Rhinitis
Conditions
Keywords
NAR, Capsaicin challenge
Brief summary
This study is designed to look at the affect of SB-705498 on rhinitis symptoms, as induced by capsaicin challenge
Interventions
DRUGPlacebo
SB-705498 placebo
DRUGSB-705498
12mg intranasal SB-705498
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| Change from baseline in peak nasal inspiratory flow (PNIF) after unilateral, incremental dose, intranasal challenge with capsaicin | 0-4hours following dosing |
| 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 |
| Heart rate | Day 1 |
| Assessment of Total Contralateral secretion's weight after unilateral, incremental dose, intranasal challenge with capsaicin | 0-4hours following dosing |
Countries
Netherlands
Outcome results
None listed