposure will be completely gone even with a worst case but unlikely
scenario of conception occurring near the time of dosing. See Protocol Section
8.2.5 Pregnancy Testing
- If a urine test cannot be confirmed as negative (e.g., an ambiguous result),
a serum pregnancy test is required. In such cases, the participant must be
excluded from participation if the serum pregnancy result is positive.
- Additional requirements for pregnancy testing during and after study
intervention is located in Protocol Section 8.2.5 .
- The investigator is responsible for review of medical history, menstrual
history, and recent sexual activity to decrease the risk for inclusion of a
woman with an early undetected pregnancy
Informed Consent
7. Capable of giving signed informed consent as described in Appendix 1 of the
protocol which includes compliance with the requirements and restrictions
listed in the informed consent form (ICF) and in this protocol.
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Significant history of or current, cardiovascular (including hypotension,
severe hypertension, vasomotor instability), respiratory (including asthma),
renal, gastrointestinal, endocrine, haematological, infectious or neurological
disorders constituting a risk when taking part in the study or interfering with
the interpretation of data.
2. History or presence of significant skin disorder (such as but not limited to
chronic urticaria, atopic dermatitis, severe eczema, psoriasis or skin cancer).
3. History of risk for or actual experience of complications from skin biopsy
including excess bleeding, infection, or scarring/keloid formation.
4. Abnormal blood pressure as determined by the investigator.
5. Alanine transaminase (ALT) >1.5x upper limit of normal (ULN).
6. Total bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if total
bilirubin is fractionated and direct bilirubin <35%).
7. Current or chronic history of liver disease, or known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic
gallstones).
8. QT interval corrected for heart rate according to Fridericia*s formula
(QTcF) >450 msec, based on the mean of triplicate ECGs .
NOTE: The QTc is the QT interval corrected for heart rate according to
Fridericia*s formula (QTcF).
Prior/Concomitant Therapy
9. 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.
10. 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.
11. 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 GSK
Medical Monitor, the medication will not constitute a risk when taking the
study intervention or interfere with the interpretation of data.
Prior/Concurrent Clinical Study Experience
12. Participation in the study would result in loss of blood or blood products
in excess of 500 mL within 3 months.
13. Current enrolment in any clinical study involving an investigational study
intervention or any other type of medical research.
14. Current enrolment or past participation in this study.
Diagnostic assessments
15. Presence of Hepatitis B surface antigen (HBsAg) or hepatitis B core
antibody (HbcAb) at screening or within 3 months before the first challenge day.
16. Positive Hepatitis C antibody test result at screening or within 3 months
before the first challenge day.
NOTE: Subjects with positive Hepatitis C antibody due to prior resolved disease
can be enrolled, only if a confirmatory negative Hepatitis C RNA test is
obtained
17. Positive Hepatitis C RNA test result at screening or within 3 months before
the first challenge day.
NOTE: Test is optional and
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Part 1<br /><br>- Wheal response during the 2 h postchallenge period area under the curve (AUC)<br /><br>at each concentration of SP<br /><br><br /><br>Part 2<br /><br>- Wheal response during the 2 h postchallenge period (AUC) at each<br /><br>concentration of SP across 2 challenge days</p><br>
- Secondary Outcome Measures
Name Time Method