723/726 Proof of Concept Study in Allergen Challenge Chamber in Hannover

Study Overview
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Brief Summary
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This is a randomised, double-blind, placebo-controlled 4-period cross-over study to assess the efficacy and safety of repeat dose intranasal GSK1004723 (1000µg), oral GSK835726 (10mg) and cetirizine (10mg) in the environmental challenge chamber in subjects with seasonal allergic rhinitis.

Official Title
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A Randomised, Double-blind, Placebo-controlled 4-period Cross-over Study to Assess the Efficacy and Safety of Repeat Dose Intranasal GSK1004723 (1000µg), Oral GSK835726 (10mg) and Cetirizine (10mg) in the Environmental Challenge Chamber in Subjects With Seasonal Allergic Rhinitis

Conditions
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Rhinitis, Allergic, Seasonal

Intervention / Treatment
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* Drug: GSK835726 10mg
* Drug: GSK1004723 1000mcg
* Drug: Cetirizine 10mg
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is healthy apart from seasonal allergic rhinitis, as determined by a physician. Can have mild asthma. Males or female using contraceptives Aged 18 - 65 Weight 50kg+, BMI 19-32 kg/m2 Exhibit response to Challenge Chamber and skin prick test. Non-smoker Capable of giving informed consent AST and ALT<2xULN; alkaline phosphatase and bilirubin <or=1.5xULN Exclusion Criteria: No nasal structural abnornmality/polyposis, surgery, infection. any respiratory disease, other than mild asthma or seasonal allergic rhinitis participated in another clinical study within 30 days. Subject has donated a unit of blood within 1 month Use of prescription or non-prescription drugs, including vitamins and st john's wort within 7 days of trial. History of sensitivty to drug History of alcohol/drug abuse within 12 months. Positive Hepatitis B antibody test Positive HIV antibody test Risk of non-compliance with study protocol Pregnant or llactating females Perenial allergic rhinitis Administration of oral, injectable or dermal corticosteriods within 8 weeks, intranasal or inhaled within 3 weeks. Past or present disease that may affect outcome, as judge by investigator Specific Immunotherapy within 2 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GSK835726 (10mg)<br>10mg oral dose | Drug: GSK835726 10mg<br>* GSK835726 10mg tablet<br>|
| Active Comparator: GSK1004723 (1000mcg)<br>1000mcg nasal spray solution | Drug: GSK1004723 1000mcg<br>* GSK1004723 1000mcg nasal spray solution<br>|
| Active Comparator: Cetirizine 10mg<br>10mg cetirizine as active comparator | Drug: Cetirizine 10mg<br>* Cetirizine 10mg active comparator<br>|
| Placebo Comparator: placebo<br>placebo | Drug: placebo<br>* placebo to match actives<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weighted Mean TNSS (Sneeze, Itch, Rhinorrhoea and Nasal Blockage) 1-6 Hours Post Start of Allergen Challenge (2-7 Hours Post-dose) on Day 3 | On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. Nasal blockage, itch, sneeze and rhinorrhoea was scored on a categorical scale from 0 to 3 (0: no symptoms; 1: mild symptoms; 2: moderate symptoms; 3: severe symptoms). The total TNSS ranged from 0-12 point, with low score indicates well-being and higher score indicates more severity. Individual symptoms scores was summed at each time point (0, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340 and 360 minutes). The adjusted mean is provided as least square mean. | Day 3 of each treatment period (approximately up to 63 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weighted Mean of the Individual Components of TNSS (Sneeze, Itch, Rhinorrhoea and Nasal Blockage) 1-6 Hours Post Start of Allergen Challenge (2-7 Hours Post-dose) on Day 3 | On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. Nasal blockage, itch, sneeze and rhinorrhoea was scored on a categorical scale from 0 to 3 (0: no symptoms; 1: mild symptoms; 2: moderate symptoms; 3: severe symptoms). The total TNSS ranged from 0-12 point, with low score indicates well-being and higher score indicates more severity. Individual symptoms scores was summed to produce the TNSS at each time point (0, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340 and 360 minutes). The adjusted mean is provided as least square mean. | Day 3 of each treatment period (approximately up to 63 days) | 
| Weighted Mean Wet Tissue Weight (as a Surrogate Marker of Nasal Secretion) 1-6 Hours Post Start of Allergen Challenge (2-7 Hours Post-dose) on Day 3 | On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. Wet tissue weight assessments was measured as a surrogate marker of nasal secretion at 60, 120, 180, 240, 300 and 360 minutes. The adjusted mean is provided as least square mean. | Day 3 of each treatment period (approximately up to 63 days) | 
| Weighted Mean Nasal Congestion VAS 1-6 Hours Post Start of Allergen Challenge (2-7 Hours Post-dose) on Day 3 | On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. Nasal congestion was measured on 0-10 centimeter VAS scale (0: no symptoms and 10: the worst possible symptoms) with low score indicates well-being and higher values indicate greater congestion. It was measured at 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340 and 360 minutes. The adjusted mean is provided as least square mean. | Day 3 of each treatment period (approximately up to 63 days) | 
| Mean Forced Expiratory Volume in 1 Second (FEV1) | On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. FEV1 was measured at pre-challenge, 60, 120, 180, 240, 300 and 360 minutes. | Day 3 of each treatment period (approximately up to 63 days) | 
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or is associated with liver injury and impaired liver function defined as: alanine aminotransferase >=3 times upper limit of normal (ULN), and total bilirubin >=2 times ULN or international normalized ratio more than 1.5. | approximately up to 63 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proof of concept