Intranasal SB-705498 in Non-allergic Rhinitis Patients

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 Randomized, Double Blind, Placebo Controlled Study to Assessthe Effect of Intranasal Single Dose SB-705498 on the Response Tointranasal Capsaicin Challenge in Non-allergic Rhinitis Patients

Conditions
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Rhinitis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NAR patients 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. Subject must demonstrate reactivity to unilateral, intranasal challenge with the selected single dose of capsaicin, defined as development of TSS ≥ 3. Normal levels of total plasma IgG and negative allergy skin or Rast test to common aeorallergens. Good general health, apart from NAR, as determined by a responsible physician. Exclusion Criteria: Past medical history of allergic rhinitis or 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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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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm 1<br>3 incremental capsaicin doses | Drug: Placebo<br>* SB-705498 placebo<br>|
| Active Comparator: Arm 2<br>3 incremental capsaicin doses | Drug: SB-705498<br>* 12mg intranasal SB-705498<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of total symptom score (TSS) after unilateral, incremental dose, intranasal challenge with capsaicin |  | 0-4hours following dosing | 
| Assessment of total Ipsilateral secretion's weight after unilateral, incremental dose, intranasal challenge with capsaicin |  | 0-4hours following dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in peak nasal inspiratory flow (PNIF) after unilateral, incremental dose, intranasal challenge with capsaicin |  | 0-4hours following dosing | 
| Assessment of Total Contralateral secretion's weight after unilateral, incremental dose, intranasal challenge with capsaicin |  | 0-4hours following dosing | 
| Number of participants with Individual Symptoms as assessed by TSS components after unilateral, incremental dose, intranasal challenge with capsaicin |  | 0-4hours | 
| Soluble biochemical mediators, including but not limited to neuropeptides, in nasal secretions induced after unilateral, incremental dose, intranasal challenge with capsaicin |  | 0-4hours following dosing | 
| Intranasal, single dose SB-705498 plasma PK parameters-Cmax |  | 0-4hours | 
| Intranasal, single dose SB-705498 plasma PK parameters- Tmax |  | 0-4hours post dosing | 
| Intranasal, single dose SB-705498 plasma PK parameters- AUC(0-t) |  | 0-4hours post dosing | 
| Number of participants with adverse events |  | Day 1 | 
| Number of participants with vital signs data outside range of potential clinical importance- Systolic blood pressure (SBP) and diastolic blood pressure (DBP) |  | Day 1 | 
| Heart rate |  | Day 1 | 
| Number of participants with nasal examination data |  | Day 1 | 
| Number of participants with abnormal ECG findings |  | Day 1 | 
| Body temperature |  | Day 1 | 
| Number of participants with abnormal hematology values |  | Day 1 | 
| Number of participants with abnormal clinical chemistry values- Carbon dioxide content/Bicarbonate, Cholesterol, Potassium, Triglycerides |  | Day 1 | 
| Number of participants with abnormal clinical chemistry values- Creatinine |  | Day 1 | 
| Number of participants with abnormal clinical chemistry values- Gamma Glutamyl Transferase, Lactate Dehydrogenase |  | Day 1 | 

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