A Study To Assess The Effect Of SB-705498 In A Capsaicin Challenge Model

Study Overview
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Brief Summary
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This study is designed to look at the affect of SB-705498 on rhinitis symptoms, as induced by capsaicin challenge

Official Title
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A Randomised, Double-blind, Placebo-controlled Study to Assess the Effect of Oral, Single Dose SB-705498 in a Validated Intranasal Capsaicin Challenge Model in Healthy Volunteers

Conditions
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Rhinitis

Intervention / Treatment
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* Drug: SB-705498
* Drug: Placebo
* Other: Caspaicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy. Male or female between 18 and 60 years of age inclusive. Non-child bearing women or women of child bearing potential if they agree to use contraception as indicated by the protocol Non-smoker for at least 6 months with a pack history <5 pack years (Pack years = (No. of cigarettes smoked/day/20) x No. of years smoked). Body weight > 50 kg and body mass index (BMI) within the range 19 - 29.9 kg/m2 (inclusive). Capable of giving written informed consent. Available to complete all the required study measurements. Normal 12-lead ECG at screening. For Part 2 only: The subject must demonstrate reactivity to unilateral, intranasal challenge with the selected single dose of capsaicin, defined as development of TSS ≥ 3. Exclusion Criteria: Past medical history of rhinitis, including allergic, non-allergic rhinitis and rhinosinusitis. Nasal conditions likely to affect the outcome of the study, i.e. nasal septal perforation, nasal polyps, other nasal malformations. A history of gastrointestinal, hepatic, renal or multiple cardiovascular risk factors. Positive pre-study drug/alcohol screen. Positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. A positive test for human immunodeficiency virus (HIV) antibody (if determined by the local standard operating procedures (SOPs)). History of regular alcohol consumption within 6 months of the study. Exposure to more than four new chemical entities within 12 months prior to the start of the study. Participation in a clinical trial with a new molecule entity or any other clinical trial within 4 months of the start of the study. Use of prescription or non-prescription drugs, as well as of vitamins, herbal and dietary supplements (including St John's Wort) within 2 days prior to each study visit in Part 1 of the study or 14 days prior to the first treatment administration in Part 2 of the study. Inability to abstain from all intranasal or oral medication to treat nasal symptoms from the first capsaicin challenge to the completion of the study including: sodium cromoglycate, antihistamines, anticholinergics, alpha-adrenergic agonists and corticosteroids History of drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates their participation. Subjects demonstrating hypersensitivity to the placebo capsaicin challenge at baseline screening. Donation of blood or blood products in excess of 500mL within a 56 day period prior the start of Part 2 of this study. Pregnant females as determined by positive serum or urine human chorionic gonadotropin (hCG) test at screening or prior to dosing. Lactating females. Unwillingness or inability to follow the procedures outlined in the protocol. History of sensitivity to heparin or heparin-induced thrombocytopenia. Nicotine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. For Part 2 only: Subjects with known lactose intolerance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Placebo Comparator: PART 1-Visit 1-Placebo<br>Eligible subjects will receive matching placebo tablets | Drug: Placebo<br>* Subjects will be administered SB-705498 matching placebo tablets<br>|
| Experimental: PART 1-Visit 1-Capsaicin<br>Eligible subjects will receive incremental capsaicin doses | Other: Caspaicin<br>* Subjects will be challenged with 0.5 µg, 5.0 µg and 50 µg intranasal dose<br>|
| Placebo Comparator: PART 1-Visit 2-Placebo<br>Eligible subjects will receive matching placebo tablets | Drug: Placebo<br>* Subjects will be administered SB-705498 matching placebo tablets<br>|
| Experimental: PART 1-Visit 2-Capsaicin<br>Eligible subjects will receive maximum capsaicin dose | Other: Caspaicin<br>* Subjects will be challenged with 0.5 µg, 5.0 µg and 50 µg intranasal dose<br>|
| Placebo Comparator: PART 1-Visit 3-Placebo<br>Eligible subjects will receive matching placebo tablets | Drug: Placebo<br>* Subjects will be administered SB-705498 matching placebo tablets<br>|
| Experimental: PART 1-Visit 3-Capsaicin<br>Eligible subjects will receive matching placebo tablets incremental capsaicin doses | Other: Caspaicin<br>* Subjects will be challenged with 0.5 µg, 5.0 µg and 50 µg intranasal dose<br>|
| Placebo Comparator: PART 2-Visit 1-Placebo<br>Eligible subjects will receive matching placebo tablets | Drug: Placebo<br>* Subjects will be administered SB-705498 matching placebo tablets<br>|
| Experimental: PART 2-Visit 1-SB-705498<br>Eligible subjects will receive SB-705498 tablets | Drug: SB-705498<br>* Subjects will be administered a single dose of 400 mg SB-705498<br>|
| Experimental: PART 2-Visit 2-Capsaicin<br>Eligible subjects will receive matching placebo tablets incremental capsaicin doses | Other: Caspaicin<br>* Subjects will be challenged with 0.5 µg, 5.0 µg and 50 µg intranasal dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom scores and secretion weights |  | up to 83 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak nasal inspiratory flow changes after challenge |  | up to 83 days | 
| Biomarkers levels in the nasal samples |  | up to 83 days | 
| Blood levels of drug |  | up to 83 days | 
| Pharmacodynamic response |  | up to 83 days | 
| Safety parameters |  | up to 83 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Capsaicin challenge